multifaceted approach to literature review

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Cervicogenic Headaches: A Literature Review and Proposed Multifaceted Approach to Diagnosis and Management

Affiliations.

1 Department of Pediatrics, Section of Neurology and Developmental Neuroscience, Baylor College of Medicine at Texas Children's Hospital, 7200 Cambridge Street, 9th Floor, Houston, TX 77030, USA.
2 Department of Neurology, Baylor College of Medicine, 7200 Cambridge Street, 9th Floor, Houston, TX 77030, USA.
3 Department of Neurology, Baylor College of Medicine, 7200 Cambridge Street, 9th Floor, Houston, TX 77030, USA. Electronic address: [email protected].
PMID: 38575265
DOI: 10.1016/j.ncl.2023.12.008

Cervicogenic headaches are a secondary headache disorder attributable to cervical spine dysfunction resulting in head pain with or without neck pain. Diagnosis of this condition has been complicated by varied clinical presentations, causations, and differing diagnostic criteria. In this article, we aim to clarify the approach to diagnosing cervicogenic headaches by providing an overview of cervicogenic headaches, clinical case examples, and a practical diagnostic algorithm based on the most current criteria. A standardized approach will aid in confirmation of the diagnosis of cervicogenic headaches and facilitate further research into this condition.

Keywords: Cervicogenic headaches; Neck pain; Secondary headaches.

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Systematic review
Open access
Published: 20 September 2016

Effectiveness of multifaceted implementation strategies for the implementation of back and neck pain guidelines in health care: a systematic review

Arnela Suman ORCID: orcid.org/0000-0003-0656-490X 1 ,
Marije F. Dikkers 2 ,
Frederieke G. Schaafsma 1 , 3 ,
Maurits W. van Tulder 2 &
Johannes R. Anema 1 , 3

Implementation Science volume 11 , Article number: 126 ( 2015 ) Cite this article

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For the optimal use of clinical guidelines in daily practice, mere distribution of guidelines and materials is not enough, and active implementation is needed. This review investigated the effectiveness of multifaceted implementation strategies compared to minimal, single, or no implementation strategy for the implementation of non-specific low back and/or neck pain guidelines in health care.

The following electronic databases were searched from inception to June 1, 2015: MEDLINE, Embase, PsycInfo, the Cochrane Library, and CINAHL. The search strategy was restricted to low back pain, neck pain, and implementation research. Studies were included if their design was a randomized controlled trial, reporting on patients (age ≥18 years) with non-specific low back pain or neck pain (with or without radiating pain). Trials were eligible if they reported patient outcomes, measures of healthcare professional behaviour, and/or outcomes on healthcare level. The primary outcome was professional behaviour. Guidelines that were evaluated in the studies had to be implemented in a healthcare setting. No language restrictions were applied, and studies had to be published full-text in peer-reviewed journals, thus excluding abstract only publications, conference abstracts, and dissertation articles. Two researchers independently screened titles and abstract, extracted data from included studies, and performed risk of bias assessments.

After removal of duplicates, the search resulted in 4750 abstracts to be screened. Of 43 full-text articles assessed for eligibility, 12 were included in this review, reporting on 9 individual studies, and separate cost-effectiveness analyses of 3 included studies. Implementation strategies varied between studies. Meta-analyses did not reveal any differences in effect between multifaceted strategies and controls.

This review showed that multifaceted strategies for the implementation of neck and/or back pain guidelines in health care do not significantly improve professional behaviour outcomes. No effects on patient outcomes or cost of care could be found. More research is necessary to determine whether multifaceted implementation strategies are conducted as planned and whether these strategies are effective in changing professional behaviour and thereby clinical practice.

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Introduction

The recent Global Burden of Disease Study showed that low back pain (LBP), with 83 million years lived with disability, is the leading cause of disability worldwide, while neck pain (NP) is ranked 4th with 33.6 million years lived with disability [ 1 – 3 ]. To assist healthcare professionals in providing best-evidence care for LBP and NP, many guidelines for these health problems have been developed [ 4 , 5 ]. Clinical practice guidelines are defined by the Institute of Medicine as ‘statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options, and are aimed at improving healthcare quality and outcomes’ [ 6 ]. Most of the guidelines for LBP/NP are developed for multidisciplinary use in primary care and are mainly national professional guidelines. The contents of these guidelines are similar. For example, the guidelines encourage similar diagnostic triages and discourage the use of diagnostic imaging, bed rest, and referrals to specialist care unless neurological or pathological causes are suspected [ 4 ]. The use of these guidelines might improve the quality of care for patients with LBP/NP and reduce the financial and societal burden of these disorders.

For the optimal use of guidelines in clinical practice, mere distribution of the guideline and information materials among healthcare professionals is not enough and active implementation is a necessity [ 7 ]. Many studies have been conducted to investigate the effectiveness of implementation strategies. For example, the Effective Practice and Organisation of Care (EPOC) Group of the Cochrane Collaboration has published several systematic reviews on this topic. The results of various implementation strategies, such as the use of educational meetings and workshops, educational outreach, and audit and feedback have shown small effects on improvement of professional practice (6 % improvement for educational meetings and outreach and 5 % for audit and feedback) [ 8 – 10 ]. In line with these findings, Grol and Wensing argued that the simultaneous use of several implementation strategies, i.e. a multifaceted or multicomponent approach to implementation is most effective in successfully implementing guidelines and thus changing practice [ 7 ]. However, a recent overview of systematic reviews of multifaceted implementation strategies by Squires et al. suggested that these strategies may not be more effective than single-component interventions [ 11 ].

As no studies up to now specifically reviewed the effect of multifaceted implementation strategies for the implementation of non-specific LBP/NP guidelines, the current systematic review will address the following research question: ‘What is the effectiveness of multifaceted implementation strategies compared to minimal, single or no implementation strategy for the implementation of non-specific low back and/or neck pain guidelines in health care?’ Outcomes on healthcare professional behaviour (e.g. referral for diagnostic imaging), and patient health (e.g. quality of life) will be assessed to measure adherence to the guidelines and thereby the success of the implementation process.

Material and methods

Eligibility criteria.

For the purpose of this review, multifaceted strategies were defined as interventions that consist of a combination of two or more elements from the implementation strategy taxonomy of the EPOC classification system [ 12 ]. As this review aimed to assess the effectiveness of implementation strategies, studies were considered for this review if their design was a randomized controlled trial (RCT), involving either individual or cluster randomization and including a control group that received a minimal, single, or no implementation strategy. Studies were eligible if reporting on patients of either gender (age ≥18 years) with non-specific LBP or NP (with or without radiating pain) of any duration. Studies of LBP or NP caused by infection, cauda equina syndrome, bone rarefaction, compression fracture of a vertebral body, tumour, or fibromyalgia were excluded. Cost-effectiveness analyses of included trials were also included. Trials were eligible if they reported measures of healthcare professional behaviour (the primary outcome for this review, patient outcomes, and/or outcomes on healthcare level). Guidelines that were evaluated in the studies had to be implemented in a healthcare setting (i.e. a setting where individual health care is provided to a patient), for example, primary care (general practitioner (GP) or physiotherapist (PT)), occupational health care, or secondary (hospital) care. Guidelines for healthcare insurance were therefore excluded. No language restrictions were applied, and studies had to be published full-text in peer-reviewed journals, thus excluding abstract only publications, conference abstracts, and dissertation articles.

Information sources

The following electronic databases were searched until June 1, 2015: MEDLINE (PubMed), Embase, PsycInfo, the Cochrane Library, and CINAHL (Ebsco). In close collaboration with a medical information specialist, a broad search was performed with only two restrictions: LBP and/or NP and implementation. Full electronic search strategies for all five databases are presented in Additional file 1 : Appendix A. In cases of ambiguity, or where full-text publications of selected abstracts could not be found, authors of the respective studies were contacted. The reference lists of all included studies were screened to identify additional studies.

Study selection and data extraction

After removal of duplicate results, two reviewers (AS and MD) independently reviewed all titles and abstracts identified by the electronic search. Subsequently, the reviewers engaged in a consensus method to eliminate discrepancies in the selection process. In cases where the reviewers could not come to consensus regarding study eligibility, a third reviewer (FGS or MWvT) was consulted. Full-text articles of studies were obtained when the study was deemed to meet the inclusion criteria or in cases where perusal of title and abstract did not provide sufficient information to assess eligibility of the study. Both reviewers independently screened all selected full-text articles for definitive eligibility, and the same consensus protocol was followed as for the screening of titles and abstracts. Using an adapted form of the ‘Good practice data extraction form’ of the EPOC group, study characteristics and relevant data of all included studies were independently extracted by the two reviewers (AS and MD). Results were discussed in order to reach consensus and assure correct interpretation of the studies. In cases where consensus could not be reached, a third reviewer (FGS) was consulted.

Assessment of risk of bias of studies

The risk of bias of the included randomized trials was evaluated by two review authors independently (AS and MD), using the Cochrane Collaboration’s tool for assessing risk of bias and the suggested risk of bias criteria for EPOC reviews [ 13 , 14 ]. Disagreements were resolved by consensus. The quality of the economic evaluations was not assessed, because this was outside the scope of the current review. The following criteria were assessed for high, unclear or low risk of bias for every study: random sequence generation (selection bias); allocation concealment (selection bias); similarity of baseline characteristics and outcome measurements; follow-up; blinding of participants and personnel (performance bias); blinding of outcome assessment (detection bias); protection against contamination; incomplete outcome data (attrition bias); selective outcome reporting (reporting bias); and other bias.

Studies that had a low risk of bias score on at least six criteria were judged to be low risk of bias studies [ 15 ]. Studies that had five or less low risk of bias scores were judged to be high risk of bias studies.

Two review authors (AS and MD) independently assessed the overall quality of the evidence for all pooled outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach [ 16 – 19 ]. The GRADE approach specifies four levels of quality. High-quality rating is for randomized controlled evidence, and the quality rating can be downgraded if limitations in one or more of the following domains are encountered: Study limitations encountered in ‘risk of bias’ assessment of study; consistency of study (i.e. the similarity of estimates of treatment effects for the outcome across studies); directness of the study (i.e. the extent to which the participants, interventions, and outcomes in the studies were comparable to those defined in the inclusion criteria of this review); precision of the study (i.e. the degree of certainty surrounding an effect estimate); and publication bias (i.e. the probability of selective publication of studies and outcomes).

The overall quality of the evidence for each pooled outcome was the result of the combination of all domains and leads to four levels of evidence [ 18 ]:

High-quality evidence: Further research is very unlikely to change the confidence in the estimate of effect.

Moderate-quality evidence: Further research is likely to have an impact on the confidence in the estimate of effect and may change the estimate.

Low-quality evidence: Further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimate.

Very low-quality evidence: Any estimate of effect is very uncertain.

Data extraction

Two independent reviewers (AS and MD) extracted data from the included studies using the EPOC data collection checklist and data extraction template [ 12 ]. The data extraction form was the first pilot tested using one of the included studies. Disagreements in data extraction were resolved by consensus. The following data were extracted:

Bibliographic data (authors, title study, journal, and date of publication)

Study characteristics (study type and design, unit of allocation, duration of follow-up)

Participant characteristics (population description (e.g. (neck or back pain) patients or (type of) professionals), total number of participants randomized, mean age, gender, severity of illness, co-morbidities)

Setting characteristics (location, social context, clusters, withdrawals, and exclusions)

Description of intervention and control groups (content, dose, components, duration, timing, delivery, providers, number randomized to group, theory base)

Outcomes assessed (outcome definitions, time points measured and reported, unit of measurement, outcome tool, scales, missing data)

Study results (baseline data, comparison, outcome, subgroup, time points, results intervention and comparison)

Synthesis of results

The included studies first were categorized into types of interventions (according to the EPOC taxonomy) and types of outcome measures. Meta-analyses were separately planned and conducted for the comparison of multifaceted implementation strategies vs. controls (i.e. usual care or minimal implementation) for various outcomes. Outcomes on healthcare professional behaviour were considered indicators for guideline adherence and thus the primary outcome for success of guideline implementation. The effects on professional behaviour were categorized into ‘treatment’ and ‘referral’ behaviour outcome groups. In the treatment group, outcomes on treatment behaviour were classified into adequate patient information, advising active treatment, and prescribing medication. Outcomes on referral behaviour were separately analysed for referrals for X-ray, computed tomography (CT), or magnetic resonance imaging (MRI) scans, physical therapy, and speciality/secondary care referrals. Additional file 2 : Appendix C shows the data sources and calculations used for the meta-analyses.

To calculate effects, the data for the pooled outcomes of each study were entered into Review Manager (RevMan) 5.3 software. All pooled outcome data were dichotomous or dichotomized, and for all outcomes, odds ratios (using random effects models) and 95 % CIs were calculated in RevMan to estimate the implementation effects. To determine the presence of heterogeneity, I 2 was analysed in RevMan. When I 2 was more than 50 %, the studies were judged to be heterogeneous.

Identification and selection of studies

The electronic search resulted in 8255 references, of which 2476 were retrieved from MEDLINE, 4181 from Embase, 876 from CINAHL, 293 from Cochrane, and 429 from PsycInfo. After removing duplicates, titles and abstracts of 4750 records were screened. Of 43 records, full-text articles were screened for eligibility. Twelve articles were included in the current review (see Additional file 3 : Table S1) [ 20 – 31 ], and 31 articles were excluded (see Additional file 4 : Table S2) [ 32 – 62 ]. Figure 1 shows a flow chart of the inclusion process, including reasons for exclusion (several exclusion reasons per article possible) of records. Screening of reference lists of the included articles did not result in any additional inclusions.

Flowchart of inclusion process

The 12 included articles were based on 8 individual studies, of which 4 based their implementation strategy on theory and described the development of their strategy. Three studies separately reported cost-effectiveness analyses, and 1 study described outcomes on patient and professional levels in 2 separate articles. One study was targeted at patients with a whiplash, while all other studies were on non-specific LBP. Additional file 5 : Table S3 provides a summary of the included studies and their characteristics. A great variety of intervention elements was applied across the studies, and several outcomes were measured. The guidelines implemented in the included studies had similar objectives such as encouraging activation, restoration of normal functioning, and exercise, while discouraging referrals for secondary care and diagnostic imaging. Additional file 6 : Appendix B lists the excluded full-text articles with reasons for their exclusion.

In Additional file 7 : Table S4, intervention elements according to the EPOC taxonomy are shown for the included studies. Nine types of elements could be identified. Next to the obvious dissemination of clinical practice guidelines, educational material and educational meetings were the most commonly applied elements. Local opinion leaders, audit and feedback, reminders, and organizational interventions were not used as often, and only three studies applied a patient-mediated intervention element. The implementation strategies of most studies consisted of four to five intervention elements. Additional file 8 : Table S5 shows the types of outcomes that were measured in the included studies. Most studies measured physician treatment adherence to guideline recommendations and the number of referrals to secondary care, medical diagnostics, and/or physical therapy. Only three studies reported outcomes on patient level.

Quality of included studies

Figure 2 shows the risk of bias judgement of the included randomized trials. With only two studies [ 25 , 28 ] judged to have a high risk of bias according to the predefined cut-off point, overall quality of the included studies was good. Blinding of participants and personnel (performance bias) was judged to be a source of high risk of bias in all but two studies [ 22 , 30 ]. Other sources of bias like a follow-up of at least 80 %, blinding of outcome assessment, and selective reporting were considered a risk of bias in a few studies only. For four of the nine studies, the risk of bias based on similarity of baseline outcome measurements was unclear. Additional file 9 : Table S6 shows the summary of findings table, including the assessment of the quality of the evidence using the GRADE system.

Risk of bias for included studies

Effect on professional behaviour

Referral behaviour.

Figures 3 , 4 , 5 , and 6 show that multifaceted implementation is not more effective than usual care or minimal implementation in improving guideline concordant referral behaviour. The statistical heterogeneity of the pooled studies is high.

Pooled analysis for referral rates for X-rays (moderate-quality evidence)

Pooled analysis for referral rates for CT/MRI scans (low-quality evidence)

Pooled analysis for referral rates for physiotherapy (very low-quality evidence)

Pooled analysis for referral rates for secondary/specialty care (very low-quality evidence)

Treatment behaviour

Figures 7 , 8 , and 9 show that there is no statistically significant difference between multifaceted implementation and usual care or minimal implementation in providing adequate patient information and prescribing medication. However, active treatment was more often advised in the multifaceted implementation groups than in the control groups (Fig. 9 , OR 0.69; 95 % CI 0.48 to 0.99).

Pooled analysis for the provision of adequate patient information (low-quality evidence)

Pooled analysis for medication prescription (low-quality evidence)

Pooled analysis for advising active treatment (low-quality evidence)

Effect on patient outcomes

Additional file 10 : Table S7 shows the results for patient outcomes at 12-month follow-up. Three studies reported outcomes on patient level [ 20 , 23 , 30 ]. The most common patient outcomes measured were functional capacity or disability, days of sick leave, and quality of life (QoL). No significant differences on 12-month follow-up were found for any of these outcomes.

Effect on cost of care

Three studies performed and separately reported a cost-effectiveness analysis for their implementation strategies [ 21 , 24 , 29 ]. Two of these cost-effectiveness analyses [ 21 , 29 ] showed that multifaceted implementation yielded lower costs and more effects, although these results were not statistically significant. The third study showed no cost or effect advantages for the intervention group compared to the control group.

This review showed that multifaceted strategies for the implementation of neck and/or back pain guidelines in health care do not significantly improve professional behaviour outcomes. Only active treatment was more often advised in the multifaceted implementation groups than in the control groups. No effects on patient outcomes or cost of care could be found. These results are not in line with findings from previous research in other fields that showed that active, multifaceted implementation strategies are effective in changing professional behaviour [ 63 – 69 ] compared to passive dissemination of guidelines or minimal implementation activities. However, the results are in line with a more recent and more elaborate overview of systematic reviews, which suggested that multifaceted implementation strategies are not more effective than other strategies [ 11 ].

Few studies that were found in the electronic database search were included in the current review. Many studies were excluded because their interpretations of ‘multifaceted’ strategies were not in line with the EPOC definition. For example, several studies indicated having applied a multifaceted approach by organizing several workshops on multiple occasions. However, all workshops were part of one element, i.e. educational meetings. As according to the EPOC taxonomy, an intervention is multifaceted if it applies two or more elements [ 12 ], these strategies did not meet the criteria for being multifaceted. It seems that either the EPOC taxonomy is not often used or the definition of multifaceted strategies is open to interpretation. Either way, consensus on the definition of multifaceted and application of the taxonomy could improve insight into the effectiveness of multifaceted implementation strategies.

Only 12 articles were identified and included in this study. These studies were not able to produce high-quality evidence for changes on professional or patient outcomes in the current review. Only 3 articles reported cost-effectiveness analyses of original studies. These cost-effectiveness studies were evaluated by a recent review by Jensen et al., who showed that the quality of these economic evaluations was moderate and that the studies, although similar to one another, showed conflicting results on cost-effectiveness [ 70 ]. It is advisable that researchers implementing guidelines also include cost-effectiveness in their analyses. Multifaceted implementation strategies can be costly, especially when they are applied to implement guidelines on a national level. The efforts and resources for applying these strategies are only worthwhile if they are effective in improving patient outcomes or quality of care. If these strategies also lead to changes in specific professional behaviour, e.g. less unnecessary healthcare utilization referrals or medication prescriptions, and advises to return-to-work, the costs of implementation might be offset by the decrease in costs of care.

Of the included studies, only 3 applied a patient-mediated implementation element. Of these 3 studies, only 1 actually measured patient outcomes (20). Two other studies reported patient outcomes, while they had not applied patient-mediated elements. This might be an explanation for the lack of effect on patient outcomes. Grol and Wensing [ 7 ] identified several patient characteristics as possible factors for implementation success. For example, patient attitude and knowledge might pose a barrier for the uptake of changes by professionals. Therefore, when aiming to improve professional practice, applying elements that are targeted at patient-mediated barriers and facilitators might be essential to guideline implementation. This is underlined by the slightly more positive results in the study of Becker et al. [ 20 ] compared to the other studies that reported patient outcomes. However, merely applying patient-mediated interventions does not necessarily address patient barriers. It is advisable that these barriers be taken into account when designing implementation strategies.

Regarding the effectiveness of more comprehensive strategies compared to strategies that apply fewer elements, the results from the current review are inconclusive. It seems that more does not always mean better, and multifaceted strategies possibly are only more effective when they apply different elements that are targeted at various barriers and facilitators for change [ 71 ]. However, this was not confirmed in our review. A recent review by Mesner et al. suggested that the success of implementation interventions does not necessarily depend on the specific type of interventions but rather might be determined by the increase of frequency and duration of implementation interventions [ 72 ]. There is still a lack of the use of theory in implementation research, and studies on guideline implementation strategies poorly justify the choice of intervention [ 72 , 73 ]. This is in line with the findings of the current review, in which only four studies (partly) based their strategies on theories and also reported on the development of their strategy. This could be one possible explanation for the lack of effective results in these studies [ 73 ]. However, for many studies, it is unknown whether the implementation strategies were conducted as planned, which might be another factor influencing the effectiveness of the implementation strategies. Process evaluations are necessary to gain more insight into this factor; however, of the included studies in this review, only one study performed a process evaluation [ 28 ] and reported moderate to high levels of fidelity [ 74 ].

Strengths and limitations of this study

When interpreting the results of the current review, some limitations should be taken into account. Firstly, this review did not search for unpublished studies. Also, due to the amount of synonyms for the term ‘Implementation’ included in the search strategy, it might be possible that some studies were missed during the search phase. Furthermore, all but two studies were published before 2007, and the quality of the evidence found in these studies was very low to moderate, according to the GRADE assessment performed in the current review. Another important limitation is the comparability of the studies. Not only did the studies apply various implementation strategies, usual dissemination in the control groups also varied. Besides, there was a wide variation in the outcomes that were measured, how they were measured, and how they were reported. In the meta-analyses, the statistical heterogeneity was large, and results should therefore be interpreted with caution. For example, one study where the control group did not receive any implementation strategy was compared with a study in which the control group received a patient-mediated implementation strategy. Other reasons for heterogeneity might be clinical (e.g. due to different settings and patients) or statistical (e.g. different study sizes). No sensitivity analyses were performed due to the small number of studies that could be included in the meta-analyses, and notwithstanding the high statistical heterogeneity found in these analyses as expressed by the I 2 measures, these analyses might give an insight into the effect directions of the included studies.

By following the method guidelines for systematic reviews as posed by the Cochrane Back Review Group [ 75 ], and the Cochrane Handbook for Systematic Reviews of Interventions [ 12 ], the current review pursued the highest methodological quality. By applying a broad and comprehensive search strategy and supplementary hand search of reference lists of included studies, this review ensured that as few as possible, eligible studies were missed. To further minimize this chance, no language restrictions were applied during the inclusion and data collection phases.

Abbreviations

Cost-effectiveness analysis

Computed tomography

Effective Practice and Organisation of Care

General practitioner

Low back pain

Magnetic resonance imaging

Nurse practitioners

Physician assistants

Physiotherapist

Quality of life

Randomized controlled trial

Röntgen radiation imaging

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Acknowledgements

The authors thank Linda Schoonmade, a medical information specialist at the VU University medical centre Amsterdam, for her assistance in the development of the search strategy.

This systematic review was part of a project funded by The Netherlands Organisation for Health Research and Development (ZonMw).

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All authors collaborated in conceiving this study. AS and MD screened citations and full-text articles and extracted, analysed, and interpreted the data. AS wrote the initial manuscript for this study. All authors were involved in the interpretation of the data and critical revision of the manuscript. All authors read and approved the final manuscript.

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Additional files

Additional file 1:.

Appendix A. Full electronic database searches. (DOCX 14 kb)

Additional file 2:

Appendix C. Data sources and calculations for meta-analyses. (DOCX 15 kb)

Additional file 3: Table S1.

References to included studies. (DOCX 15 kb)

Additional file 4: Table S2.

References to excluded full-text studies. (DOCX 17 kb)

Additional file 5: Table S3.

Characteristics of included studies. (DOCX 23 kb)

Additional file 6:

Appendix B. List of excluded studies and reasons for exclusion. (DOCX 17 kb)

Additional file 7: Table S4.

Interventions of included studies according to EPOC taxonomy (all on professional level unless stated otherwise). (DOCX 15 kb)

Additional file 8: Table S5.

Grouped outcome measures of included studies (all on professional level unless stated otherwise). (DOCX 14 kb)

Additional file 9: Table S6.

Summary of findings. (DOCX 17 kb)

Additional file 10: Table S7.

Patient outcomes at 12-month follow-up. (DOCX 14 kb)

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Suman, A., Dikkers, M.F., Schaafsma, F.G. et al. Effectiveness of multifaceted implementation strategies for the implementation of back and neck pain guidelines in health care: a systematic review. Implementation Sci 11 , 126 (2015). https://doi.org/10.1186/s13012-016-0482-7

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Objective : We aimed to explore the multifaceted etiology of recurrent implantation failure (RIF) and evaluate the efficacy of various management strategies, with a focus on refining examination protocols and treatment pathways to improve implantation success rates in patients undergoing in vitro fertilization-embryo transfer. Mechanism : The development of RIF can be attributed to a complex causal network of factors. Chromosomal anomalies, such as aneuploidies, directly impact the genetic viability of embryos. Immune system dysregulation, marked by the presence of autoantibodies, disrupts the normal immunological tolerance required for successful implantation. Endocrine disruptions interfere with the hormonal balance essential for preparing the endometrium for implantation. Anatomical irregularities in the female reproductive tract can physically impede the embryo’s ability to implant. Lifestyle factors, including diet, stress, and environmental exposures, influence both male and female reproductive health, affecting gamete quality and implantation potential. These diverse factors interact in a multifaceted manner, making a personalized diagnostic and therapeutic approach essential for addressing the specific causes in each case of RIF. Findings in brief : The review synthesizes current understanding of RIF’s etiology, highlighting the need for innovative interventions and adjustments in clinical practice. It emphasizes the significance of a highly personalized approach in managing RIF, incorporating refined examination protocols and tailor-made treatment pathways to address the unique combination of factors present in each case. Conclusions : Effective management of RIF requires innovative interventions and a shift in clinical practice towards personalized care. Identifying gaps in the current understanding of RIF points towards a clear direction for future research, aimed at refining treatment protocols and improving outcomes for patients. This contributes significantly to the broader field of reproductive medicine, aiming to alleviate the clinical and psychological burdens of RIF.

Recurrent implantation failure (RIF) is a significant impediment to achieving successful conception for couples undergoing assisted reproductive technology (ART), affecting roughly 10% of in vitro fertilization-embryo transfer (IVF-ET) patients globally [ 1 ]. This condition not only presents clinical challenges but also imposes substantial emotional and financial stress on affected individuals. The complexity of RIF is broad and multifaceted, with its etiology not fully understood, highlighting the urgent need for ongoing research to explore its underlying causes and develop effective treatment strategies.

The definition of RIF has evolved in response to advancements in in vitro fertilization (IVF) technology and clinical understanding. Historically, RIF was defined by the number of unsuccessful IVF cycles or the number of high-quality embryos transferred without resulting in pregnancy [ 2 ]. However, the shift towards single embryo transfer practice to reduce multiple gestation risks has necessitated a reevaluation of RIF criteria. In 2023, the Chinese expert consensus introduced a refined definition that considers both the quantity and the quality, including the developmental potential of transferred embryos [ 3 ]. This redefinition reflects the dynamic nature of ART, where evolving technological and clinical insights require adaptable definitions.

Adding to the complexity of defining RIF, major reproductive health organizations such as the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) have established their criteria. ESHRE’s guidelines suggest defining RIF as a condition observable only in IVF patients, characterized by a series of embryo transfers deemed viable failing to result in a positive pregnancy test often enough to warrant further investigation and/or interventions [ 4 ]. A key aspect of their recommendation is the adoption of a cumulative predicted chance of implantation greater than 60% as a threshold for initiating further investigation and treatment options. This nuanced approach by ESHRE underscores the importance of individualized care and the necessity for definitions to evolve with technological and clinical advancements.

Understanding the etiology of RIF is crucial for developing personalized treatment strategies. Factors such as immune system anomalies, thrombotic processes, endometrial receptivity, anatomical abnormalities in the reproductive tract, infections, and hormonal imbalances all contribute to the condition. The collective impact of these factors adds to the overall complexity of RIF, necessitating individualized diagnostic and therapeutic approaches.

This review endeavors to explore the complex etiology of RIF, drawing on the latest research and the guidelines provided by ESHRE and ASRM. It aims to synthesize current understandings and management strategies, emphasizing the need for personalized treatment plans. By presenting a detailed examination of RIF’s multifaceted aspects and the varied effectiveness of treatment approaches, this paper contributes to the ongoing dialogue on optimizing care for individuals grappling with RIF, setting the stage for future research directions and clinical application.

The narrative review meticulously identifies and selects relevant literature using a method that is both thorough and aligned with scientific principles, ensuring the transparency and reproducibility of findings. We conducted an exhaustive literature search across a variety of databases to encompass a wide range of studies pertinent to RIF.

The databases searched include PubMed, MEDLINE, Embase, the Cochrane Library, Google Scholar, Web of Science, and key Chinese databases such as CNKI, Wanfang, and Weipu Database, with the literature search through December 2023. Our search strategy employed a combination of Medical Subject Headings (MeSH) and free-text term variants to ensure comprehensive coverage of the topic.

Additional search terms covered areas related to fertility treatments and outcomes, such as “embryo transfer”, “fertility”, “infertility”, “assisted reproductive technology”, “pregnancy”, “miscarriage”, “implantation”, “intracytoplasmic sperm injection (ICSI)”, and “ in vitro fertilization”. This extensive and detailed search strategy was designed to be inclusive, and not restricted by language, publication status, or study design. The aim was to provide a comprehensive overview of current knowledge and emerging insights into managing RIF. Moreover, a manual review of reference lists from identified articles was also conducted to ensure no significant study was overlooked, further broadening the scope of our literature review.

Inclusion criteria were established to identify studies that specifically address the multifaceted approaches to managing RIF, including clinical research, reviews, and guidelines that contribute significantly to understanding and treating this condition. Exclusion criteria were applied to omit studies that did not directly relate to RIF, were not within the scope of reproductive medicine, or lacked substantial evidence or relevance to the review’s focus areas.

This methodological approach enhances the credibility of our narrative review by providing a clear, reproducible framework for literature selection and analysis. It underscores our commitment to a thorough examination of the multifaceted approaches to managing RIF, contributing valuable insights and innovations to the field.

The endometrium, as the site for embryonic development, is regulated by steroid hormones, notably estrogen and progesterone. These hormones are essential in controlling the growth and differentiation of the endometrium, making the endocrine balance critical for successful embryo implantation.

Progesterone is key in embryo implantation. Studies have shown that patients with RIF have significantly lower progesterone levels during early pregnancy compared to those with normal pregnancies [ 5 ]. However, the link between luteal phase defects and implantation failure remains to be conclusively established, highlighting the need for further research in this area. There is debate over the effect of elevated estradiol levels during the artificial preparation of frozen embryo transfer on luteal transformation and embryo implantation, but studies suggest that neither normal nor increased estradiol levels significantly alter the process [ 6 ].

Polycystic ovary syndrome (PCOS) patients often exhibit insulin resistance and metabolic abnormalities, including altered blood lipid and glucose levels, which can hinder embryo implantation [ 7 ]. Concurrent thyroid dysfunction is also observed in patients with RIF [ 8 , 9 ].

Chromosomal abnormalities in embryos, such as translocations, inversions, insertions, and deletions, are significant contributors to implantation and pregnancy failure. Although more common in RIF patients than in the general population, the incidence of such abnormalities is about 2%, with translocations being the most frequent [ 10 , 11 ]. The incidence of chromosomal abnormalities in embryos increases with age; reports indicate that up to 76% of early pregnancy spontaneous miscarriages are due to these abnormalities [ 12 ]. It is recommended to perform high-resolution chromosomal karyotyping analysis and provide genetic counseling for both partners in RIF cases.

Successful embryo implantation is crucially dependent on the synchronization of the embryo with the uterine endometrium’s development, specifically during the optimal “implantation window”. Studies demonstrate that approximately 66% of RIF patients experience impaired endometrial receptivity and altered interactions between the embryo and endometrium [ 13 ]. Transcriptomic analyses have revealed distinct expression profiles in about 25% of RIF patients, varying throughout the menstrual cycle and potentially affecting the implantation window’s timing [ 14 , 15 ]. Furthermore, dysregulation in prostaglandin synthesis may contribute to decreased endometrial receptivity in these patients [ 16 ].

The methods used for assessing endometrial receptivity, such as endometrial biopsy and the endometrial receptivity array (ERA), are still under active research. Although endometrial biopsy aids in determining the optimal implantation period, its practicality is restricted due to invasiveness, the delay in results, and its inapplicability during embryo transfer cycles.

Anatomical abnormalities within the reproductive system, including Müllerian duct anomalies, uterine fibroids, adenomyosis, endometrial polyps, intrauterine adhesions, and hydrosalpinx, have significant implications for IVF outcomes [ 17 ]. For patients with RIF, the presence of uterine anomalies such as septate or bicornuate uterus should be carefully evaluated. Both partial and complete septate uteri are linked to reduced fertility outcomes, including lower pregnancy rates and increased risks of early miscarriage and preterm birth [ 18 ]. Similarly, a bicornuate uterus is associated with higher risks of preterm birth and mid-trimester miscarriage.

Uterine fibroids can lead to deformation of the uterine cavity and adhesions, hindering embryo implantation. Particularly, submucosal fibroids have been found to significantly affect IVF outcomes by impacting implantation and pregnancy rates through various mechanisms, such as increased uterine muscle contractions, abnormal blood vessel formation, and changes in the endocrine environment within the uterine cavity [ 19 ]. However, the influence of intramural and subserosal fibroids is relatively minor [ 20 ].

Adenomyosis, characterized by an abnormal immune response due to altered sex steroid levels, negatively impacts implantation success [ 21 ]. Elevated levels of pro-inflammatory cytokines and increased anti-inflammatory mediators have been observed in patients with adenomyosis, along with a decrease in uterine natural killer (uNK) cell functionality, which is also observed in endometriosis and linked to reduced implantation success [ 22 ]. Endometrial polyps and intrauterine adhesions, often resulting from procedures such as uterine curettage, can obstruct embryo implantation by causing uterine cavity deformities and endometrial damage [ 23 , 24 , 25 ]. Furthermore, hydrosalpinx may compromise IVF-ET outcomes due to factors such as insufficient nutrient supply and the presence of inflammatory agents [ 26 ].

The female reproductive tract is home to distinct bacterial populations, extending from the vagina to the ovaries [ 27 ]. The role of the female reproductive tract’s microbiome is also pivotal, with the vaginal microbiota, particularly lactic acid bacteria such as Lactobacillus crispatus , L. jensenii , L. iners , and L. gasseri , showing a positive correlation with pregnancy outcomes [ 28 ]. A decrease in vaginal lactobacillus and increased microbial alpha diversity have been noted in unexplained RIF patients, contrasting with those who achieved pregnancy after a thaw cycle transplant [ 29 ]. Chronic endometritis, associated with alterations in the uterine endometrial microbiota, is predominantly diagnosed through histopathology. Studies have indicated a significant prevalence of chronic endometritis in RIF patients, along with an altered immune status within the endometrium [ 30 , 31 ].

Thrombophilia, indicated by prothrombin time shortening (PTS), significantly influences the management of recurrent spontaneous abortion (RSA) and plays a crucial role in treatments for RIF [ 32 ]. The hypercoagulable state associated with PTS can present as early as the first trimester of pregnancy, leading to the formation of microthrombi within the uterine spiral arteries or the villous capillaries. This condition can disrupt maternal-fetal circulation, potentially impairing the process of embryo implantation and consequently, increasing the incidence of RIF. It is important to note that this hypercoagulable state can manifest shortly after embryo implantation, underscoring the intricate relationship between thrombophilia and reproductive challenges [ 33 ]. This early occurrence of a hypercoagulable state, even in the initial stages of pregnancy, necessitates tailored management strategies for individuals with PTS, to address the potential for implantation issues and to mitigate the risk of pregnancy failures associated with RIF.

Hereditary PTS, or hereditary thrombophilia, encompasses genetic disorders characterized by defects in anticoagulant factors or fibrinolytic activity genes, elevating blood clot formation risk. This includes deficiencies in anticoagulant proteins (protein C, protein S, antithrombin), factor V Leiden mutation, hereditary Hyperhomocysteinemia (Hhcy), and prothrombin gene mutations. While strongly associated with deep vein thrombosis and late pregnancy loss, the link between hereditary PTS and early RSA is less clear. Emerging evidence suggests that ART-related embryo implantation failure may involve trophoblast or chorionic villus vascular injury and reduced nutritive layer invasiveness [ 34 ].

Acquired thrombophilia, also known as acquired PTS, encompasses a range of conditions that increase the risk of thrombosis. These conditions include antiphospholipid syndrome (APS), acquired Hhcy, and connective tissue diseases that predispose individuals to thrombosis such as systemic lupus erythematosus (SLE). Other factors contributing to acquired thrombophilia include uncontrolled hypertension, long-standing diabetes, chronic kidney disease, prolonged periods of immobilization, and the use of hormone replacement therapy. Notably, ART is a significant risk factor for acquired PTS, increasing venous thromboembolism risk [ 35 ]. While a definitive link between recurrent early implantation failure and acquired thrombophilia has not been established, ART heightens thrombotic event likelihood, adversely affecting embryo implantation. Comprehensive coagulation status assessment in fully informed patients is recommended.

The immunomodulatory mechanisms in embryo implantation are complex and diverse, forming a focal point in both basic and clinical medicine research. Decidual stromal cells in the endometrium are pivotal in regulating trophoblast cell invasion and local maternal immune response suppression, both crucial for successful implantation [ 36 ]. Imbalanced immune responses can lead to implantation failure. Immune factors in pregnancy failure include autoimmune and homologous immune factors.

Autoimmune abnormalities in RIF patients, characterized by the presence of tissue-specific or non-specific autoantibodies, can indicate underlying autoimmune diseases such as APS and SLE [ 37 ]. These autoantibodies may directly contribute to reproductive failures by impairing implantation processes or by inducing an inflammatory environment detrimental to embryo development. These include anti-sperm antibodies (ASA), anti-endometrial antibodies (AEA), anti-ovarian antibodies (AOA), anti-thyroid antibodies (ATA), antiphospholipid antibodies (APL), antinuclear antibodies (ANA), and anti-DNA antibodies. Concurrent autoimmune diseases are common and include APS, SLE, undifferentiated connective tissue disease (UCTD), sjögren’s syndrome (SS), rheumatoid arthritis (RA), and systemic sclerosis (SSc). These conditions can often coexist, indicating a complex interplay of autoimmune mechanisms within an individual, affecting multiple organ systems and leading to a variety of clinical manifestations. Profiling for ANA and APL is crucial in the clinical management of RIF patients with suspected autoimmune etiologies [ 38 ]. ANA profiling helps identify underlying systemic autoimmune conditions, such as SLE, that may affect fertility. Similarly, APL detection is pivotal for diagnosing APS, a condition directly linked to thrombotic events and miscarriage. These profiles not only assist in the initial diagnosis but also guide treatment strategies by identifying specific autoimmune targets and evaluating the efficacy of immunosuppressive therapies. Autoimmune diseases such as SLE, SSc, and RA impair fertility through multiple mechanisms [ 39 ]. For instance, prolonged treatment may lead to advanced maternal age, a known risk factor for reduced fertility. Gonadotoxic drugs used in managing these conditions can cause ovarian failure, while the diseases themselves can lead to reproductive endocrine dysfunction. Furthermore, the hyperactive immune response, characterized by the production of autoantibodies, can interfere with the establishment of maternal-fetal immune tolerance, increasing the risk of infertility and miscarriage. Failure in establishing maternal-fetal immune tolerance contributes to infertility and miscarriage risk, underscoring the complex role of immune system dysregulation in reproductive failures [ 40 ].

APS, characterized by elevated APL, manifests in obstetrics as thrombosis, recurrent pregnancy loss, intrauterine growth restriction, stillbirth, severe preeclampsia, placental insufficiency, and infertility. It is a primary treatable condition linked to autoimmune-related pregnancy loss [ 41 ]. Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are promising markers for APS. Immunoglobulin G (IgG) type aPS/PT antibodies and IgG type anti- β 2 glycoprotein I ( β 2-GP1) domain 1 antibodies exhibit superior diagnostic and prognostic value in APS. Their presence not only aids in accurately diagnosing APS but also in predicting the clinical outcomes and guiding the management of patients with this autoimmune condition. The relationship between atypical antiphospholipid antibodies and recurrent pathological pregnancies is significant, but no randomized controlled trials (RCTs) have explored APS’s role in RIF. Women with autoimmune diseases like SLE, UCTD, RA, and SSc face increased RIF risk [ 42 , 43 , 44 ].

In the context of RIF, the placenta-specific protein encoded by the placenta enriched 1 ( PLAC1 ) gene, predominantly expressed in trophoblast cells, plays a pivotal role in the embryo implantation process. Autoantibodies generated by the immune system against this protein, particularly targeting specific regions, may impede successful embryo implantation. Comparative studies have demonstrated a significant elevation in the levels of these autoantibodies in patients experiencing RIF compared to healthy women of reproductive age who have not undergone implantation failures. This observation underscores the importance of assessing PLAC1-related immune responses in patients with RIF and may guide therapeutic strategies aimed at mitigating immune-mediated barriers to implantation [ 45 ].

Imbalances in maternal-fetal immunity, characterized by abnormalities in the numbers, functions, and interactions of immune cells at the maternal-fetal interface, are associated with RIF [ 46 ]. These immune cells include natural killer (NK) cells, T cells, macrophages, myeloid-derived suppressor cells (MDSCs), decidual stromal cells (DSCs), and trophoblast cells. Disruptions in the equilibrium of these cell types can impede the establishment of a conducive environment for embryo implantation, highlighting the complexity of immune system involvement in successful pregnancy outcomes. Alterations in the expression patterns of specific immune cells or associated mediators, including cytokines and chemokines, may contribute to RIF, yet the precise mechanisms underlying these changes remain an active area of investigation [ 47 ]. NK cells, abundant around uterine trophoblasts during early pregnancy, may regulate physiological trophoblast invasion, immune tolerance, embryonic development, and various immune/metabolic pathways [ 48 ]. Patients with RIF exhibit increased levels of pro-inflammatory cytokines, including interferon-gamma (IFN- γ ), interleukin-1 beta (IL-1 β ), interleukin-6 (IL-6), and interleukin-4 (IL-4), alongside decreased levels of the anti-inflammatory cytokine transforming growth factor-beta 1 (TGF- β 1). This imbalance between pro-inflammatory and anti-inflammatory cytokines may contribute to the pathophysiology of RIF, highlighting the importance of cytokine regulation in maintaining a conducive environment for embryo implantation [ 49 ]. Studies on endometrial cytokines prior to implantation have revealed that there are positive correlations between Interferon gamma-induced protein 10 (IP-10) and tumor necrosis factor-alpha (TNF- α ) with implantation success and clinical outcomes. Conversely, monocyte chemoattractant protein-1 (MCP-1) and IL-1 β demonstrate negative correlations with these parameters. These findings underscore the complex roles that specific cytokines play in the endometrial environment, influencing the likelihood of implantation success and subsequent clinical outcomes [ 50 ].

Maternal age significantly influences embryo quality in IVF procedures [ 51 ]. Studies have demonstrated a correlation between increased maternal age and a higher incidence of non-diploid embryos, which adversely affects embryo quality and increases implantation failure rates [ 52 ]. Specifically, IVF success rates for women aged ≥ 35 are lower than those for women aged < 35 [ 53 ].

Studies show that in IVF treatments, both age and body mass index (BMI) indicators independently reduce success rates. Specifically, women aged over 40 and those with elevated BMI face increased challenges, notably affecting the effectiveness and leading to conditions like RIF [ 54 , 55 ]. An elevated BMI, particularly above 30 kg/m 2 , is associated with lower embryo implantation rates in IVF procedures. This decrease is likely due to obesity-induced changes in endometrial receptivity and follicular function [ 56 , 57 ].

The smoking history of both partners is also a significant factor in RIF [ 58 ]. In female patients with over five years of smoking history, negative impacts include reduced egg retrieval, increased cycle cancellation rates, and altered ovarian response to stimulation [ 59 ]. This effect is primarily due to cigarette toxins interfering with estradiol production during the follicular phase, impacting corpus luteum formation and embryo implantation [ 60 , 61 ]. Furthermore, high serum cotinine levels in female smokers correlate with fewer retrieved eggs and reduced availability of high-quality embryos, consequently increasing the likelihood of negative pregnancy outcomes [ 62 ]. In males, smoking leads to increased reactive oxygen species in seminal plasma, altered sperm microRNA expression, and increased sperm DNA fragmentation, all contributing to diminished sperm quality [ 63 ].

The understanding of RIF has expanded to encompass the significant role of paternal factors alongside maternal contributions. Among these, paternal thrombophilia, particularly the M2/ANXA5 haplotype, has garnered attention for its potential impact on RIF [ 64 ]. This genetic predisposition to increased clot formation, more prevalent in fathers of RIF patients, suggests its influence on key reproductive processes including placental development and embryo-maternal interactions. Such insights into paternal genetic factors urge a comprehensive evaluation in the context of RIF.

While the genetic aspects draw considerable focus, the broader spectrum of male fertility, such as sperm quality, has also been under investigation for its role in RIF [ 65 ]. Emerging research has explored the relationship between suboptimal sperm quality and its effects on embryo development and early placental function. However, the link between specific male fertility issues, like sperm DNA fragmentation, and RIF outcomes remains ambiguous. A notable study involving a small patient cohort indicated no significant correlation between sperm DNA fragmentation index and RIF outcomes [ 66 ]. This finding suggests that, despite the intuitive connection between sperm quality and reproductive success, the direct association of certain male fertility variables with RIF is not definitively supported by the current body of research.

Given this landscape, the routine assessment of sperm DNA fragmentation index as a predictive measure for RIF is currently not recommended [ 67 ]. This stance reflects a cautious approach, acknowledging the complex and multifactorial nature of RIF, where the interplay of numerous paternal and maternal factors contributes to the condition. It underscores the necessity for further research to unravel the intricate dynamics between male fertility issues and RIF, aiming to enhance the understanding and management of this challenging condition.

In conclusion, the exploration of partner-related factors in RIF highlights the importance of considering both paternal genetic predispositions, such as the M2/ANXA5 haplotype, and broader aspects of male fertility in the comprehensive assessment and management of RIF. The nuanced interplay between these factors and their impact on successful implantation and pregnancy emphasizes the need for ongoing research to clarify their roles and inform effective interventions.

In summarizing the various factors contributing to RIF and their corresponding optimized treatment approaches, Table 1 (Ref. [ 7 , 9 , 12 , 13 , 18 , 28 , 40 , 51 , 58 , 61 , 66 , 68 , 69 , 70 ]) and Fig. 1 provide comprehensive overviews. Table 1 serves as a quick reference, detailing the etiology, clinical profile factors, and recommended treatment strategies for each identified cause of RIF. Complementing this, Fig. 1 offers a graphical representation of these elements, visually demonstrating the complex interplay between the etiology and treatment of RIF. Together, these resources emphasize the necessity for individualized treatment plans, catering to the multi-faceted nature of RIF.

Etiology	Clinical profile factors	Optimized treatment	Reference
General health risks	Advanced maternal age ( 35 years)	Oocyte cryopreservation, personalized controlled ovarian stimulation, enhanced embryo selection, and oocyte donation are advanced fertility treatments aimed at preserving eggs, stimulating optimal egg production, selecting the best embryos, and utilizing donor eggs for assisted reproduction, respectively.	Ubaldi FM . (2019) [ ].
	Obesity (BMI 30 kg/m )	Non-pharmacological interventions: weight management and nutritional supplementation—lifestyle changes including diet and exercise to optimize body weight and nutritional status.	Collins GG . (2015) [ ].
	Long-term smoking history ( 5 years)	Lifestyle modification—changes in daily habits to improve overall health.	Collins GG . (2015) [ ].
	Inappropriate endometrial receptivity	Intrauterine hCG, PRP, PBMCs, G-CSF infusions, and ERA—a combination of treatments involving hormones, plasma, cells, and endometrial receptivity analysis to enhance implantation success.	Craciunas L . (2019) [ ].
	Genetic factors in fertility	PGT-A—preimplantation genetic testing for aneuploidies, a technique to assess embryos for chromosomal normalcy before transfer.	Sciorio R . (2020) [ ].
Endocrine system disorders	Corpus luteum insufficiency	Additional progesterone supplementation—use of progesterone to support the uterine lining and encourage implantation.	Duncan WC (2021) [ ].
	Thyroid disorders impacting fertility	Levothyroxine supplementation for hypothyroidism—hormonal supplementation to treat underactive thyroid, which can affect fertility.	Velkeniers B . (2013) [ ].
	Insulin resistance and hyperinsulinemia	Insulin-sensitizing agents: metformin and troglitazone—medications to improve insulin sensitivity.	Sakumoto T . (2010) [ ].
Reproductive microbiome environment	Reproductive tract dysbiosis	Administration of antibiotics or probiotics—use of antibiotics to treat infections and probiotics to balance the microbiome.	Han Y . (2021) [ ].
Reproductive microbiome environment	Chronic endometritis as a fertility factor	Antibiotics therapy—specific antibiotic treatments to address bacterial infections that could hinder implantation.	Cheng X . (2022) [ ].
Anatomical factors in fertility	Anatomical fertility impediments: müllerian duct malformations, uterine fibroids, adenomyosis, endometrial polyps, intrauterine adhesions, hydrosalpinx	Hysteroscopy, surgical intervention—diagnostic and corrective surgery to examine and treat uterine abnormalities.	Chan YY . (2011) [ ].
Prothrombotic conditions	Abnormal thrombophilia screening outcomes	LMWH treatment—low molecular weight heparin therapy to reduce the risk of blood clots, which can affect implantation.	Nelson SM . (2008) [ ].
Immunological factors affecting fertility	Autoimmune diseases affecting fertility: APS, SLE, UCTD, SS, RA, SSc	Aspirin, low-dose unfluorinated glucocorticoids, hydroxychloroquine, sulfamazine, tacrolimus, and cyclosporine, supplemented with low molecular weight heparin—a regimen of medications to manage inflammation and immune response, alongside blood-thinning agents.	Andreoli L . (2017) [ ].
Immunological factors affecting fertility	Maternal-fetal immunological imbalance	IVIG or plasma exchange therapy—intravenous immunoglobulin or plasma exchange procedures to modify immune system activity.	Abdolmohammadi-Vahid S . (2019) [ ].
Male reproductive factors	Poor sperm quality	IMSI—intracytoplasmic morphologically selected sperm injection, a technique to select the best sperm for injection into an egg.	Coughlan C . (2015) [ ].

BMI, body mass index; hCG, human chorionic gonadotropin; PRP, platelet-rich plasma; PBMCs, peripheral blood mononuclear cells; G-CSF, granulocyte colony-stimulating factor; ERA, endometrial receptivity array; PGT-A, preimplantation genetic testing for aneuploidy; LMWH, low molecular weight heparin; APS, antiphospholipid syndrome; SLE, systemic lupus erythematosus; UCTD, undifferentiated connective tissue disease; SS, sjögren’s syndrome; RA, rheumatoid arthritis; SSc, systemic sclerosis; IVIG, intravenous immunoglobulin; IMSI, intracytoplasmic morphologically selected sperm injection.

Graphical overview of recurrent implantation failure (RIF) etiology and treatment approaches. IMSI, intracytoplasmic morphologically selected sperm injection; IVIG, intravenous immunoglobulin; hCG, human chorionic gonadotropin; G-CSF, granulocyte colony-stimulating factor.

Couples are advised to regulate their weight, adhere to a nutritious diet, maintain consistent sleep patterns, participate in suitable physical activities, abstain from smoking, moderate alcohol intake, focus on psychological well-being, and pursue psychological support when warranted [ 58 ]. Multidisciplinary consultation is recommended for patients with comorbidities to effectively manage their health conditions.

The inclusion of progesterone support is critical in IVF protocols. Saccone G et al . [ 71 ] systematic review and meta-analysis highlighted the substantial benefits of progesterone in early pregnancy, particularly for women with recurrent pregnancy loss. Dydrogesterone, especially when combined with ART, outperforms other progesterone types. A comparison of oral desogestrel and vaginal medications revealed that the former is associated with fewer side effects and greater patient compliance [ 72 ]. Thus, the integration of progesterone, especially oral gestrol into IVF protocols, is pivotal in enhancing pregnancy and live birth rates among RIF patients, particularly during the luteal phase of treatment. Nonetheless, additional research is required to confirm these results.

In managing RIF, effective intervention in chronic endometritis (CE) and abnormalities of reproductive anatomy are crucial. Patients diagnosed with CE through hysteroscopy and culture benefit significantly from antibiotic treatment, which has shown efficacy in resolving the majority of infections and thus improving success rates in future IVF cycles [ 68 ]. Patients experiencing pathogen clearance post-antimicrobial treatment exhibit markedly higher clinical pregnancy and live birth rates compared to those with persistent infections [ 73 ]. Recommended empirical antibiotic treatments include doxycycline (100 mg, twice daily, orally for 14 days) and a combination of levofloxacin (400 mg) with metronidazole (500 mg, once daily, orally for 14 days). Ciprofloxacin (500 mg, twice daily, orally for 10 days) is often prescribed for gram-negative bacteria, while amoxicillin-clavulanate (1 g, twice daily, orally for 8 days) targets gram-positive bacteria. In cases of persistent CE, minocycline (100 mg, twice daily, orally for 12 days) is administered. Current advancements, including non-invasive techniques like sequencing and quantitative polymerase chain reaction (PCR) detection of endometrial fluid, are increasingly employed for diagnosing CE, enabling more precise guidance on antibiotic therapy [ 74 ].

Concurrently, addressing submucosal fibroids, uterine polyps, intrauterine adhesions, and hydrosalpinx, frequently associated with RIF, is essential. Hysteroscopy is the preferred method for evaluating these anatomical issues. Patients with submucosal fibroids generally have lower implantation and live birth rates. Treatment considerations for these fibroids, especially during hysteroscopic myomectomy, involve assessing the size of the fibroid and its impact on the uterine cavity [ 75 ]. Removing endometrial polyps has been shown to significantly increase clinical pregnancy rates in intrauterine insemination [ 76 ]. Although the impact of intrauterine adhesion separation on implantation rates is not definitively established, severe adhesions are known to negatively influence pregnancy outcomes [ 77 ]. Postoperative administration of estrogen and progesterone aids in endometrial growth and prevents re-adhesion in patients with severe intrauterine adhesions. For moderate to severe hydrosalpinx, surgical interventions such as tubal resection or occlusion are shown to enhance embryo implantation success in IVF [ 78 ]. Notably, patients with bilateral hydrosalpinx undergoing tubal resection demonstrate significant improvements in clinical pregnancy and live birth rates in subsequent IVF cycles [ 79 , 80 ].

In the management of RIF, optimizing IVF protocols and enhancing endometrial receptivity are integral. Selecting a tailored controlled ovarian hyperstimulation protocol is essential in RIF treatment, involving decisions on the optimal stimulation regimen, evaluating the necessity for pretreatment, determining the appropriate starting dose, timing and method for trigger administration, and devising effective embryo transfer strategies. Additionally, special attention should be given to luteal phase support. It’s noteworthy that high-dose gonadotropin may increase the risk of early embryonic aneuploidy and reduce successful implantation rates [ 81 ]. Assisted hatching (AH), which involves thinning of the zona pellucida using chemical, mechanical, or laser methods, may improve outcomes for patients over 38 years old [ 82 ]. However, a rigorous RCT of 796 RIF patients showed no significant difference in clinical pregnancy rates post-AH [ 83 ].

The selection of ovarian stimulation protocols directly impacts the number and quality of retrieved oocytes and embryos, thus influencing reproductive outcomes. Individualized treatment plans for RIF patients should be based on their medical history and previous ovarian stimulation outcomes. In scenarios where a sufficient number of embryos are available, employing frozen-thawed blastocyst transfer is recommended [ 84 ]. Sequential embryo transfer has been shown to improve endometrial receptivity [ 85 ], though the associated risks of multiple pregnancies should not be overlooked. Given the mixed results regarding the efficacy of AH in RIF, cautious application is advised.

In the realm of RIF, alterations in endometrial receptivity play a crucial role, with innovative therapeutic approaches like intrauterine infusion emerging to address this challenge [ 86 ]. This technique involves administering agents such as human chorionic gonadotropin (hCG), autologous platelet-rich plasma (PRP), peripheral blood mononuclear cells (PBMCs), and granulocyte colony-stimulating factor (G-CSF) directly into the uterus, aiming to enhance its receptivity [ 87 , 88 , 89 , 90 ]. The underlying principle of intrauterine infusion focuses on modifying the endometrial environment to foster conditions favorable for implantation by promoting endometrial regeneration, thickening, and enhancing immunological tolerance at the maternal-fetal interface.

For instance, hCG is thought to stimulate the secretion of growth factors essential for successful implantation, while PRP’s growth factors may regenerate and repair the endometrium. Similarly, PBMCs could modulate the immune environment to support implantation, and G-CSF might improve endometrial thickness and quality. Despite the potential of hCG intrauterine infusion to increase embryo implantation rates in infertility cases, its efficacy in RIF patients is under debate, largely due to the lack of standardized protocols regarding dosage and infusion duration [ 91 , 92 ].

The effectiveness of intrauterine infusions in RIF, therefore, remains a controversial topic, underscoring the need for further research to establish standardized treatment protocols. Such research would elucidate the mechanisms of action of these treatments and refine their clinical application, potentially offering new avenues for overcoming RIF.

In the treatment of RIF, the use of antithrombotic therapy and immunotherapy plays a crucial role, particularly for women with predispositions to certain conditions. Women undergoing ART-assisted reproduction with a tendency for thrombosis may benefit from low molecular weight heparin (LMWH) therapy under fully informed consent, as LMWH has shown to reduce trophoblast apoptosis, promote angiogenesis and trophoblast invasion, thereby improving embryo implantation success rate and live birth rate [ 69 , 93 , 94 ].

Immune dysfunction, categorized into autoimmune and alloimmune factors, significantly contributes to RIF. For women with rheumatic immune diseases, such as systemic lupus erythematosus, adherence to guidelines, including routine low-dose aspirin and specific immunosuppressive agents during pregnancy, is essential. Tacrolimus, in particular, shows promise in managing RIF resulting from immune dysregulation [ 95 ]. In treating RIF-associated antiphospholipid syndrome, an approach similar to obstetric antiphospholipid syndrome is applied, involving low-dose aspirin and LMWH, with hydroxychloroquine recommended for more complex cases. Secondary antiphospholipid syndrome requires addressing the underlying primary disease.

The role of uNK in facilitating normal trophoblast invasion and the formation of the placenta is crucial. Treatments such as intravenous immunoglobulin (IVIG) are known to enhance the function of regulatory T cells (Tregs) and reduce the cytotoxicity of T helper 1 (Th1) cells, proving to be effective in cases of RIF. This approach highlights the significance of modulating immune cell interactions within the uterine environment to support successful implantation and pregnancy outcomes [ 70 , 96 , 97 , 98 , 99 ]. However, treatments such as Intralipid, a 20% fat emulsion, have shown mixed results, with a 2019 study reporting no significant improvement in outcomes following its administration [ 100 ]. The use of PBMCs infusion, based on enhancing embryo implantation through locally implanted immune cells, has demonstrated varied clinical outcomes [ 101 , 102 , 103 ]. G-CSF, important for neutrophil proliferation and differentiation, has been associated with increased implantation rates when used intrauterine [ 104 ]. Despite the potential benefits of these treatments, due to limitations in randomized controlled trial data, small sample sizes, and study heterogeneity, routine clinical implementation of immunotherapy in RIF is not recommended without conducting standardized clinical trials with informed patient consent.

Genetic screening is advised for RIF couples with identified chromosomal anomalies, as chromosomal irregularities in embryos are a significant factor contributing to RIF. While preimplantation genetic testing for aneuploidy (PGT-A) can notably enhance implantation rates in cases where both partners have normal chromosomes [ 105 , 106 ], its use in RIF remains a subject of debate. This debate centers not only on the challenges in identifying mosaic embryos and the risk of false positives but also on the recognition that PGT-A, despite proving embryos to be euploid, cannot guarantee successful implantation [ 107 ]. Furthermore, it is imperative to consider the potential adverse effects associated with the embryo biopsy procedure utilized in PGT-A. Alteri A et al . [ 108 ] underscore the lack of definitive evidence fully addressing the potential obstetric, neonatal, or long-term consequences of embryo biopsy. While the evidence is limited and subject to controversy, there are indications that embryo biopsy at the cleavage stage may be associated with an increased risk of low birth weight and small for gestational age neonates compared to infants born from non-biopsied embryos. An increase in preterm deliveries and birth defects has also been suggested in cases of trophectoderm biopsy. For both cleavage and blastocyst stage biopsies, an elevated risk for hypertensive disorders of pregnancy was observed. However, these associations may be confounded by other embryo manipulation procedures or inherent patient or population characteristics. Given the insufficient evidence to assess the obstetric, neonatal, and long-term health outcomes following embryo biopsy, the development of invasive preimplantation genetic testing (PGT) strategies should proceed with caution. The pursuit of non-invasive methods, based on the analysis of embryo cell-free DNA, is advocated to circumvent the potential limitations and risks associated with embryo biopsy procedures.

In the context of RIF, male factors, especially sperm quality, play a crucial role in the early development of the embryo and the success of implantation. Intracytoplasmic morphologically selected sperm injection (IMSI), a technique that involves the selection of high-quality sperm for injection into the oocyte, has been demonstrated to significantly enhance implantation, clinical pregnancy, and live birth rates in patients experiencing RIF. This method underscores the importance of sperm quality in reproductive success and offers a targeted approach to overcome certain male factor infertility issues contributing to implantation failures [ 109 ]. However, the criteria for sperm selection in IMSI remain under debate, and there is a lack of conclusive evidence supporting its advantages [ 110 ]. As such, this area necessitates further research to establish standardized criteria and validate its efficacy.

Building upon the comprehensive exploration of treatment strategies in previous sections, we present a vital tool for clinical application. Fig. 2 , titled ‘Diagnostic and Treatment Process Flowchart for Recurrent Implantation Failure Patients’, offers a succinct and structured pathway for diagnosing and treating RIF. This flowchart is designed to assist clinicians in navigating the complexity of RIF management, ensuring a streamlined and effective approach to patient care. It delineates a step-by-step process, from initial patient consultation through to specific therapeutic interventions, optimizing the clinical decision-making process.

Diagnostic and treatment process flowchart for recurrent implantation failure patients. PGT-SR, preimplantation genetic testing-structural rearrangements; ASA, anti-sperm antibodies; AEA, anti-endometrial antibodies; AOA, anti-ovarian antibodies; ATA, anti-thyroid antibodies; APL, antiphospholipid antibodies; ANA, antinuclear antibodies; APS, antiphospholipid syndrome; SLE, systemic lupus erythematosus; UCTD, undifferentiated connective tissue disease; SS, sjögren’s syndrome; RA, rheumatoid arthritis; SSc, systemic sclerosis.

In addressing RIF, it is paramount to understand the patient’s comprehensive medical history. Chromosomal abnormalities in embryos are a prevalent cause of implantation failure, necessitating investigations into endometrial factors such as injury, adhesion, inflammation, or abnormal hyperplasia. Additionally, conditions like thromboembolic predispositions and immune-related disorders, including antiphospholipid syndrome, require targeted interventions. The emerging focus on endometrial receptivity testing and reproductive tract microbiome analysis offers personalized treatment insights, though these methods still demand further validation.

Considering the complexity of RIF’s etiology, a multi-pronged treatment approach is essential. Clinicians must continuously refine their strategies based on the latest research to enhance treatment efficacy, aiming to increase the chances of successful pregnancies for RIF patients. The intricate nature of RIF’s causes underscores the need for future treatments to incorporate multi-faceted diagnostic approaches, tailoring individualized plans for patients. While advancements in diagnostic technologies show promise, further studies are necessary to validate their effectiveness and precision in understanding the mechanisms behind potential pathogenic factors.

RIF remains a multi-etiological and heterogeneous disorder. The challenge in achieving a unified understanding of its etiology lies partly in the difficulties of pinpointing specific causes in patients and partly in the lack of high-quality, evidence-based diagnostic methods. As research progresses, our comprehension and management of RIF are expected to evolve, becoming more precise and effective. This advancement is critical for the field of reproductive medicine and offers hope to those grappling with this complex condition.

AEA, anti-endometrial antibodies; AH, assisted hatching; AOA, anti-ovarian antibodies; aPS/PT, antiphospholipid/prothrombin complex antibodies; APS, antiphospholipid syndrome; APL, anti-phospholipid antibodies; ART, assisted reproductive technologies; ASA, anti-sperm antibodies; ATA, anti-thyroid antibodies; BMI, body mass index; CE, chronic endometritis; ERA, endometrial receptivity array; G-CSF, granulocyte colony-stimulating factor; hCG, human chorionic gonadotropin; Hhcy, hyperhomocysteinemia; IMSI, intracytoplasmic morphologically-selected sperm injection; IVF, in vitro fertilization; IVIG, intravenous immunoglobulin; LMWH, low molecular weight heparin; PCOS, polycystic ovary syndrome; PBMCs, peripheral blood mononuclear cells; PGT-A, preimplantation genetic testing for aneuploidy; PRP, platelet-rich plasma; PTS, prethrombotic status; RA, rheumatoid arthritis; RCT, randomized controlled trial; RIF, recurrent implantation failure; RSA, recurrent spontaneous abortion; SS, sjögren’s syndrome; SLE, systemic lupus erythematosus; SSc, systemic sclerosis; uNK, uterine natural killer cells; UCTD, undifferentiated connective tissue disease.

ZH and RM were the primary analysts for this review. They conducted comprehensive literature searches and synthesized the findings, and were responsible for drafting the initial manuscript. NL, LL and YL, as the lead clinicians for recurrent implantation failure, provided valuable insights that significantly shaped the core content of this review. YK and XM contributed extensively to the organization and compilation of research for this study. ZW and XL contributed to the conceptualization and oversight of the review. XL also significantly revised and approved the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Not applicable.

We extend my sincere gratitude to the team at the Department of Reproductive Medicine, the First People’s Hospital of Yunnan Province, for their invaluable clinical insights into recurrent implantation failure. Their contributions, encompassing a wealth of practical experiences and expertise, have been instrumental in shaping the perspectives and methodologies employed in this review. Their guidance in interpreting clinical data and refining research approaches significantly enhanced the rigor and depth of this study.

This review was supported by grants from the National Natural Science Foundation of China (82260292, 82360305); the Open Project of Yunnan Provincial Reproductive and Obstetrics and Gynecology Clinical Medicine Center (2022LCZXKF-SZ16); the Open Project of Yunnan Provincial Key Specialty of Gynecology (2022FKZDZK-13); the Social development projects of Yunnan Province (202302AA310044); the Reproductive Obstetrics and Gynecology Clinical Center of Yunnan Province (2022LCZXKF-SZ05); the Yunnan Revitalization Talent Support Program (XDYC-MY-2022-0055); and the Kunming University of Science and Technology Medical School research development fund project (SRDP-2023-003). The funders had no role in study design; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to submit the article for publication.

The authors declare no conflict of interest.

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Journal of Intensive Care volume 12 , Article number: 32 ( 2024 ) Cite this article

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Post-cardiac arrest syndrome (PCAS) presents a multifaceted challenge in clinical practice, characterized by severe neurological injury and high mortality rates despite advancements in management strategies. One of the important critical aspects of PCAS is post-arrest lung injury (PALI), which significantly contributes to poor outcomes. PALI arises from a complex interplay of pathophysiological mechanisms, including trauma from chest compressions, pulmonary ischemia–reperfusion (IR) injury, aspiration, and systemic inflammation. Despite its clinical significance, the pathophysiology of PALI remains incompletely understood, necessitating further investigation to optimize therapeutic approaches.

This review comprehensively examines the existing literature to elucidate the epidemiology, pathophysiology, and therapeutic strategies for PALI. A comprehensive literature search was conducted to identify preclinical and clinical studies investigating PALI. Data from these studies were synthesized to provide a comprehensive overview of PALI and its management.

Epidemiological studies have highlighted the substantial prevalence of PALI in post-cardiac arrest patients, with up to 50% of survivors experiencing acute lung injury. Diagnostic imaging modalities, including chest X-rays, computed tomography, and lung ultrasound, play a crucial role in identifying PALI and assessing its severity. Pathophysiologically, PALI encompasses a spectrum of factors, including chest compression-related trauma, pulmonary IR injury, aspiration, and systemic inflammation, which collectively contribute to lung dysfunction and poor outcomes. Therapeutically, lung-protective ventilation strategies, such as low tidal volume ventilation and optimization of positive end-expiratory pressure, have emerged as cornerstone approaches in the management of PALI. Additionally, therapeutic hypothermia and emerging therapies targeting mitochondrial dysfunction hold promise in mitigating PALI-related morbidity and mortality.

PALI represents a significant clinical challenge in post-cardiac arrest care, necessitating prompt diagnosis and targeted interventions to improve outcomes. Mitochondrial-related therapies are among the novel therapeutic strategies for PALI. Further clinical research is warranted to optimize PALI management and enhance post-cardiac arrest care paradigms.

Graphical Abstract

Introduction

Despite advancements in the management of post-cardiac arrest syndrome (PCAS), a significant proportion of patients with PCAS experiences severe neurological injury and high mortality rates [ 1 , 2 , 3 , 4 ]. PCAS is characterized by a complex interplay of systemic inflammation, ischemia–reperfusion (IR) injury, and multi-organ dysfunction, all of which contribute to the overall poor prognosis [ 5 , 6 , 7 , 8 ]. Emerging evidence has identified the lungs as a crucial organ after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), with lung injuries including acute respiratory distress syndrome (ARDS), significantly impacting patient outcomes [ 9 , 10 , 11 , 12 , 13 , 14 ].

The pathogenesis of post-arrest lung injury (PALI) is complex, involving trauma from chest compressions, pulmonary IR injury, aspiration, hyperoxia, and systemic inflammation [ 9 , 11 , 12 , 15 ]. The specific underlying mechanisms remain still largely elusive, necessitating further research. This review aims to elucidate the complex pathophysiological landscape of PALI and emphasize the importance of lung-protective strategies in improving patient outcomes post-CA.

Epidemiology

The incidence and clinical significance of PALI have gained substantial attention in recent years. Emerging evidence have suggested the prevalence of pulmonary complications in the aftermath of CA, particularly following the successful return of spontaneous circulation (ROSC), with up to 50% of CA survivors developing acute lung injury (ALI) [ 11 , 16 , 17 , 18 , 19 ] (Table 1 ). Clinical studies have identified lung injury rates as high as 79% in patients undergoing CPR, as detected by computed tomography (CT) [ 16 , 17 ]. The ALI following CPR can manifest as lung edema, thoracic skeletal injuries, and lung IR injury [ 17 , 18 ]. These findings underscore the substantial burden of lung injury in PCAS, necessitating comprehensive evaluation and management of pulmonary complications.

Pathophysiology

Primary causes of pali.

The multifactorial etiologies, which contribute to the complex pathophysiology of PALI, include trauma induced by chest compressions, barotrauma resulting from mechanical ventilation, aspiration during and after CA/CPR, and IR injury within the pulmonary system post-CA [ 15 ].

Traumatic lung injury, which manifests as pulmonary contusion induced by chest compression and barotrauma, is frequently observed with pathologic features such as pulmonary hemorrhage, pulmonary edema, and atelectasis secondary to physical disruption of alveolar capillary membranes [ 14 , 20 ]. The incidence of chest compression-related pulmonary contusions ranges from 41 to 100%, with bilateral lung contusions seen in most of CA patients [ 16 , 17 , 18 , 19 ].

Aspiration is frequently observed during CA/CPR, with a high incidence of 20–65% [ 21 , 22 , 23 , 24 ]. In particular, in patients with OHCA, aspiration of gastric contents has been reported to occur in approximately 30% of patients during or after CPR [ 25 , 26 ]. Aspiration of acidic gastric fluid or oropharyngeal secretions can result in increased alveolar-capillary permeability, further increasing inflammation and exacerbating lung injury [ 24 ]. Complications of aspiration in patients with CA can lead to respiratory failure. One study reported that aspiration was associated with a significantly lower 30-day survival rate compared to CA due to other causes of respiratory failure [ 27 ]. Although it is often difficult to determine whether aspiration occurred before, during, or after CPR, a higher level of care needs to be considered to prevent aspiration and the subsequent severity of PALI.

Pulmonary IR injury is a complex pathophysiological process that significantly contributes to morbidity and mortality in a wide range of clinical scenarios, including PCAS, lung transplantation, cardiopulmonary bypass, and ARDS. This condition is marked by a pronounced increase in alveolar-capillary permeability, a hallmark of the disrupted pulmonary barrier function [ 28 ]. At the cellular level, IR injury in the lung is characterized by the induction of apoptosis and the robust production of reactive oxygen species (ROS), initiating a cascade of inflammatory responses. Central to this inflammatory milieu is the upregulation of a spectrum of cytokines, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and a series of interleukins such as interleukin (IL)-8, IL-10, IL-12, and IL-18 [ 29 , 30 ]. These mediators play pivotal roles in orchestrating the local and systemic inflammatory response, exacerbating tissue damage during the critical phases of circulatory disruption and subsequent reperfusion. Cell apoptosis in the lung after IR could be more detrimental to the lung than cell necrosis and associated inflammation [ 31 ]. Moreover, recent studies have shown that mitochondrial DNA (mtDNA) has been associated with the development of ARDS [ 32 , 33 , 34 , 35 , 36 ]. Elevated circulating levels of mtDNA are found in patients with ALI, which correlates with poor outcomes [ 36 , 37 ], suggesting plasma mtDNA released from damaged mitochondria as damage-associated molecular patterns (DAMPs) may induce lung injury.

ARDS post-CA

ARDS frequently follows both out-of-hospital cardiac arrest (OHCA) [ 38 ] and in-hospital cardiac arrest (IHCA) [ 39 ], with PALI presenting as a spectrum of pulmonary damage. The multifaceted nature of PALI, compounded by systemic IR injury and inflammatory response, can exacerbate poor outcomes, with high oxygen concentrations during CPR, pulmonary contusions, and aspiration further increasing the risk of ARDS through oxidative stress mechanisms [ 40 , 41 , 42 ]. A retrospective analysis of OHCA patients by Johnson et al . reported a 48% incidence of ARDS among mechanically ventilated OHCA patients, with an average P / F ratio of 155 mmHg, corresponding to moderate ARDS. Shih et al. reported that approximately three-quarters of IHCA patients experienced ARDS post-ROSC [ 39 ]. In an unadjusted analysis, the presence of ARDS was linked to fewer alive-and-ventilator-free days across 28 days with a median of 1 day as compared to 18 days in patients without ARDS, though this association did not achieve statistical significance upon multivariate analysis [ 39 ]. These findings indicate that ARDS is a frequent complication post-CA, suggesting an important area for future therapeutic strategies to improve outcomes post-CA. Given its prevalence and impact, ARDS management in PCAS patients should align with established ARDS protocols to mitigate the risks of prolonged ventilation and increased mortality.

Lung compliance post-CA

Previous research has demonstrated that pulmonary dysfunction following CA is associated with impaired gas exchange, increased pulmonary edema, and the release of pro-inflammatory cytokines [ 43 ]. These factors can further contribute to reduced lung compliance and exacerbate lung injury. Additionally, the utilization of mechanical ventilation, almost always required for the management of PCAS, can impact lung compliance, and potentially contribute to lung injury if not diligently controlled [ 44 ].

Respiratory system compliance, consisting of pulmonary and chest wall compliance, refers to the lung capacity to expand and adapt to volume changes during the respiratory cycle. Pulmonary components are influenced by various factors, including lung tissue elasticity and the presence of pathologic conditions. The chest wall compliance is often affected by intrinsic respiratory muscle tone, and certain pathological conditions such as deformities of the chest wall from traumatic rib fractures or burns. Following CPR, decreased lung compliance may be a result of factors such as IR injury, systemic inflammation, and ventilation-associated lung injury (VALI). Chest wall compliance may be affected by chest wall trauma from CPR [ 45 , 46 ]. A study assessing lung compliance in patients with PCAS reported a mean lung compliance of 0.051 ± 0.011 L/cm H 2 O [ 46 ], with a notable decrease at lower lung volumes suggesting the risk of alveolar collapse. The duration of CPR further exacerbates this decline in compliance. Furthermore, decreased lung compliance, a prominent feature of ARDS, may explain higher risk of lung injury following CA. This was demonstrated in a study of PCAS patients who developed ARDS [ 47 ]. This relationship underscores the need for vigilant respiratory management aimed at preserving lung function and improving survival outcomes with intact neurological function.

Pulmonary edema and mechanical chest compression

Pulmonary edema following resuscitation is typically transient and considered hydrostatic in nature. However, the exact mechanisms underlying this condition remain to be definitively determined. Potential contributing factors include decreased left ventricular contractility, ineffective chest compressions that fail to adequately propel blood forward, and the reverse flow of blood into the lungs. This backward movement of the blood can cause elevated left ventricular filling pressures and left atrial pressures, further contributing to pulmonary edema during and immediately after CA, while the heart is still stunned.

Mechanical chest compression (MCC) during CPR is associated with an increased incidence of pulmonary edema compared to manual compressions [ 11 ]. The pulmonary edema which is characterized by increased lung fluid volume and weight, along with reduced oxygenation and respiratory system compliance, underscores the physiological impact of MCC resuscitation on lung condition [ 11 ]. Magliocca et al . demonstrated that MCC notably exacerbates CPR-induced lung edema, a finding consistent across animal models and OHCA patients [ 11 ]. However, no worsening has been observed in survival to discharge or length of ICU stay due to the MCC effect. The hemodynamic effects of piston-based devices, while improving blood flow, may also exacerbate vascular congestion by the pressure aspiration effect, hinting at a complex interplay of factors leading to transient pulmonary edema [ 48 ].

Assessment and diagnosis

Diagnostic imaging plays a crucial role in evaluating the causes and complications after CA/CPR. Imaging techniques, such as chest x-rays, CT, and lung ultrasound, are instrumental in identifying common lung injury manifestations, such as ground-glass opacities predominantly located in the posterior segments of the lungs [ 16 ]. Lung injuries resulting from chest compressions during CPR can lead to pulmonary hemorrhage and edema. These conditions stem from the disruption of alveolar-capillary membranes, pulmonary IR injury, and the aspiration of gastric and oropharyngeal secretions as described above. The differentiation between aspiration pneumonia and lung injury through imaging can be challenging due to overlapping patterns in dependent lung areas [ 16 ].

Chest x-rays can be used to identify chest complications after CA/CPR, including rib and sternal fractures, pericardial effusions, and lung injury [ 49 ]. A study involving chest x-rays of 44 patients post-CA/CPR revealed increased opacities in 63.6% of the cases, underscoring the prevalence of lung injuries [ 16 ]. However, CT scans within the same study group showed a higher detection rate of lung injuries at 79.5%, including in patients with normal chest x-rays, highlighting CT’s superior diagnostic capability [ 16 ].

Quantitative CT evaluation offers a detailed assessment of lung injury severity after successful CPR [ 14 ]. A study using a porcine ventricular fibrillation model revealed ALI on CT, such as intense parenchymal and ground-glass opacifications, which are indicative of pulmonary edema and alveolar damage, respectively [ 14 ]. Further, these changes were more sensitive than the oxygenation index using blood gas analysis, indicating CT’s enhanced sensitivity over traditional blood gas analysis. The utility of CT in detecting pulmonary edema post-resuscitation has been validated in both animal studies and human cases, emphasizing the need for early CT examination for comprehensive lung injury assessment post-CA/CPR [ 11 ]. Clinically, CT must be considered standard of care when feasible in PCAS.

Lung ultrasound emerges as a rapid and non-invasive tool for bedside lung injury assessment and monitoring lung injury post-CA [ 50 , 51 ]. We et al. reported that the lung ultrasound score (LUS), calculated from four findings; (1) presence of lung sliding with A lines or fewer than two isolated B lines, (2) well-defined B lines, (3) multiple coalescent B lines, (4) presence of tissue pattern characterized by dynamic air bronchograms, was useful in assessing lung status and degree of lung injury in a porcine CA model [ 10 ].

The extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI) by the pulse index continuous cardiac output (PiCCO) technology using transpulmonary thermodilution are useful markers of severity of lung injury [ 52 ]. In ARDS patients, a strong correlation exists between LUS, EVLW, and PVPI, with early measurements serving as good prognostic indicators [ 53 , 54 ]. Given the significant correlation of these markers in both ARDS and post-CA contexts, PiCCO technology could aid in detecting lung injuries in PCAS patients, albeit with considerations for its cost, invasiveness, and complexity [ 10 ].

Potential therapeutic strategies for PALI

Tidal volume management.

Following CA/CPR, up to 50% of resuscitated patients develop lung injury that meets the criteria for ARDS during their intensive care unit (ICU) stay, highlighting the need for lung-protective ventilation strategies in patients with PCAS [ 38 ]. A meta-analysis of critically ill non-CA patients without ARDS reported that low tidal volume ( V T ) was associated with lower lung infection, atelectasis, and mortality [ 55 ]. Despite limited data on ventilator management for PCAS, current practices often involve higher V T and driving pressures (Δ P ), which may exacerbate ventilator-induced lung injury (VILI) [ 56 ]. In a study using a two-center retrospective cohort of OHCA patients, Beitler et al. showed that lower V T [< 8 ml/kg predicted body weight (PBW)] was associated with improved functional outcomes [ 57 ]. Furthermore, a preplanned sub-analysis of the Target Temperature Management (TTM)-2 trial by Robba et al. has demonstrated that mechanical output, Δ P , and ventilation rate, as well as positive end-expiratory pressure (PEEP), respiratory plateau pressure ( P PLAT ), and single V T , were independently associated with 6-month mortality in the post-resuscitation respiratory setting [ 58 ]. European guidelines advocate for V T of 6–8 ml/kg PBW in brain-injured and post-CA patients, although evidence in the post-CA context is sparse [ 59 ]. These findings underscore the critical need for lung-protective strategies with lower V T (6–8 ml/kg PBW) to prevent VILI, advocating for more careful and frequent adjustments of ventilator settings in the PCAS care to avoid V T higher than 8 ml/kg PBW. To meet the ventilatory needs of the patient, respiratory rate should be adjusted to allow for a higher minute ventilation to avoid hypercarbic respiratory failure and potential worsening brain injury [ 60 ]. However, it must be emphasized that given frequently hypermetabolic state of PCAS, very high respiratory rates may lead to inappropriately high airway pressures which the clinician should be vigilantly monitoring. Lastly, it must be noted that unless the patient is deeply sedated or paralyzed, the respiratory rate may be centrally driven to be high, irrespective of the respiratory rate set by the ventilator.

Managing hypercapnia

Along with the proper management of V T , the impacts of hypercapnia on cerebral blood flow and intracranial pressure (ICP) are critical considerations in post-CA care. Studies reported that mild hypercapnia improved cerebral oxygenation but did not increase ICP or cerebral edema, suggesting potential therapeutic benefits in the acute phase following resuscitation [ 61 , 62 ]. However, a recent randomized controlled trial (RCT) challenged this notion by demonstrating that, in comatose patients resuscitated after OHCA, targeted mild hypercapnia did not result in superior neurological outcomes at 6 months compared to targeted normocapnia [ 63 ]. Despite this, the absence of consistent evidence regarding the optimal role of hypercapnia post-CA has not deterred the clinical practice of permitting mild hypercapnia as an integral component of lung-protective ventilation strategies. This approach is primarily aimed at reducing the risk of VILI while potentially aiding cerebral perfusion. As such, PaCO 2 levels are often maintained within a target range of 35 to 50 mmHg, striking a balance between ensuring sufficient oxygenation and mitigating the risk of negative cerebral consequences [ 64 ]. This nuanced approach underscores the complexity of managing ventilation in post-CA patients and highlights the need for ongoing research to refine these strategies for optimal patient outcomes.

Optimizing PEEP, plateau pressure, and driving pressure

PEEP is a crucial aspect of mechanical ventilation strategy, especially in the management of PCAS, yet research specifically addressing its optimal use in this patient population remains limited. The application of PEEP for patients with PCAS requires careful consideration, given its potential to influence both pulmonary and cerebral hemodynamics significantly. On one hand, high levels of PEEP can pose risks, such as diminished tissue oxygen delivery resulting from diminished venous return, circulatory impairment and elevated ICP. On the other hand, setting PEEP too low or employing zero PEEP might increase the likelihood of atelectasis and subsequent lung injury, complicating the patient’s recovery process [ 65 , 66 ]. Sutherasan et al. have shown that higher V T , higher P PLAT , and lower PEEP in the first 24 h after ICU admission were associated with an increased risk of developing ARDS or pneumonia in patients initially without lung injury [ 44 ]. This emphasizes the need for careful ventilatory settings to prevent secondary lung complications. Thus, setting PEEP at ≥ 5 cmH 2 O is advisable to prevent atelectasis and protect against PALI, while also considering risks such as dynamic lung hyperinflation, circulatory depression, and brain damage [ 64 , 67 ].

Plateau pressure ( P PLAT ) is a crucial measure in mechanical ventilation, representing the pressure in the airways at the end of inspiration without airflow, thus reflecting mean alveolar pressure without being influenced by airway resistance. Keeping P PLAT < 20 cmH 2 O is recommended to minimize mortality risk, especially in patients without ARDS. This is supported by a study in PCAS cohorts, where maintaining P PLAT < 20 cmH 2 O has been linked to better outcomes and reduced risk of barotrauma, a common complication after resuscitation [ 58 ]. P PLAT < 20 cmH 2 O may be difficult in post-cardiac arrest patients requiring higher PEEP levels.

Driving pressure (Δ P ) is reflecting the stress exerted during the lung expansion, calculated as the difference between P PLAT and PEEP. A sub-analysis of the TTM1 trial reported a median Δ P of 14.7 cmH 2 O in patients with PCAS, with findings indicating that Δ P was an independent factor of higher mortality and adverse neurological outcomes [ 58 ]. However, Δ P does not consider respiratory rate, which itself can contribute to VALI, which is part of PALI [ 68 ]. Lowering Δ P might lead to increase PaCO 2 due to reduced V T , necessitating a higher respiratory rate to maintain constant PaCO 2 levels. For this reason, an equation incorporating both Δ P and respiratory rate (4 × Δ P + respiratory rate) was explored in patients with ARDS and found to strongly correlate with mortality [ 69 ]. This metric was also applied by Robba et al. in a cohort of post-CA patients, revealing a robust association with poor neurological outcomes and increased mortality [ 58 ]. Currently, it is suggested to keep the Δ P < 13 cmH 2 O by adjusting the V T and PEEP level according to the patient’s clinical picture, aiming to optimize lung-protective ventilation strategies [ 64 ].

Extra corporeal membrane oxygenation

The extra corporeal membrane oxygenation (ECMO) has been used an extension of CPR (extracorporeal CPR: ECPR) in recent years [ 70 , 71 , 72 ]. In addition to potentially improved survival rates with favorable neurological outcomes, ECMO is a valuable modality to minimize the risk of PALI, pulmonary congestion, and frequently exacerbated ventilatory support, which may interfere with lung protective ventilation discussed above. However, it must be noted that ECMO may exacerbate pulmonary congestion through aortic retrograde flow resulting in increased left ventricular afterload [ 73 ]. This can be mitigated by running ECMO at the lowest possible flow wares, implementing a percutaneous micro axial pump, or veno-arterial-venous ECMO configuration [ 74 ]. Despite the EOLIA trial’s controversial results, in the case of the development of ARDS, ECMO could be deployed in either veno-venous or veno-arterial configuration to allow for ventilation and oxygenation while the lungs are being rested [ 75 ].

Therapeutic hypothermia

Therapeutic hypothermia, inclusive of TTM, is the primary neuroprotective approach post-CA [ 76 , 77 , 78 ]. The efficacy of therapeutic hypothermia for lung injury, including ARDS, has been reported in both animal and human studies. In injury model such as pulmonary IR injury, pulmonary hypertension, VILI, smoking-induced injury, endotoxemia model, and hemorrhagic shock, therapeutic hypothermia has been reported to suppress lung injury by modulating inducible nitric oxide synthase (iNOS) production, endothelial nitric oxide synthase (eNOS) production, neutrophil activation, or adhesion molecule expression [ 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. An animal study using a rabbit model of ALI has shown that mild therapeutic hypothermia with external cooling reduced lung inflammation and damage and improved oxygenation, likely by lowering levels of inflammatory cytokines, such as TNF-α, IL-6, and IL-8 [ 87 ]. In addition, in an experiment using pig models of oleic acid-induced ARDS, authors reported that the intervention of hypothermia at 32 °C reduced the pathological lung damage and improved lung mechanics [ 88 ]. A retrospective study of 58 patients with ARDS who received muscle relaxation and a pilot feasibility study of 8 patients with severe ARDS with P / F ratio < 150 showed that hypothermia (34–36 °C for 48 h) reduced in-hospital mortality (75% vs 53.4%, p = 0.26) and increased ventilator-free days, while not statistically significant [ 89 ]. Conversely, therapeutic hypothermia is associated with an increased risk of pneumonia, which could worsen PALI [ 90 ].

Wu et al. investigated the impact of therapeutic hypothermia on PALI using a swine model of CA [ 10 ]. In their study, hypothermic animals were cooled to 33 °C for 24 h post-resuscitation, then gradually rewarmed at 1 °C/h for 5 h, while normothermic animals were kept at 37–38 °C. Despite both groups exhibiting PALI, the hypothermia group showed significant improvements in ELWI, PVPI, and P / F ratio, indicating reduced lung injury. Although derived from limited animal research, these findings suggest therapeutic hypothermia could potentially be a viable treatment for PALI.

The Hypothermia After Cardiac Arrest (HACA) study [ 77 ] and a study by Bernard et al. [ 76 ] reported improved neurological prognosis and reduced mortality in patients with ventricular tachycardia or ventricular fibrillation who underwent therapeutic hypothermia, cooled to 32–34 °C, compared to those who were not cooled. These seminal studies have significantly influenced clinical practices in the management of post-CA patients. However, the TTM trial [ 78 ] found that hypothermia at 33 °C did not improve mortality or neurological outcomes in patients following OHCA when compared with normothermia at 37 °C. Subsequently, the HYPERION Trial reported a significant improvement in survival and neurological outcomes at 34 °C for patients with pulseless electrical activity or asystole [ 91 ]. Yet, the TTM2 Trial indicated no difference in neurological outcomes or mortality between temperatures of 33 °C for 24 h and 36 °C for 24 h [ 92 ], suggesting that the effectiveness of hypothermia in PCAS patients remains controversial. Notably, none of these RCTs provides clear evidence regarding the impact of hypothermia on lung function.

Factors associated with mitochondrial pathophysiology

Mitochondria plays an integral role in the development and onset of ALI. DAMPs are a collective term for numerous endogenous risk molecules present in the nucleus, mitochondria, or cytoplasm [ 93 , 94 ], and mtDNA, as mitochondrial DAMPs, has been implicated in sepsis-induced increases lung endothelial cell permeability in ALI [ 95 ]. The presence of large amounts of ROS can upset the balance between mitochondrial dysfunction and mitosis, accelerating sepsis progression and indirectly causing ALI [ 96 ]. Thus, factors related to impaired mitochondrial pathophysiology may be potential therapeutic targets for PALI in patients with PCAS [ 97 ]. Mitochondria-targeted antioxidants can protect against ventilator-induced mitochondrial dysfunction and oxidative stress, suggesting improved outcomes for ALI treated by ventilators [ 98 ]. Furthermore, mitochondrial transplantation, as an emerging technology to replace damaged mitochondria with exogenous healthy mitochondria [ 99 , 100 , 101 ], can significantly improve lung status and reduce lung tissue damage caused by ALI [ 102 ]. Pang et al. showed that in an endotoxin-induced ALI rat model, allogeneic mitochondria administered via the jugular vein accumulated in the lungs, protecting the endothelium of alveolar capillary arrays, and improving gas exchange in the acute phase [ 103 ]. Moreover, Hayashida et al. showed that intravenous administration of allogeneic mitochondria immediately after ROSC improves the lung wet/dry ratio after resuscitation in a rat model of asphyxial CA [ 104 ]. However, since there is currently no clinically available bedside surrogate marker for mitochondrial dysfunction, further translational research is warranted to develop real-time measurement techniques for assessing mitochondrial damage.

Other therapeutic approaches

A Rho kinase (ROCK) is a type of protein kinase that plays a crucial role in cellular processes such as cell contraction, adhesion, motility, and transcriptional regulation. It is activated by the small GTPase RhoA and regulates the phosphorylation of myosin light chain, which affects the remodeling of the cell cytoskeleton. The Rho/ROCK signaling pathway also influences the expression of vascular endothelial-cadherin, which maintains endothelial junction stability, and intercellular adhesive molecule-1, which regulates leukocyte adhesion and transmigration. ROCK inhibition has been found to be effective in reducing damage caused by IR injury and preventing neutrophil recruitment and edema formation in ALI. Fasudil, a Rho kinase inhibitor, is currently used clinically to treat cerebral vasospasms and has shown promising safety profiles in various clinical trials for conditions such as angina, systemic and pulmonary hypertension, stroke, and heart failure. One study demonstrated that pretreatment with fasudil, a medication, can reduce lung injury caused by CA in rats [ 105 ]. Fasudil showed protective effects by decreasing lung edema, oxidative stress, and inflammation. These effects are believed to be mediated through the inhibition of the Rho/ROCK signaling pathway, which is known to be involved in lung IR injury.

Alda-1 is a compound that activates aldehyde dehydrogenase 2 (ALDH2), an enzyme involved in the removal of toxic aldehydic products. The specific agonist of ALDH2, Alda-1, has been shown to protect the lung against different stimuli in various experimental settings, such as acrolein-, hypoxia-, sepsis-, heatstroke-, severe hemorrhagic shock-induced lung injury, regional lung IR injury, and global IR injury [ 106 , 107 , 108 , 109 , 110 , 111 ]. One study aimed to investigate whether Alda-1 treatment could alleviate lung injury after CA/CPR in a swine model [ 112 ]. They found that Alda-1 improved lung function and reduced cell death through the inhibition of apoptosis and ferroptosis, suggesting its potential as a therapeutic approach for lung protection and enhance cell survival in PALI.

Future directions

An overview of PALI outline in our knowledge to date is summarized in Fig. 1 . PALI is thought to be caused by a complex combination of factors associated with CA. The impact of each factor probably varies from the patient’s background, including underlying disease and duration of CA. On the other hand, the incidence and pathogenesis of PALI are gradually becoming clearer with the widespread use of rapid post-arrest CT scans and lung ultrasound. Although the severity of PALI varies, it has been reported that the presence of PALI affects the prognosis of patients after CA, and thus the treatment of PALI and prevention methods are expected to be studied [ 38 , 47 , 113 , 114 , 115 ].

A clinical outline of post-arrest lung injury

ARDS presents primarily as hypoxic respiratory failure, especially in the early acute phase. Systemic and brain tissue hypoxia are associated with worse outcomes in PCAS, and it has been reported that patients who develop ARDS after OHCA are less likely to recover neurologically and be discharged [ 38 ]. The association between ventilation at low tidal volume and improved outcomes after OHCA has been demonstrated, and palliation or risk reduction of ARDS may be an important treatment strategy for improving outcomes, including neurologically intact survival after CA [ 57 ]. Currently, the treatment of PALI is similar to that of ALI and ARDS, with appropriate ventilator settings in post-ROSC respiratory management being critical. In addition, therapeutic hypothermia has been reported to reduce lung injury in animal models as well as in clinical cases. Particularly, in PCAS patients with severe PALI, the reduction of lung injury by TTM may be more important than these side effects, so it is necessary to investigate the settings of TTM and patient criteria for selecting TTM for the treatment of PALI.

In PCAS, mitochondrial dysfunction manifests distinctly across different organs, influenced by their specific metabolic demands and stress responses [ 116 ]. In the lungs, increased oxidative stress and impaired mitochondrial respiration lead to the release of mtDNA, which acts as a DAMP, eliciting inflammatory responses that contribute to ALI. In the brain, mitochondrial dysfunction primarily involves extensive oxidative damage and impaired ATP production, leading to neuronal cell death and neurodegeneration. Cardiac mitochondria experience disrupted electron transport chain function, reduced ATP synthesis, and increased ROS production, resulting in oxidative damage and enhanced apoptosis. Renal mitochondrial alterations include impaired biogenesis and function, elevated oxidative stress, and altered dynamics affecting cellular homeostasis and survival.

The interaction of organs in PCAS is critical due to the interdependence of their functions and the systemic nature of the response to IR injury. Mitochondrial dysfunction in one organ can exacerbate dysfunction in others, creating a vicious cycle of damage. For example, acute lung injury (ALI) increases systemic inflammation and oxidative stress, worsening outcomes in the brain, heart, and kidneys. Understanding these interactions is essential for developing comprehensive treatment strategies that address multi-organ dysfunction in PCAS.

Improvement of mitochondrial function in patients with lung injury is thought to have the potential to improve prognosis as well as lung injury. In particular, mitochondrial transplantation could be a promising therapy to improve lung injury post-CA. However, while the use of animal models has shown that mitochondrial transplantation can accumulate in the injured lungs and reduce lung damage, there are a number of issues that need to be addressed before it can be applied clinically. These include the source of the mitochondria to be transplanted, the timing of the transplant, the indication, the dosage, and the frequency of mitochondrial transplantation. It is essential to develop translational studies to apply mitochondrial transplantation to clinical practice in particular, and it will be necessary to set conditions for clinical application based on these data.

Conclusions

PALI is a pathological condition that has a high overall incidence as a complication and affects the prognosis of patients after CA/CPR. Rapid detection of PALI is essential to ensure prompt etiologic therapy, and the use of diagnostic tools is mandatory. Early quantitative CT evaluation is important to improve the accuracy of clinical diagnosis, and the usefulness of LUS has been reported as a bedside assessment of lung injury. Supportive care for patients with PALI should be based on the need to maintain adequate oxygen and ventilator settings while reducing the potential for lung injury due to VILI or other causes. The clinical translational research on pharmacological approaches, including mitochondria-targeted drugs, remains extremely limited. Further research is needed to elucidate which patients benefit from therapeutic hypothermia.

Availability of data and materials

Not applicable.

Abbreviations

Aldehyde dehydrogenase 2

Acute lung injury

Acute respiratory distress syndrome

Cardiac arrest

Cardiopulmonary resuscitation

Computed tomography

Damage-associated molecular patterns

Extravascular lung water

Intracranial pressure

Intensive care unit

Interferon-gamma

Interleukin

Ishcemia-reperfusion

Lung ultrasound score

Mechanical chest compression

Mitochondrial DNA

Out-of-hospital cardiac arrest

Post-arrest lung injury
Post-cardiac arrest syndrome

Positive end-expiratory pressure

Pulse-induced contour cardiac output

Plateu pressure

Pulmonary vascular permeability index

Randomized controlled trial

Reactive oxygen species

Return of spontaneous circulation

Tumor necrosis factor-alpha

Target temperature management

Ventilator-associated lung injury

Ventilator-induced lung injury

Driving pressure

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Concept and design: KH. Drafting manuscript: YE. Acquisition and interpretation of the data: TA, EN, JH, KI, CEK. Critical revision of the manuscript: DJ, DMR, LBB, KH. All authors have read and approved the manuscript.

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The interplay between social environment and opportunities for physical activity within the built environment: a scoping review

Jens Høyer-Kruse 1 na1 ,
Eva Berthelsen Schmidt 1 na1 ,
Anne Faber Hansen 2 &
Marlene Rosager Lund Pedersen 1

BMC Public Health volume 24 , Article number: 2361 ( 2024 ) Cite this article

Metrics details

The association between social and built environments plays a crucial role in influencing physical activity levels. However, a thorough understanding of their combined impact remains unclear. This scoping review seeks to clarify the interplay between social environments and opportunities for physical activity within different built environments, with a particular focus on the implications of socioeconomic status and urban planning on physical activity participation.

We conducted a systematic literature search across several databases to identify studies exploring the associations between social factors, built environment characteristics, and physical activity levels. The inclusion criteria were studies published in English between 2000 and 2022, encompassing urban, suburban, and rural contexts. Thematic analysis was employed to categorise studies based on the specific aspects of the built environment they investigated (walking infrastructure, cycling infrastructure, parks and open spaces, and sports facilities) and the social determinants they examined.

A total of 72 studies were included in the review, illustrating a multifaceted relationship between access to physical activity opportunities and social determinants such as socioeconomic status, community engagement, and urban design. The findings highlight the significant role of socioeconomic factors and the quality of PA infrastructure in promoting or hindering PA across communities. Effective urban planning was identified as crucial in providing expanded physical activity opportunities, notably through more pedestrian-friendly environments, comprehensive cycling infrastructure, and accessible green spaces and sports facilities.

Conclusions

This review emphasises the significant impact of socioeconomic status and urban planning on access to physical activity opportunities. This underscores the necessity for urban planning policies to adopt an inclusive approach, considering the varied needs of different population groups to ensure equitable access to physical activity resources. Such strategies are crucial for public health initiatives aimed at enhancing physical activity levels across diverse community sectors, offering a potential avenue to alleviate health disparities associated with inactivity.

Peer Review reports

It is well known that physical activity (PA) is crucial to reducing chronic diseases and enhancing population health. Despite increased attention in recent years, the World Health Organization has revealed [ 1 ] that only one in four adults meets the recommendations for PA. The undeniable link between regular physical activity and overall well-being underscores the need for a comprehensive understanding of the factors influencing individuals’ engagement in PA. Two key determinants – the social environment and built environment – stand out as two of the most important factors in this intricate equation and have received increased attention in recent years [ 1 , 2 ].

The built environment is essential for PA opportunities, encompassing aspects of urban and architectural design, traffic density and speed, distance to and design of venues for PA, and crime and safety [ 3 , 4 ]. For example, previous studies have explored the impact of the built environment on PA, revealing how factors such as sports facilities, accessible parks, pedestrian-friendly paths, and community infrastructure can foster or hinder active lifestyles [ 5 , 6 , 7 , 8 ]. Similarly, social environment can be related to the level of PA, and the relationship between these two factors has been investigated in numerous studies [ 9 , 10 , 11 ]. Determinants of the social environment related to health include individual factors (age, gender, education, etc.), poverty and deprivation, social networks, political environment (e.g. policy), and background conditions, such as culture and economy [ 12 ]. In addition, the social environment can also be related to the landscape of the investigation, where several studies include the socioeconomic situation within the local area or neighbourhood, e.g. [ 13 , 14 ].

A recent study by Wang et al. [ 15 ] conducted a scoping review and examined the interaction between built and social environments and its impact on PA. They found that built and social environments influence PA and that consideration of people’s perceptions of their surroundings can provide further insight. This approach, focusing on broader determinants of health behaviour, is consistent with the socio-ecological perspective of health behaviour, where multiple factors interact with or influence PA, including aspects of work, physical and social environments, community conditions, and policies [ 16 ]. Combining these factors in the same study has become common practice, e.g. [ 2 , 15 , 17 , 18 ].

However, research on the interplay between social environment and opportunities for PA within the built environment is limited. In this regard, Brug et al. [ 19 ], stated in their study that ‘what we really need are not studies that highlight the importance of individual factors, social factors or built environmental factors in shaping nutrition and PA behaviours. We need more studies that integrate potential determinants at the environmental level and the individual levels.’ Drawing from this, our purpose is twofold: (1) to review the current literature to shed light on how social environment intersects with opportunities for PA within the four types of built environments inspired by McCormack and Shiell [ 20 ]: walking infrastructure, cycling infrastructure, neighbourhood parks, open spaces, and sports facilities; and (2) how the social environment combined with opportunities for PA within the built environment impacts PA levels. This scoping review differs from previous studies, e.g. [ 2 , 15 , 17 ], because despite its focus on PA levels, it also seeks to understand the differences in opportunities for PA within the four built environments and how they are influenced by social environment factors at the area and individual levels. Therefore, the included studies do not necessarily include measures of PA levels, but must, as a minimum, include measures to investigate the association between the built environment for PA and the social environment. Based on the significance drawn from this study, it can inform public health officials and planners.

Terminology of the main terms (physical activity, built environment and social environment)

Physical activity can be defined as ‘any bodily movement produced by skeletal muscle that results in energy expenditure’ [ 21 ]. In this framework, physical activity includes sports participation, active outdoor living, active transportation, recreational sports, and physical activity at work and during housework.

In this study, the built environment is defined as ‘the physical makeup of where we live, learn, work, and play – our homes, schools, businesses, streets and sidewalks, open spaces, and transportation options. The built environment may influence overall community health and individual behaviours such as physical activity and healthy eating’ [ 4 ]. This definition encompasses elements most pertinent to behaviours related to physical activity, including community design, public transport, built environment for active transportation (walking and biking), pedestrian safety, and other types of built environments in the local area, such as green areas, parks, open spaces, aesthetics and pleasantness, recreational facilities, and sports facilities [ 22 ]. Inspired by the categorisation of McCormack and Shiell [ 20 ], we divided the results of this study into four types of built environment: walking infrastructure cycling infrastructure, neighbourhood parks, open spaces, and sports facilities.

When examining the social environment, we were inspired by the social determinants of health described in the social ecological model of Gubbels et al. [ 16 ] and the definition of Blazer et al. [ 12 ] – meaning that besides our primary focus on factors of socioeconomic status (SES), including education, occupation, and income levels, this scoping review also encompasses a variety of individual factors (including age, gender, disabilities and ethnic background), social networks (including family and community), combined with policies, and the socioeconomic and cultural landscape of society with which individuals interact. For example, some of the included studies compared high-SES areas with low-SES areas, and some compared individuals with different ethnic backgrounds or income levels; that is, the social environment refers to the relationships, culture, and society with which individuals interact. Additionally, area density was used as a marker of the social environment.

In continuation of the description of social environment, in the results section, we further separate our results into individual-specific results and area-specific results focusing on either the individual factors (e.g. personal income, gender, age) of the social environment or societal or area factors (policies, density, socioeconomic, or cultural landscape of society, including area level income) of the social environment.

Identification of studies

Search for core concepts related to scope and databases.

To conduct this scoping review, we use the guidance for conducting systematic scoping reviews described by Peters et al. [ 23 ]. Initial scoping searches of the central issues of the research question (physical activity, social environment, and built environment) were conducted using several databases. The four databases with the most relevant preliminary search results were selected for the final search. The final literature search was performed using Global Health, Scopus, Sociological Abstracts, and SPORTdiscus. Studies published until 1 November 2019, included full English, German, Danish, Swedish, or Norwegian texts. There were no restrictions on publication year. The literature search was updated by 29th of August 2022 and pooled with the existing search results in Covidence (© 2022 Covidence). Duplicates were removed before review.

Search strategy

The search strategy we used for our study has been described in detail in another study by Pedersen et al. [ 24 ]. The search strategy was a mix of ‘free text words’ (searched in title, abstract and keywords) and ‘defined keywords’ (chosen from the Thesaurus lists of Global Health, Sociological Abstracts, and SPORTdiscus). Appendix 1 presents the entire search strategy.

Inclusion and exclusion criteria

The inclusion and exclusion criteria were set based on the purpose of this study, and the selected studies for review were required to meet one of the following two criteria:

Combining (a) PA in a broad understanding with (b) built environment opportunities for PA and (c) social environment factors (adult or elderly males and/or females aged 15 years or more and social environment factors as defined above).

Combining (b) built environment opportunities for PA and (c) social environment factors (adult or elderly males and/or females aged 15 years or older and social environment factors, as defined above).

In Fig. 1 , the visual representation regarding this is depicted. Within the delineated regions marked by crosses (+), articles will be included.

Visual presentation of the inclusion and exclusion criteria. Footnote Studies were included within the delineated regions marked by crosses (+)

Studies were excluded if they focused exclusively on specific types of physical activity (e.g. hang-gliding or parkour). Additionally, research focusing solely on particular ethnic minority groups (e.g. without comparison to the country’s majority population or similar groups) or specific disability groups (e.g. exclusively individuals with visual impairments) was also omitted.

Screening and selection

A total of 2,534 references were identified from the four databases. The search results were imported into the library software Endnote, and 641 duplicates were removed. After removing duplicates, 1,894 studies were uploaded to Covidence software (© 2022 Covidence), which was developed for systematic literature reviews. Title and abstract screening full-text screening was performed by two independent screeners (JHK and EBS). First, two authors screened 50 studies to internally validate the screening process. Subsequently, the same two authors screened the rest of the studies. In cases of disagreement, a consensus was reached between the two authors. Reasons for exclusion from the full text have been reported. Studies were selected based on the inclusion and exclusion criteria listed in Sect. 2.4. Through title and abstract screening, 1,694 studies were found to be irrelevant, and 200 studies were assessed as eligible for full-text screening, of which 128 were excluded for reasons (see Fig. 2 ). 72 studies were included for further analysis and reviewed by two authors. See Fig. 2 .

Flow chart of search results

Data extraction and interpretation of data

A structured spreadsheet was developed to identify common themes for extracting data from all studies included in the review. The data extracted included the year of publication, study location, study population and/or environment, study design, purpose, key findings, and focus related to the four types of built environments (walking infrastructure, cyclist infrastructure, neighbourhood parks, open spaces, and sports facilities) (Appendix 2). Using this spreadsheet, we summarised the data, followed by an interpretation of the patterns and trends shown in the literature. As this was a scoping review [ 23 ], formal evidence synthesis was not undertaken. Instead, we conducted a thematic analysis (described in the following section) to identify recurring themes across the studies. Subsequently, we developed a narrative synthesis through consensus meetings to describe, validate, and consolidate common findings and patterns in the results.

This review included 72 studies dealing with the association between social environment, PA, and opportunities for PA within the four types of built environments. Of these, 28 studies were from European countries, one from South Africa, five from Asia, 16 from North America, three from South America, and nine from Oceania. Studies that include more than one country count of 10 are mainly conducted across European, Oceania, and American countries. The country where we find most studies is England, followed by the USA and Australia (Table 1 ). The selected studies were published between 2002 and 2022 and included both quantitative and qualitative studies (Appendix 2).

Based on our thematic analysis, all 72 studies were categorised into four types of built environment, as shown in Table 2 . Some studies could be categorised into more than one category, which is why the total number of studies was greater than 72.

In studies exploring opportunities for PA within the four types of built environments in association with PA and social environments, a range of indices and measures were employed. The measurements of PA encompassed a comprehensive range of methods, including self-reported cross-sectional surveys, objective measures using accelerometers, qualitative interviews, observations, environmental assessments, interventions, and social determinants analysis. Methods employed to assess and measure various aspects of the built environments included walkability scores, geospatial/GIS analyses, audio-visual narratives and park audit tools. Finally, we also included a number of review studies which also spans various methods and measures relating PA.

Below, we provide an overview of the selected studies and their results organised by the four types of built environments. For each built environment, we further divided sections up between results that focus on area and individual specific variables.

Walking infrastructure (including street and pedestrian connectivity, land use, density, transit proximity and access, aesthetics and design)

Results focusing on area variables.

When looking into walking infrastructure in the context of societal or area factors of the social environment, and how it is related to opportunities for PA, we found four studies at the community level, indicating that high-SES areas tended to have higher walkability scores than low-SES areas [ 25 , 26 , 27 , 28 ]. A walkability score is a measure of how conducive an area is to walking and is influenced by the walking infrastructure factors. Having a higher walkability score indicate neighborhoods where walking is more convenient, safe, and enjoyable [ 20 ]. Jacobs et al. [ 29 ] did, however, find variations across their studies included in their review, with some studies highlighting that areas with higher SES tend to have superior walking infrastructure and greater amount of walking tracks, while other studies find the opposite. The presence and accessibility of walking facilities are generally identified as supporting walking [ 30 , 31 ]. In contrast to studies suggesting higher walkability scores in high-SES areas, an inverse relationship was found in studies by Choi and Yoon [ 32 ] and Conderino et al. [ 2 ]. The last study reported that on average, low-income neighbourhoods had higher walking scores than high-income ones. Notably, most white neighbourhoods generally had lower walk scores than other racial/ethnic majority neighbourhoods, except for the majority of black neighbourhoods, where tracts in lower income tertiles had the lowest walkability.

Perceptions within neighbourhoods also affect objective walkability measurements. Higher-income areas are often perceived as more aesthetically pleasing, with higher quality, fewer physical barriers to walking, and lower levels of crime and traffic [ 33 , 34 ]. Conversely, low-SES areas tend to have poorer perceived built environmental experiences [ 30 , 31 , 34 ]. Giles-Corti and Donovan [ 30 ] suggest that the quality of the built walking environment may be more important than the SES of the area of residence, as a correlate of walking behaviour. Other findings is also highlighting the built environmental factors, such as pedestrian bridges over large roads, well-maintain pavements, and illuminated walk-and-bike paths, as encouraging and crucial for walking behaviour [ 31 , 35 ].

Another aspect related to walking infrastructure opportunities for PA is the density of the area. Remote areas tend to have poorer walking and bicycle infrastructure, lower walkability scores, and less favourable structural attributes for PA [ 36 ]. Two studies found that areas with higher intersection density and connectivity, often urban, with multiple destinations and branched road networks, tend to promote walking and meeting PA recommendations [ 37 , 38 ]. The same result was observed among low-SES adults in a study by Christie et al. [ 39 ]. In contrast, Boone-Heinonen and Gordon-Larsen [ 40 ] found that higher landscape diversity was associated with higher PA, and for females, higher street connectivity was linked to lower PA. Furthermore, Isiagi, Okop, and Lambert [ 41 ] observed a negative association between intersection density and PA regardless of group. Wang et al. [ 42 ] also inversely observed a positive association between the built environment and PA in neighbourhoods characterised by low housing density, low road coverage, less land-use diversity (e.g. single land use of residence), high car dependency, poor access to public transport, longer distances to the city, and more green space coverage. Similarly, Frost et al. [ 43 ] found positive associations between aesthetics, pathways, safety from crime and traffic, parks, the ease of walking between destinations in the environment, and PA among adults in rural areas.

Furthermore, three studies found that living in high-SES areas is closely related to increased active transportation, higher PA levels, or more steps pr. day [ 35 , 44 , 45 ]. However, Seguin-Fowler et al. [ 44 ] found no association between the walk score and PA for those living in low-SES neighbourhoods. Isiagi, Okop, and Lambert [ 41 ] inversely found that residents in low-SES/high walkable neighbourhoods reported more transport-related PA compared to high-SES/low walkable neighbourhoods. Similar results were found by Besor et al. [ 46 ], who stated that areas characterised by lower-SES residents and a higher proportion of Arab minorities had better-performing health programmes (higher PA). Zang et al. [ 45 ] found that the PA of people living in low-SES areas was more dependent on the built environment, whereas the association was limited in high-SES areas. In studies of interventions in both high- and low-SES areas, a positive change in neighbourhood walkability was associated with increased PA, especially in adults in low-SES areas [ 27 , 47 , 48 ]. In a study by Clary et al. [ 27 ], improvements in walkability scores were mostly driven by increases in residential density and land-use mix. In contrast, Adkins et al. [ 49 ] concluded that the built environment has weaker effects on walking and physical activity in disadvantaged groups than in advantaged ones.

In summary, area-specific studies had different indications. Some studies found varying associations between walking infrastructure factors, there walkability score and PA (including transportation walking) [ 50 , 51 ], whereas others reported clear associations between higher walkability scores and increased PA across different SES areas [ 28 , 52 ]. Finally, Hillsdon et al. [ 53 ] found that most people engage in PA beyond an 800-metre radius from their homes, suggesting that neighbourhood characteristics alone may not predict PA levels.

Results focusing on individual variables

At the individual level, multiple studies have shed light on the interplay between determinants of the social environment, walking infrastructure, and PA. Gullon et al. [ 54 ] indicated that individuals with lower income levels tend to have more accessible walking destinations nearby. Furthermore, Christe et al. [ 47 ] revealed that the percentage change in walkability scores was positively associated with increased walking, particularly among those with lower income and education levels. Conversely, Cerin and Leslie [ 33 ] found that individuals with higher education and income may choose and afford to live in more PA-friendly built environments, including areas conducive for walking. Similarly, Andrade et al. [ 48 ] observed that individuals with higher incomes have better access to free or low-cost recreational facilities (including walking trails), a pattern that is also prevalent among those with higher education and more working hours. When examining the use of newly built walking and cycling infrastructure, Smith et al. [ 55 ] found that lower educational level and income, rather than ethnicity, were associated with reduced usage.

Dias et al. [ 56 ] explored the associations between built environmental factors (objectively and subjectively) and leisure walking among boys and girls with different SES backgrounds. For girls with low SES, access to services and shorter distance to parks and squares were positively associated with leisure walking. For boys, perceived environmental factors such as crime safety, land-use mix, neighbourhood recreation facilities, and places for walking are crucial factors for leisure walking. Another relevant study by Burton et al. [ 57 ] revealed that participants across income groups (low, intermediate, and high) place equal importance on similar factors, such as low crime, friendly neighbours, streetlights, and good paths, according to PA. Individuals with higher incomes only marginally emphasised these factors in their PA considerations. Similarly, Cleland et al. [ 58 ] found that individual factors, especially those of women with low SES, outweighed environmental factors. Specifically, higher PA levels among low-SES women were associated with interesting local walking opportunities and busy roads to cross during walking.

Cycling infrastructure (including biking paths, trails, path connectivity and quality)

At the area level, low-SES areas tend to have fewer biking paths compared to their high-SES counterparts [ 25 , 29 , 36 ]. Additionally, Darcy et al. [ 36 ] discovered that areas with more disadvantages, often residential areas, within the same local government area have lower quality PA opportunities than less disadvantaged areas. Remote areas also tend to have fewer functional PA opportunities (including walking and bicycle infrastructure) because of poorer structural aspects affecting streets and pathways [ 36 ]. The quality of infrastructure, including connected pathways, is considered crucial for transport-biking [ 31 ]. In Sweden, shortcomings in structural aspects, quality, and supportive features such as narrow bike paths, inadequate lightning, and concerns about personal safety were found to hinder cycling activity, especially for low-SES citizens [ 25 ]. This observation aligns with another Swedish survey study, indicating that active transport to and from school is nearly three times more common among adolescents (16–19 years) living in neighbourhoods with illuminated walking and bike paths than among those without [ 35 ]. The same study found that adolescents living in high-SES areas were 80% more likely to bike or walk to school than adolescents living in low-SES areas, and active transportation was 50% less common among adolescents from middle-SES areas than among those in low-SES areas.

At the individual level, a study conducted in London found that cycling for transportation was more common among white Britain (5.8% vs. 3.0% for ethnic minorities) and people with shorter transportation distances. After accounting for individual and area characteristics, this study also revealed that women and ethnic minorities are less likely to cycle. In contrast to England as a whole, cycling in London became increasingly concentrated among higher-SES groups over time, and increased infrastructure expenditure was associated with more cycling [ 59 ]. Similarly, a review by Smith et al. (2017) found in one study that newly built walking and cycling paths were used more by people with higher incomes, higher educational levels, and employment. [ 55 ]. Most of these patterns were consistent with Andrade et al. [ 48 ], who found that 24% of those with access to free or low-cost recreational facilities (including bicycle infrastructure) had a household income of at least USD 100,000 per year compared to 15.1% of those without access. Similar patterns were observed among those with higher educational levels and working hours.

In summary, a common feature across many studies is that access, length of the bike paths, and quality are associated with physical activity [ 25 , 35 , 46 , 48 ]. However, some studies investigating the association between cycle infrastructure, physical activity, and social environment have also found moderators pointing in different directions, leading to no clear conclusions [ 50 , 56 ].

Neighbourhood parks and open spaces

Two review studies indicated positive links between PA and neighbourhood parks, open spaces, and general green spaces, potentially reducing socioeconomic PA inequalities [ 31 , 43 ]. However, Giles et al. [ 51 ] presented a contrasting view on the limited benefits of green spaces in low-SES areas, highlighting the complexity of the relationship between green spaces and PA. Doiron et al. [ 26 ] observed that high-deprivation neighbourhoods had less access to greenness, affecting PA. Mears et al. [ 60 ] showed that residents from deprived areas in Sheffield made shorter, less active visits to green spaces. In contrast, Garrett et al. [ 61 ] found that access to green spaces significantly boosts PA through non-recreational activities, such as walking or jogging, particularly for low- and middle-income groups. Zhang et al. [ 62 ] underscores the importance of park safety in influencing adolescents’ PA, especially in low-income neighbourhoods, suggesting that perceived safety is a crucial determinant of park utilisation. This is complemented by Sun and Lu [ 34 ], who noted significant variations in safety perceptions across income groups affecting park use and the types of activities undertaken. Fontan-Vela et al. [ 63 ] and Schneider et al. [ 64 ] discussed how residents in higher-SES areas report more park use and fewer barriers, suggesting that these areas might offer better-maintained facilities and safer environments. Conversely, residents in lower SES areas cite limitations such as job constraints, perceived insecurity, and lack of suitable facilities, which hinder their park use and PA engagement. Wang et al. [ 42 ] revealed that neighbourhoods with more green spaces in high-SES areas correlate with higher levels of PA, emphasising the role of built environmental quality and accessibility in promoting active lifestyles. However, the proportion of green spaces also tends to be higher in high-SES areas than in low-SES areas, where the distance to and number of green spaces varies across SES areas according to the country in which the studies were conducted [ 29 ]. Fontan-Vela et al. [ 63 ] reported higher PA in parks within neighbourhoods with high socioeconomic status, citing fewer barriers than in lower-status areas. Schneider et al. [ 64 ] found equitable access to parkrun events across deprivation levels in England, but participation from local residents was low, highlighting the need for additional activation measures. Cohen et al. [ 65 ] in Los Angeles found that park use in low-income neighbourhoods was gendered, with women’s activities more sedentary compared to men’s. García-Pérez et al. [ 66 ] showed that park presence had little influence on women’s leisure-time PA. Finally, Jayasinghe et al. [ 67 ] highlighted the challenges in enhancing access to PA infrastructure and natural amenities across socioeconomic disparities.

A review indicated that SES impacts greenspace use for PA, with complex influences from built environment characteristics. Older adults with a higher SES engage more in PA in neighbourhoods with safe and pleasant built environments and abundant recreational facilities [ 68 ]. Anthun et al. [ 69 ] found no significant PA changes in a Norwegian suburb over three years, highlighting the importance of location, availability, and social spaces for motivation, with lower SES groups frequently using greenspaces, but dissatisfied with their quality. Clary et al. [ 28 ] linked daily moderate-to-vigorous physical activity (MVPA) to the distance to local parks in England, suggesting that travelling to parks boosts PA levels because of limited park facilities. A follow-up study by Clary et al. [ 27 ] found no evidence that improved greenspace access affects PA changes across SES groups. Gullon et al. [ 54 ] observed that low-income individuals had more green land cover nearby, but might perceive these areas as unsafe for PA, indicating socioeconomic disparities in PA engagement and greenspace perception. This is supported by Compernolle et al. [ 50 ], who stated that adults who perceive a greater number of destinations, such as recreational facilities, and those who live in neighbourhoods with more objectively measured aesthetic features, such as trees, green spaces, and parks, are more active.

Sports facilities

Two review studies initiated a discussion of area-specific results. Jacobs et al. [ 29 ] observed varied sports facility access across SES areas in 59 studies with no consistent associations found, whereas Frost et al. [ 43 ] identified positive associations between recreational facilities and PA in rural areas. Jayasinghe et al. [ 67 ] discovered good sports facility coverage in NW Tasmania, yet this did not lead to high sports participation, suggesting issues with facility visibility or activation. Eime et al. [ 70 ] reported a positive association between sports participation and facility availability in Australia adjusted for socioeconomic status and urbanisation, with higher participation in less urbanised regions. Hoekman et al. [ 71 ] explored rural-urban differences in sports participation in the Netherlands, highlighting the role of social environment in local sports engagement and the impact of facility diversity. Reimers et al. [ 72 ] found that gym availability significantly influenced rural girls’ sports participation in Germany, contrasting with urban girls and boys. Farrell et al. [ 73 ] linked the abundance of sports facilities in rural England to reduced physical inactivity, associating facility satisfaction with lower inactivity rates. Kokolakakis et al. [ 74 ] identified socio-demographic and economic factors as influencers of sports participation in England, downplaying the role of sports infrastructure in regional disparities. Billaudeau et al. [ 75 ] and Cereijo et al. [ 76 ] investigated the accessibility and quality of sports facilities in Paris and Madrid, finding mixed associations between SES and facility availability. Spanish studies by Pascual et al. [ 14 , 77 ] linked local economic resources with the number of sports facilities and PA, especially among older individuals and women. Hillsdon et al. [ 78 ] and studies from Asia [ 32 , 34 ] observed a positive association between SES and leisure amenity availability. Ferguson et al. [ 79 ] and Lamb et al. [ 80 ] showed that public transport access in low-income areas provides closer proximity to sports facilities, a difference nullified by car ownership. Panter et al. [ 81 ] and Hillsdon et al. [ 53 ] discussed how poor facility coverage in deprived English areas affects PA levels, with individuals often travelling beyond local areas for activity. Findings from Canada [ 82 ] and a review [ 38 ] indicate that women are more sensitive to local conditions and proximity to facilities. Australian research [ 18 , 33 ] has highlighted disparities in perceived access to sports facilities by income area, with psychosocial factors influencing PA more than built environmental factors. Pascual et al. [ 83 ] and Karusisi et al. [ 84 ] emphasised socioeconomic factors’ dominance over spatial in sports facility usage, with Boone-Heinonen and Gordon-Larsen [ 40 ] noting the impact of varied built environments and safety on young adults’ PA, affected by gender and urban density.

This section delves into how individual attributes such as age, gender, and socio-economic status influence sports facility utilisation, with Jacobs et al. [ 29 ] and Lee et al. [ 85 ] noting geographical and socio-demographic variations in access. Liu et al. [ 86 ] report lower SES and older individuals are less active in facility usage, highlighting complex factors behind participation. Ellaway et al. [ 87 ] found no significant link between sports facility accessibility and activity levels, factoring in SES and urbanization. Bergmann et al. [ 88 ] noted women and lower-income individuals in the South Region of Brazil frequently use outdoor gyms, suggesting mitigation of PA disparities. Gardam et al. [ 89 ] found that outdoor PA equipment in lower-income areas could reduce access disparities. Cutumisu and Spence [ 8 ] showed that objective access and personal factors, such as self-efficacy, impact PA adherence, with subjective perceptions of access not correlating with participation. Compernolle et al. [ 50 ] indicated that adults perceiving more neighbourhood destinations are less sedentary. Rovniak et al. [ 90 ] identified an ‘Active Leisure’ cluster, showing recreational facility availability boosts leisure-time PA. This is supported by Werneck et al. [ 91 ], who found that the presence of public PA facilities near a household was associated with higher leisure-time PA among all quintiles of income and educational level. Burton et al. [ 57 ] linked active lifestyles with social support, fewer activity barriers, and health issues among higher-income participants. Langøien et al. [ 92 ] highlighted the built environmental impact on PA for minority groups in Europe, emphasising the need for available, appropriate, and culturally sensitive facilities. Studies advocate comprehensive environmental improvements and increased PA knowledge and skills. An English programme providing free access to sports facilities, along with marketing and courses, significantly boosted gym and swim participation, particularly in disadvantaged groups [ 93 ].

Table 3 is a result from our narrative synthesis and summarises and integrate our research findings on the interplay between PA, the social environment, and opportunities for PA across four types of built environments: walking infrastructure, cycling infrastructure, neighbourhood parks and open spaces, and sports facilities. In synthesizing the findings of 72 studies, this narrative synthesis highlights the most typical results, focusing on the common themes and patterns that emerged across the built environments. By distilling these studies into a cohesive summary, we provide a comprehensive overview of the main trends and outcomes. However, due to the broad scope and the necessity to concentrate on overarching themes, some nuanced details and specific variations within individual studies are not fully represented, meaning that there will be studies in each of the built environments that can show contradictory results.

This scoping review examines the intricate association between the social environment and opportunities for PA within the built environment and supports our study’s initial assertion that both factors significantly influence PA levels. The diverse outcomes observed in relation to walking infrastructure, cycling infrastructure, neighbourhood parks, open spaces, and sports facilities emphasise the intricacy of these relationships. Our study’s dual focus on area- and individual-specific influences, as outlined in Table 3 , offers a distinct perspective for understanding how both social and built environmental attributes function as critical facilitators or barriers to access to PA opportunities and engagement in PA.

Given the global imperative to combat sedentary lifestyles and their associated health risks, our discussion delves into the implications of our findings in a broader context of health promotion. Moreover, we address the notable disparities in PA opportunities and engagement across social environment variables, underscoring the importance of targeted interventions that are sensitive to both the built environment and individual determinants of PA.

Area-specific and individual-specific influences on PA engagement

As we dissect the implications of our findings, it becomes increasingly evident that the determinants of PA are not monolithic but rather a tapestry of intertwined area-specific and individual-specific factors. First, area-specific results revealed the profound impact of the built environment on PA opportunities. Walking and cycling infrastructure and the availability of parks and sports facilities do not uniformly benefit all community members. Instead, their influence is modulated by the socioeconomic fabric of neighbourhoods, revealing a gradient of accessibility that mirrors societal inequities.

However, several studies in our review also investigated the subjective perceptions of accessibility, connectivity, and built environment quality [ 56 , 58 ], which made it clear that the built environment’s impact on individual behaviour cannot be fully explained by objectively measured indicators. The individual-specific results illuminate the equally pivotal role of personal factors, from socioeconomic status to perceptions of safety and aesthetics, in shaping PA behaviour. These findings underscore the subjective nature of PA engagement and the understanding of opportunities for PA, in which personal motivations, perceptions, and barriers play a role against the backdrop of available environmental resources, which is also supported by the findings of Wang et al. [ 15 ], (2023).

The mutual dependency between personal factors and physical environment underscores the need for a comprehensive strategy to advance PA. This strategy should encompass both concrete and abstract factors that shape a person’s willingness to engage in PA. These factors align with those outlined in socioecological models, which include policy and environment (e.g. neighbourhood safety), sociocultural factors (e.g. community support for physical activity), and personal beliefs (e.g. perceptions of physical activity) [ 16 ]. Such factors are pivotal in shaping socioeconomic disparities in PA behaviour. In particular, the impact of safety perceptions and aesthetic appeal on walking activities underscores their critical role, often surpassing the influence of the physical setting on PA engagement.

Addressing social environment disparities

The disparities in physical activity underscored by our findings highlight the complex interplay between social environmental factors and access to PA-enhancing environments. Area-specific variables revealed a clear contrast in the availability and quality of walking and cycling infrastructure, neighbourhood parks, open spaces, and sports facilities across high- and low-SES areas. Our analysis indicates that high-SES areas typically enjoy superior walking infrastructure, more extensive and better-maintained cycling infrastructure, and greater access to parks and sports facilities. This built environmental privilege translates into higher levels of PA among residents, underscoring the need to shift towards built environmental equity. Urban planning and policies must prioritise the development and maintenance of PA infrastructure in low-SES areas, ensuring that all community members have equal opportunities to engage in health promoting physical activities.

Our results on the individual-specific variables confirm this association, as we find that individuals with low income and educational levels have less access to facility opportunities for PA across the four types of built environments. At the same time, it also highlights how lower income and education levels mostly correlate with reduced utilisation of opportunities for PA within the built environment. Most often, it is also the lower SES groups that have poorer perceptions of their opportunities for PA, their safety, aesthetics, and availability, pointing towards a multifaceted challenge that requires nuanced solutions. The influence of individual-specific variables on PA participation and PA opportunities thus cannot be overstated. Consequently, interventions aimed at increasing PA and opportunities must address these perceptions directly. Community engagement initiatives involving residents in the planning and maintenance of PA facilities can enhance the sense of ownership and safety. Moreover, programmes designed to boost social support for PA within communities can help overcome individual barriers and encourage more residents to lead more active lifestyles; physical features such as lightning and aesthetics can improve the perception of opportunities to engage in PA within the local environment, especially in low-SES areas.

Suggestions for future research

This review indicates that many researchers have focused on the relationship between social and built environments for PA; however, more literature focusing on individual perceptions of opportunities for PA within the built environment across different social environment indicators is needed. Further exploration of the subjective perceptions of accessibility, aesthetics, connectivity, and built environment quality across different social environment indicators (individual- and area-specific factors) can provide deeper insights into how individuals perceive their environment, how these perceptions influence their PA behaviours, and how an understanding of how multiple factors intersect to shape PA behaviours can inform more targeted interventions.

Strengths and limitations

The strengths of this study include a comprehensive analysis of the interaction between the determinants of the social environment and opportunities for PA within built environments, highlighting the importance of equitable access to recreational facilities. This underscores the role of urban planning in promoting health through infrastructure. However, it faces limitations, such as potential biases in self-reported physical activity data, lack of longitudinal data to establish causality, absence of higher-quality systematic reviews articles included on the theme, and possible oversimplification of the complex interplay between socioeconomic factors and physical activity behaviours.

Despite the potential to advance our understanding of global health disparities, when investigating the interplay between the social environment and opportunities for physical activity across countries, we must recognise that there are limitations that should be considered. When comparing results across countries, there can be various cultural norms and values regarding PA. For example, what constitutes acceptable or accessible forms of activity can vary greatly, influencing how the determinants of the social environment interact with built environments to shape physical activity opportunities. Furthermore, differences regarding the socioeconomic context, urban planning disparities, data availability and quality, policies, environmental context, and the like, can make it challenging to generate meaningful insights into the complex relationship between social- and built environments, and physical activity outcomes on a global scale. This could be differences related to density and diversity across countries in relation to SES-factors. In the US, higher SES, for example, often correlates with suburban areas that have lower walkability scores due to less density and diversity. These areas tend to have higher levels of PA despite the lower walkability scores, possibly due to greater access to private facilities and transportation, where in European studies, this association might be different and show other patterns.

This review illuminates the complex interplay between social and built environments that affects opportunities for physical activity (PA) and the impact on PA levels. This highlights the significant role of socioeconomic factors and the quality of PA infrastructure in promoting or hindering PA across communities. Notably, disparities in access to PA resources underscore the need for equitable urban planning and public health interventions.

This study’s insights are crucial for developing targeted strategies that address both physical and social barriers to PA. Advocating inclusive and accessible PA facilities calls for a unified approach to enhance PA levels universally, emphasising the importance of addressing socioeconomic disparities in PA access.

This review advocates integrated efforts to ensure equitable access to PA opportunities, aiming to support health and well-being for all, regardless of socioeconomic status. These findings are vital for informing more effective public health policies and urban planning strategies that foster a more active and healthier society.

Data availability

All data have been published as supplemental materials and collected from published articles.

Abbreviations

Physical activity

Socioeconomic status

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Acknowledgements

The authors would like to thank our colleagues in the ´Moving Denmark´ project that contributed to the literature review: Lars Breum Christiansen, Karsten Elmose-Østerlund, Thomas Viskum Gjelstrup Bredahl, Henriette Bondo Andersen, Mette Brandt Eriksen, Birgitte Westerskov Dalgas and Bjarne Ibsen.

This research is part of the ‘Moving Denmark’ project, which was co-funded by the Nordea Foundation (grant number 02–2019-00025). The Nordea Foundation did not influence the collection, analyses, or interpretation of data.

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Jens Høyer-Kruse, Eva Berthelsen Schmidt & Marlene Rosager Lund Pedersen

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MRLP, JHK, and AF conceived the study. AF created the search strategy and conducted the search within the selected databases. Subsequently, EBS, JHK, and MRLP screened all studies, after which EBS and JHK determined the studies to include and exclude based on the predetermined inclusion and exclusion criteria for this study. MRLP and AF wrote the methodology section (including Appendix 1 ), while EBS and JHK authored the results section (including Appendix 2 ), with each responsible for writing the results for two built environments. Finally, JHK and EBS composed the discussion and conclusion. All authors have read and provided comments on the manuscript drafts and approved the final manuscript.

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Høyer-Kruse, J., Schmidt, E.B., Hansen, A.F. et al. The interplay between social environment and opportunities for physical activity within the built environment: a scoping review. BMC Public Health 24 , 2361 (2024). https://doi.org/10.1186/s12889-024-19733-x

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The open innovation kaleidoscope: navigating pathways and overcoming failures

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Maral Mahdad ORCID: orcid.org/0000-0001-6612-5664 1 &
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1 Introduction

In two decades of open innovation, the landscape resembles a kaleidoscope where numerous facets and aspects intersect. This gives rise to a dynamic phenomenon marked by opportunities as well as challenges (Chesbrough 2004 ). The concept of open innovation introduced by Henry Chesbrough in his seminal book (Chesbrough 2003a , b ) has reshaped the way organizations innovate and revolutionized how they collaborate, compete, and adapt in a rapidly evolving environment. Over the past two decades, OI has transformed the boundaries of theoretical constructs and scholarly research. It has embedded itself in the strategies, tactics and operations of businesses, governments, and institutions (Holgerson et al. 2022 ; McGahan et al. 2021 ; Rexhepi et al. 2019 ; West and Bogers 2017 ). However, as the open innovation landscape unfolds, it reveals a complex interplay of elements, factors and levels of analysis that require a panoramic view—a kaleidoscopic examination—to capture different pathways that characterize the spectrum. In addition, these complexities depend on a range of contextual elements in the firm and the business environment (Madanaguli et al. 2023 ).

Open innovation has proven transformative in reshaping industries (Christensen et al. 2005 ), changing competitive business environments (Bacon et al. 2020 ), and fostering opportunities for companies efficiently practicing OI (e.g. Caputo et al. 2016 ; Majchrzak et al. 2023 ). Yet, for all its promise, open innovation comes with challenges (Dabic et al. 2023 ; Madanaguli et al. 2023 ; Chaudhary et al. 2022 ). As it extends from idea generation to scalability it encompasses process-related challenges (Madanaguli et al. 2023 ). The transition from collaboration to “coopetition” introduces strategic challenges (Corbo et al. 2023 ; Gast et al. 2019 ; Kallmuenzer et al. 2021 ; Xue et al. 2023 ). Open innovation is marked by complexities and ambiguities. As organizations explore this terrain, they encounter the shadows of potential failures (Cricelli et al. 2023 ). Recognizing that the potential of a kaleidoscope lies in its ever-shifting patterns, we understand that open innovation, requires a multifaceted lens to comprehend its full potential. Creating an unbiased panoramic view through diverse literature review methods advances academic discussion and fuels our motivation. This view provides a solid foundation for our analytical exploration along research pathways (Kraus et al. 2022 ). In our research, we use topic modeling with machine learning algorithms (Hannigan et al. 2019 ) to enable the unbiased view over the two decades of OI research and increase replicability and transparency. Thereby, we incorporate extra dimensions of openness and soundness to the outcomes of traditional systematic reviews (Kraus et al. 2020 ). We add a novel abductive interpretative reasoning layer (Walton 2014 ) for comprehensively understanding open innovation failures and risks across ten open innovation pathways. In doing so, we aim to equip organizations and scholars with a well-rounded perspective that guides their strategic decision-making in practicing OI. Therefore, our research answers the question: What predominant topics have been explained by recent scholarly discourse in open innovation, and how are failure mechanisms within these topics delineated across the micro, meso, and macro organizational levels?

This multi-level system perspective was originally inspired by “Coleman’s Boat” (Coleman 1994 ), which aims to bridge macro and micro levels by pointing out the key components needed to develop robust theory. In management research, the macro level often encompasses the system, economy, industry, and society, while the micro level refers to individual and behavioral attributes (Cowen et al. 2022 ). In this context, meso-level refers to firm-level outcomes. Additionally, it is well-documented that the phenomenon of open innovation spans multiple levels, and our approach to investigating it at different levels aligns with prior literature (e.g., Bogers et al. 2017 ).

The field of open innovation, though extensively researched, continues to suffer from a fragmented understanding of its diverse and evolving nature, characterized by multiple pathways and shifting narratives. For example, Bertello et al. ( 2024 ) extensively reviewed the literature of the field. They showed that some scholars have attempted to leverage well-established theories such as a resource-based or knowledge-based view of the firms, while others have begun to renew the theoretical foundation to generate new discussions. These endeavors have enriched the field of open innovation. However, they have also increased the heterogeneity of its theoretical foundations, making it more challenging to develop coherent theories in new empirical contexts. This drives our first motivation to conduct a comprehensive examination and synthesis of open innovation research. We aim to shed light on its historical evolution and chart the path for future academic inquiries through topic modeling, a machine learning technique that uses natural language processing. Topic modeling offers a dynamic, comprehensive method for discerning hidden data patterns, surpassing traditional systematic literature reviews (SLR) in revealing emerging trends and adapting to shifts in research (Kraus et al. 2022 , 2024 ; Brem et al. 2023 ; Hannigan et al. 2019 ). Its aptitude for processing extensive datasets and the use of visualization tools simplifies the understanding of complex topic relationships (Hannigan et al. 2019 ). Objective and reflective analyses become fundamental for assessing the existing knowledge base, pinpointing knowledge gaps, and evaluating the efficacy and productivity of open innovation research This benefits both the practice and academic communities (Randhawa et al. 2016 ) and ultimately moves them forward. In fact, topic modeling techniques offer researchers the opportunity to create multi-dimensional artifacts like differentiation and novelty (Hannigan et al. 2019 ). However, its full potential is realized when an iterative and interpretive approach is integrated into the analytics. The novelty of our research comes from using interpretative thematic analysis to qualitatively examine topics identified by topic modeling techniques through the lens of failure. The diversity of OI pathways plays a pivotal role in shaping the identity and avenues of open innovation research and practice, reflecting its core concepts, paradigms, recognition mechanisms, and directions (Radziwon et al. 2022 ).

The choice of failure as a lens to examine open innovation (OI) challenges has recently received attention in OI research, although it has not been specifically carved into various OI pathways. Failure as an analytical lens was selected for two main reasons. First, the lack of studies on the downsides of OI represents a significant gap, potentially giving the misleading impression that OI is a cure-all for firms’ innovation challenges (Greco et al. 2022 ). Second, the need for alternative review techniques is necessary to gain a fine-grained understanding of open innovation failure (Chaudhary et al. 2022 ).

Our research therefore encompasses two decades of open innovation, offering a comprehensive analysis of ten critical pathways within the OI domain. In addition, it illustrates the nuanced failure mechanisms at micro, meso and macro levels that could negatively affect OI processes. Furthermore, it provides a snapshot of the current landscape and proposes prospective trajectories for the evolution of OI research based on the controversies in the field.

2 Methodology

This research improves topic modeling by integrating interpretative analysis commonly found in systematic literature reviews. This is in line with methodologies emphasized by leading experts like Kraus et al. ( 2022 ). Using an in-depth literature review conjoined with the procedure of topic modeling, the present research offers a comprehensive and categorized view of existing literature pertinent to open innovation within business and management domain. The approach combines a detailed literature review with topic modeling to offer a comprehensive perspective and categorization of existing literature on open innovation within the business and management domain. Our methodology follows a structured and transparent process, adhering to best practices for conducting systematic literature reviews (SLRs) as outlined in recent literature (Kraus et al. 2024 ). Specifically, the guidelines provided by Dhiman et al. ( 2023 ) and Rammal ( 2023 ) were instrumental in shaping our approach, ensuring that our review is thorough, systematic, and replicable. Additionally, recent studies have effectively utilized the SLR methodology to explore various aspects of management research, demonstrating its versatility and robustness. For instance, Sauer and Seuring ( 2023 ) employed an SLR to develop a comprehensive guide for conducting literature reviews in management research, emphasizing key decisions and steps. Similarly, other researchers have applied SLRs to investigate diverse topics, such as supply chain management (da Silva et al. 2024 ), absorptive capacity (Pütz et al. 2024 ), crowdsourcing and open innovation (Cricelli et al. 2022 ; Carrasco-Carvajal et al. 2023 ), the organizational, environmental, and socio-economic sustainability of digitization (Chopra et al. 2024 ), further validating the methodology’s applicability and relevance in our study.

Our methodology involves four key steps as described in Table 1 : data collection, topic modeling, topic exploration, and topic interpretation with failure as a lens. In the data collection phase, we employed a comprehensive search strategy across Web of Science, to gather relevant peer-reviewed articles. We then utilized Latent Dirichlet Allocation (LDA) for topic modeling, which allowed us to identify and categorize latent topics within the literature systematically (Blei 2012 ; Brem et al. 2023 ). The subsequent exploration and interpretation of these topics involved a critical analysis that integrates insights from the literature on systematic reviews in management research, drawing on established frameworks to ensure a comprehensive and nuanced synthesis. This robust methodological framework ensures that our study not only maps the existing body of knowledge but also identifies key gaps and future research directions in the field of open innovation, as emphasized by Rana et al. ( 2023 ), Rammal ( 2023 ) and Baltazar et al. ( 2023 ) (Fig. 1 ).

Overview of the research methodology

2.1 Data collection

To ensure a comprehensive examination of the open innovation literature, our primary data source was the Web of Science Core Collection (WoSCC) database. The WoSCC is widely recognized for its extensive coverage of high-quality research articles across various disciplines. WoS is one of the most comprehensive and widely used citation databases in the academic community. It covers more than 13,610 journals across all disciplines (Singh et al. 2021 ; Falagas et al. 2008 ). To find most relevant articles in the field, we used a search string based on Gao et al. ( 2020 ). Additionally, in recognition of the first article in this domain written by Chesbrough ( 2003a , b ), we refined our search to encompass articles from 2003 to 2023 (Gao et al. 2020 ; Kovacs et al. 2015 ). The detailed search criteria and keywords employed are presented in Table 1 .

The initial retrieval yielded a sample of 2,551 articles. Recognizing the importance of data quality in conducting rigorous research, we undertook a thorough data-cleaning process. This involved supplementing missing abstracts, removing duplicates, and discarding articles without abstracts. After this rigorous cleaning process, we were left with a final sample of 2,537 unique articles These formed the basis for our subsequent analyses.

2.2 Topic modeling

After finalizing the collection of relevant articles, we explored topic modeling, a method essential for uncovering hidden thematic patterns in large volumes of text (Blei 2012 ). This technique offers an objective perspective on dominant trends and provides a detailed understanding of the subject matter. In natural language processing and machine learning, a topic model is a statistical method for determining the “topics” in a set of documents. Latent Dirichlet Allocation (LDA) can uncover hidden semantic structures and topics in a large body of unstructured textual data using natural language processing, machine learning, and statistical algorithms (Blei et al. 2012 ; Wang and Blei 2011 ).

There are several notable advantages to using topic models. They rest on mathematically robust principles, elucidating the intricate dynamics of document generation. Moreover, they operate without needing prior categorization or labeling of documents, enabling an autonomous and expert-independent analysis. This autonomy extends to their capability to systematically organize and summarize vast swathes of documents, making them invaluable in text mining applications (Lee and Kang 2018 ). These attributes have led to an increased interest in topic models, finding successful applications across diverse text mining activities (Yan 2014 ). Several researchers in management studies have employed topic modeling techniques. Specifically, these approaches have been explored in fields such as marketing (Mustak et al. 2021 ; Amado et al. 2018 ), technology and innovation management (Lee and Kang 2018 ), information systems (Jeyaraj and Zadeh 2020 ), crisis innovation (Brem et al. 2023 ), open innovation (Lu and Chesbrough 2022 ), and human resource management (Thakral et al. 2023 ).

Before conducting topic modeling to identify relevant topics, some pre-processing procedures were required. Both the title and abstract of the articles were amalgamated to serve as the model’s input. This decision was based on the rationale that titles encapsulate the most representative terms, and the abstract delineated the study’s context, objectives, methodologies, and conclusions. We employed several steps to create a corpus that was used for topic modeling. In the initial phase, the entire text was divided into sentences and the sentences into the tokens (tokenization). Punctuation and numerical characters were subsequently excluded, and all characters were converted to lowercase. The subsequent step entailed the removal of words with fewer than three characters, including the extension of this process to eliminate structural words commonly found in abstracts, such as “aim,” “purpose,” “study,” “framework,” and “effect” (stop words). Next, word bigrams were created to link words that co-occur frequently. For instance, the combination of “business” and “model” was treated as “business_model”. Using lemmatization algorithms, words were transformed into their root forms to reduce dimensionality without loss of generality. For example, the term “industry” could manifest as “industry” or “industries” as a noun, “industrial” as an adjective, “industrialize,” “industrializes,” or “industrialized” as a verb, and “ndustrially” as an adverb. This was followed by word-stemming procedures that streamlined these words to their base forms, exemplified by the stemming of various forms of the term “industry” to “industri”. In addition, we removed all terms that occurred fewer than five times across all documents or that appeared in more than 70% of records. The final step in preprocessing was to convert the documents into a bag-of-words format. In this model, each document was depicted as a vector consisting of an unsequenced set of words. All of these tasks were implemented using gensim v. 3.8.3 (Rehurek and Sojka 2010 ), NLTK v. 3.7, and spaCy v. 3.0.0. (Honnibal et al. 2020 ).

We employed Latent Dirichlet Allocation-LDA (Blei et al. 2003 ) for topic modeling and used the Machine Learning for Language Toolkit (MALLET) for implementation. MALLET is an open-source Java-based machine learning package known for its sophisticated tools for statistical natural processing, document classification, sequence tagging, numerical optimization, and topic modeling, among others (McCullum 2002 ). One of its primary advantages is its scalable and efficient implementation of Gibbs sampling. Additionally, it provides efficient methods for document-topic hyperparameter optimization and has built-in tools for inferring topics on unseen documents using trained models. The MALLET tool is multi-threaded and optimized for performance on a single machine. However, it is worth noting its limitations. It can be memory-intensive, and handling extremely large datasets might lead to frequent garbage collection. As a result, it might not be scalable for massive datasets and can be challenging to scale across multiple nodes of a cluster (Sukhija et al. 2016 ). Despite these limitations, MALLET's robust features and efficiency, combined with the size of our data, made it a suitable choice for our study’s dataset and requirements.

Determining the optimal number of topics is a significant challenge in topic modeling. Researchers often use several measures, such as coherence and perplexity, to pinpoint the optimal number of topics. Although the perplexity measure is commonly used for this purpose (Jeong et al. 2019 ), there are no standard packages for its computation in MALLET. To address this issue, we used the topic coherence score to determine the optimal number of topics. This metric measures the quality of a given topic model by computing the semantic similarity between its highest-scoring terms. We used two specific coherence measures: c_v and u_mass. The c_v measure, rooted in a sliding window approach, uses a one-set segmentation of top words and indirect cosine similarity for confirmation. In contrast, u_mass is based on document co-occurrence counts and a one-preceding segmentation, confirming using the measure of log conditional probability (Röder et al. 2015 ). For c_v, higher values indicate better topic coherence, while for u_mass, values closer to zero suggest peak coherence (Röder et al. 2015 ) Our analysis employed both the c_v and u_mass measures. While some studies adopt statistical approaches, others rely on subjective analysis, where experts evaluate the appropriateness of number of topics (Madzík et al. 2023 ). Subsequently, we also engaged expert opinions to validate and refine our topic selection based on the coherence scores. As shown in Fig. 2 , the coherence scores, when plotted against the number of topics, provide insightful observations. The c_v scores consistently hover around their peak within the range of eight to 13 topics, reaching a peak of 0.3991 at 10 topics. This consistency suggests a stable and coherent representation of the data within this range. Meanwhile, the u_mass score indicates two topics as optimal, with scores closest to zero. However, such minimalistic categorization could potentially oversimplify our dataset, neglecting its inherent complexity and nuances. Within the range of eight to 13 topics, the u_mass scores are less negative, hinting at a semantic closeness and meaningful topic delineation. Given these findings, and for a more comprehensive perspective, we deemed it prudent to explore the topic range of eight to 13, striking a balance between coherence and detailed representation. A thorough evaluation of these topics subjectively led us to determine the optimal topic number at 10, marked by a c_v score of 0.3991 and an u_mass score of − 2.154.

Topic coherence scores

2.3 Topic exploration

Upon building the LDA model with 10 topics, we employed various techniques to further explore these topics. We visualized topics using the word_cloud library v. 1.8.1, where the size of each word within a specific topic is proportionate to its frequency within that topic. Additionally, we used the PyLDAvis library v. 2.1.2 for topic interpretation, based on the 10 topics identified earlier (Sievert and Shirley 2014 ). PyLDAvis facilitates topic visualization and offers deeper insights through its unique inter-topic distance mapping. This tool computes topic centers using Jensen–Shannon divergence (JSD) and calculates inter-topic distances using multidimensional scaling. It effectively maps multi-dimensional topic distances onto a two-dimensional plane, providing a spatial representation of topic proximity.

Subsequently, we also normalized the weight of each topic per year to analyze the annual changes in open innovation research. We used Mann–Kendall (MK) test. The null hypothesis in this nonparametric test is that the sample data are independent and randomly distributed (Hamed and Rao 1998 ). We used the pyMannKendall python package Version 1.4.2, which is a pure Python implementation of non-parametric Mann–Kendall trend analysis (Hussain and Mahmud 2019 ). However, before using the Mann–Kendall test, we needed to confirm that autocorrelation was not present in our data, as it could bias the Mann–Kendall results. For this, we employed the Durbin–Watson statistic, which tests for serial correlation between errors (Neeti and Eastman 2011 ). The Durbin–Watson test produces values that range from zero to four. A value close to two suggests no autocorrelation, while a value near zero indicates positive autocorrelation. Values near four imply negative autocorrelation. Our results shows that all values are below two, indicating the presence of positive autocorrelation in the data. In this case we used Hamed and Rao’s modification test to identify trends in topics (Hamed and Rao 1998 ). Upon further investigation, we noticed fluctuations in the data before 2002. To mitigate the potential biases these fluctuations might introduce to our trend analysis, we excluded data prior to 2002. After this adjustment, we recalculated the Mann–Kendall test to discern trends in the topics. To classify the most pertinent documents for each topic, we extracted the dominant topic for each document in our corpus. Using our LDA model, we assigned each document to the topic that had the highest contribution in that document. The “Dominant Topic” in our dataset is determined by identifying the topic number with the highest percentage contribution for that document. This is recorded as “Contribution %,” which signifies the weight of the topic in that particular document. This method ensures that each document is associated with its most relevant topic. It streamlines the process of analyzing journals and other sources based on topic dominance.

2.4 Topic interpretation and failure as a lens

Following the identification of topics, we embarked on an interpretive analysis of each one. Every article in our sample was categorized based on its predominant topic. Subsequently, to contextualize and synthesize the most pivotal contributions, we reviewed the articles with a high percentage of contribution to their associated topic. Our initial approach involved a thorough examination of the abstracts of articles with significant contributions to each topic. This facilitated the selection of works serving as exemplars. The representativeness of these chosen articles was cross-verified against the topic-related terms for accuracy. Upon this validation, we investigated these selected articles with other significant contributions within the same topic domain. As a culminating step in our analytical process, after an exhaustive review of articles within each topic, we assigned descriptive failure labels to every topic to encapsulate its essence. We adopted a failure lens for the selected articles in each topic, based on the rationale that these papers investigate OI cases representing constraints, limits, risks, or challenges for OI implementation. We then categorized the associating level as micro, meso, or macro, and included theoretical and conceptual papers in this analysis.

We collected 2,537 articles from the Web of Science database from 2003 to 2023. Figure 3 shows the number of publications in the field of open innovation from 2003 to 2023. The data shows a steady increase in the number of publications over time, with a peak in 2022 with 354 articles, followed by 276 articles in 2021 and 259 articles in 2020. The data suggests that open innovation is a rapidly growing field of research, with a high level of interest from the academic community.

Growth of scientific publications on open innovation (Web of Science). Note : The decrease observed in 2023 can be attributed to the year not being complete at the time of analysis

Table 2 provides a detailed breakdown of the most frequently cited journals within the realm of open innovation research in business and management. “Technological Forecasting and Social Change” holds a prominent position with 133 publications and a cumulative citation count of 5,239, translating to a citation impact of 39.40. “R&D Management” and “Technology Analysis & Strategic Management” closely follow with 121 and 91 publications, amassing 10,084 and 1,748 citations, respectively. Notably, “Research Policy” has a high citation impact of 130.87, indicating its seminal contributions to this field.

3.1 Topic modeling results

The use of topic modeling enabled us to uncover latent semantic structures within the unstructured textual data we collected. Through this technique, we identified a model consisting of 10 distinct pathways, which effectively encapsulated a comprehensive range of OI-related subjects. The word-cloud analysis of the topic modeling outcomes, presented in Fig. 4 , visually portrays the word distribution within the eleven identified topics.

Word cloud of open innovation topics in business and management research

Table 3 provides an overview of the key terms associated with each topic, along with the corresponding count of documents and the cumulative citation count. These findings collectively underscore the diverse array of topics that span across various academic disciplines.

In this comprehensive examination of ten pivotal topics in the field of open innovation research, we present our result in each pathway implementing a dual analytical framework. Initially, we describe the principal attributes inherent in each pathway, subsequently progressing to an abductive exploration that unveils the associated failure mechanisms embedded within the open innovation landscape. This multifaceted analytical approach extends across the micro (individual), meso (organizational), and macro (system) levels of analysis, providing a holistic view of OI failures in these pathways.

3.1.1 Pathway 1: value creation and capture in OI setting

Main features :

Within the open innovation landscape, the emergence of collaborative ecosystems stands out as a pivotal theme. Central to this pathway is the intricate interplay between business models, ecosystems, and networks. Specifically, the concept of a business model as a tangible construct takes the spotlight. In open innovation contexts, business models play an indispensable role in delineating the generation and capture of value within collaborative networks. This pathway also introduces the collaborative business model concept, underscoring the significance of co-creating and capturing value that extends beyond the confines of a single firm. Furthermore, it emphasizes the imperative of network alignment and the need for well-structured, interconnected networks. These facilitate the effective creation and capture of value at a macro level. Notably, this pathway displays strong linkages with sustainability transition research. It sheds light on the role of value creation and capture mechanisms in driving sustainability-oriented open innovation.

Failures in value creation and capture in OI:

At the micro level, we found that issues related to learning, attitudes, and organizational culture can slow down value creation processes. At the individual level, resistance to change hinders creative processes related to co-creating values with other organizations. At the meso level, organizational capabilities play a pivotal role in determining the effectiveness of value capture mechanisms. Challenges such as information asymmetry, limited rationality, and opportunistic behavior can impede the realization of value from collaborative efforts. Furthermore, the uneven distribution of intellectual property (IP) ownership can lead to disputes that affect value capture mechanisms, often resulting in wasteful litigations. Our findings indicate that, on the macro level, we could not extract any factors. External factors, such as regulatory, economic, and cultural aspects, that impact how value is created and shared in the broader context, need to be further examined.

3.1.2 Pathway 2: managing the OI process

Main features:

The second pathway in our exploration phase leads to the management of open innovation processes. It includes a broad range of sub-themes, including empirical case studies on OI processes involving SMEs and LEs. An integral aspect is the emphasis on the management of knowledge flows, ensuring that valuable insights and expertise circulate efficiently in open innovation ecosystems. Furthermore, this pathway exhausts the concept of the “Liability of Smallness,” which is discussed in the context of SMEs and the unique challenges they face in the OI paradigm. Additionally, this pathway deals with the role of discovering market opportunities and the execution of collaborative research and development (R&D) efforts as two domains in managing OI processes. Additionally, assessing the strategic fit of and with partners plays a pivotal role in managing OI process.

Failure in managing the OI process:

At the micro level, individual networks may fail to contribute effectively. The “Not Invented Here” (NIH) syndrome can create barriers, leading to the dismissal of valuable external ideas. Employee competencies are critical, and misalignment with team members can result in failures. At the meso level, an organizational culture that discourages risk-taking and does not tolerate failure can stall the open innovation process. When open innovation projects lack connection and consistency with the company’s business model, underperformance and failure can occur. Risks related to asset complementarity, chain characteristics, and persistent NIH at the inter-organizational level, along with ineffective knowledge transfer, pose significant challenges. As with Pathway 1, the macro level presents no failure mechanisms to analyze in this context.

3.1.3 Pathway 3: managing knowledge inflows/outflows

This pathway leads to the dynamic processes of knowledge inflows and outflows within the context of open innovation. Central elements in this pathway include knowledge assimilation representing the internalization and integration of external knowledge within an organization, and aligning it with existing capabilities and objectives to create value. The other core sub-theme within this pathway is the role of absorptive capacity as the organization’s ability to effectively identify, acquire, and apply external knowledge, emphasizing its capacity to absorb, adapt, and leverage this knowledge for innovation and competitiveness. The pathway through many empirical examples underscores that external knowledge, while valuable, may not seamlessly align with an organization’s existing capabilities unless it is harmonized with their specific business needs and grafted onto their existing operations.

Failures in managing knowledge flows:

At the micro level, cognitive abilities and role identities can impede the effective assimilation of external knowledge within organizations. Failures can also arise from issues related to bisociative cognition and the quality of external knowledge. External knowledge that is incompatible with an individual’s existing capabilities can result in suboptimal outcomes. At the meso level, failures may stem from the inability to recognize and locate cross-border knowledge, both in terms of the search for relevant knowledge and its integration. Furthermore, the lack of organizational ambidexterity, which involves balancing the exploration and exploitation of knowledge, can hinder the effective assimilation of external knowledge. At the macro level, failure can result from an organization’s inability to reconfigure its knowledge in response to external market movements. Additionally, the knowledge climate, both locally and at a distance, can affect the efficacy of knowledge flows and their alignment with the organization’s strategic objectives.

3.1.4 Pathway 4: the fuzzy front-end of the innovation process

This pathway leads to the multifaceted process of developing new products and services. It deals with the “fuzzy front end,” the initial stage of innovation where ideas are generated and preliminary concepts take shape. The subsequent research and development (R&D) stage is a critical phase where ideas are refined and developed into tangible offerings. The research along this pathway deals with the concept of “outside in” and emphasizes the importance of considering external perspectives, such as customer feedback and market insights, in the innovation process. Moreover, it highlights the active engagement of consumers in new product development (NPD) and new service development (NSD), illustrating the growing trend of co-creation and collaboration in shaping new offerings.

Failures in the fuzzy front end of innovation:

At the micro level, limited attentional capacity can make the management of multiple issues less effective when these issues compete for the attention of top management teams during the NPD and NSD processes. This may result in crucial aspects being overlooked or underemphasized. At the meso level, failures can arise from the absence of robust legal strategies to protect intellectual property, as well as inadequate technological resources within the organization. Such failures can harm the development of innovative products and services. At the macro level, industry-level factors, such as the pace of technological change (industry-level clock), the lack of technological diversity or intensity in the market, and a scarcity of competition, along with environmental contingencies, can collectively influence the success or failure of NPD and NSD initiatives.

3.1.5 Pathway 5: the quadruple helix

Research on this pathway deals with the dynamics of collaboration between small and medium-sized enterprises (SMEs), university-industry collaboration and public partnerships. It examines the role played by entrepreneurial agents within the quadruple helix model. On this pathway the interactions among academia, industry, government, and civil society are examined as open innovation modes. Open innovation at the project level receives attention, providing a more granular perspective on collaborative network efforts and showing how individual and organizational levels interact.

Failures in the quadruple helix:

At the micro level, issues related to team openness, interpersonal skills, and leadership have been found to be critical factors for university–industry collaboration and innovation. At the project level, ambiguities surrounding project goals among partners can lead to misalignment and underperformance. Meso-level challenges encompass measurement issues and key performance indicator (KPI)-related challenges, including the need for interoperable KPIs and the potential influence of bureaucratic hurdles in different institutions. At the macro level, dilemmas related to proximity, market conditions, and governmental support can influence the success or failure of collaborations between SMEs, universities, industries, and government entities, affecting the larger innovation landscape.

3.1.6 Pathway 6: OI and resilience

This pathway leads to exploring the intricate relationship between open innovation and the concept of ecosystems. It emphasizes the interplay between resilience and the ecosystem’s health in the context of innovation. The research on this pathway deals with subjects related to exogenous shocks. An example is the impact of events like the COVID-19 pandemic on open innovation practices. Grand challenges are a focal point of this pathway, leading to discourse about how open innovation can address and contribute to overcoming societal issues. Additionally, the transformation of business models in the context of societal challenges is a key feature. Analyzing such transformations shows how open innovation can catalyze the evolution of organizational strategies and structures.

Failures in OI resilience:

At the meso level, business model failure is risky, particularly when organizations do not change their traditional business models to align with new market dynamics and innovation logic. Inconsistencies in vision regarding innovation can create challenges in navigating open innovation successfully. Resistance to change, particularly in traditional non-digital business models, and a lack of organizational agility, can stall innovation efforts. At the macro level, market turbulence is identified as a potential failure factor. The unpredictable nature of markets, particularly in the face of exogenous shocks, can pose significant challenges to open innovation initiatives. This can potentially lead to ecosystem failure. On this pathway, micro-level failure mechanisms are as yet unexplored.

3.1.7 Pathway 7: appropriation strategies

This pathway leads to intellectual property management in open innovation. It mainly deals with phenomena related to external technology acquisition. Licensing is fundamental to this pathway, as it enables organizations to grant or obtain rights to use, develop, or commercialize specific technologies. The value of licensed patents is a key discussion point, showing the value of patents as assets in open innovation. This pathway notably emphasizes the significance of technology-related strategies in open innovation practices.

Failures in appropriation strategies:

At the micro level, failure can come from a lack of meaningful interaction between individual licensees and licensors. This can impede the effective exchange of knowledge and technology. Reverse learning, where knowledge flows in an undesired direction, can also pose challenges. At the meso level, failures may stem from ineffective intellectual property (IP) strategies, as well as a lack of market knowledge, which can affect the organization’s ability to protect and leverage its technology effectively. At the macro level, the absence of market-level technology information, which involves actively seeking external technologies on a broader scale, can be a failure factor, potentially resulting in missed opportunities.

Additionally, the paradox of depth of openness and closeness in appropriation strategies is partially discussed on this pathway. The imbalance found to lead to issues such as anti-commons (resource underuse), trolling (unfair patent assertion), and the multiplication of wasteful litigations. These issues can all weaken the effective use of intellectual property in open innovation initiatives.

3.1.8 Pathway 8: platforms and communities

This pathway is characterized by a rich body of literature focused on consumer engagement as an OI mechanism. It encompasses the microfoundational aspects of engagement, including cognition and behavior, to unravel how consumers participate in various innovation communities. Usercommunities, within which tangible incentives, formal authority, and established institutions are notably absent, are central to this discourse. The pathway encompasses innovations ranging from user-led changes to open platforms. It showcases the diverse ways in which consumers contribute to innovation.

Failures in platform and communities:

At the micro level, the motivation for participation is pivotal. Failure can arise when consumers lack incentives or enthusiasm to engage actively. The diversity and effectiveness of consumers’ creativity portfolios, as well as the leadership within informal institutions, can significantly affect the outcomes of consumer engagement efforts. At the meso level, challenges can stem from a lack of ways to measure user contributions to innovative products, and thus failing to reward them effectively. At the macro level, failures may result from difficulties in adopting engagement strategies in line with socio-cultural factors and gaining collective approval. Governance failures, which pertain to the structures and processes governing consumer engagement, can weaken the effectiveness of user communities in shaping innovations. The notion of “empty bar symptoms” represents unique and noteworthy failure factors in this context. It may signify challenges related to participation, productivity, or the fulfillment of expectations within consumer engagement scenarios.

3.1.9 Pathway 9: OI activities, firm performance, and output

This pathway primarily leads to understanding how access to external technologies can affect both modular and radical forms of innovation, and ultimately a firm’s innovation performance. The Quadruple Helix model also appears here, showing the roles of customers, suppliers, and universities in shaping innovation outcomes. Notably, positive innovation output is observed when these stakeholders are involved, but cross-sector collaborative innovation may negatively affect innovation output. Additionally, the pathway explores the effects of inbound and outbound activities on innovation performance. Research on this pathway shows that inbound activities improve radical innovation performance, but impede incremental innovation performance, while focusing on outbound activities produces the opposite effects.

Failures in OI activities and performance:

Failure mechanisms in this pathway are not detailed at the micro level. At the meso level, challenges can arise from issues related to organizational capability and routines, the firm’s ability to consistently access and evaluate external knowledge resources, the lack of organizational ambidexterity, the excessive practice of open innovation, and the firm’s technological capabilities impeding organizational ability to carry out OI practices.

At the macro level, failure can result from slow changes in the technological environment, particularly in mature industries where innovation may be slower to evolve or adapt to external factors.

3.1.10 Pathway 10: crowdsourcing

This pathway leads to understanding the process of idea generation and how innovation contests facilitate it. At the microfoundational level, the focus is on motivation theory, examining what drives individuals’ participation in these contests. Social exchange theory is a central framework used in this pathway for understanding sociological and psychological factors related to the dynamic interaction between two parties. Notably, research is limited on how organizations and systems affect these processes. Most studies focus on individual and small-group dynamics.

Failures in crowdsourcing:

At the micro level, failures can occur when individuals participating in contests underinvest their efforts, leading to suboptimal solutions. Misalignment between the motivations of solvers and seekers (those seeking solutions) can hinder the success of idea generation. The lack of perspective on the ultimate impact of their solutions may also result in failures, because solvers may not fully comprehend the potential value of their contributions. Additionally, a lack of monetary reward and trust in contest platforms can act as deterrents. At the meso level, failures may stem from organizations ineffectively implementing the suggestions generated in contests. The organization’s ability to recombine knowledge, its absorptive capacity, and its ability to proactively provide and receive suggestions can affect the success of idea generation and innovation contests. Specific failure mechanisms are not detailed for the macro level in this context.

Table 4 summarizes the results of the open innovation pathways, main features, and failures.

3.2 Results of Mann–Kendall test

As previously noted, we employed the weight of each topic per year to analyze the annual shifts in open innovation research. Figure 5 visually captures the evolution of these topics from 2003 to 2023. At a glance, it appears that the publication proportion for all topics experienced fluctuations, especially between 2003 and 2005. For a more rigorous understanding of these observed trends, we applied the Mann–Kendall test. The results of this test, delineated in Table 5 , give a statistically substantiated account of the topic trajectories.

Temporal trends in open innovation research topics (1993–2023)

The Mann–Kendall Test results presented in Table 5 provide valuable insights into the annual trends of open innovation research topics over a specific time period. Each research topic has been examined for its trajectory, with particular attention paid to the direction and significance of trends, denoted by p -values and z-scores. Moreover, the tau statistic has been employed to gauge the strength and direction of these trends, offering a comprehensive perspective on the evolution of each research theme.

In our analysis, we observed that some topics have experienced a noteworthy decline in research interest. Notably, “Value Creation and Capture Process” (Topic 1) and “OI Strategic Management” (Topic 2) exhibit decreasing trends with p -values of 0.009 and < 0.000 respectively, accompanied by negative z-scores of − 2.605 and − 3.984. These findings suggest that scholarly attention to these topics has waned over the studied period.

On the other hand, certain research areas have seen a surge in interest. “Quadruple Helix” (Topic 5) and “OI and Resilience” (Topic 6) display increasing trends, with highly significant p -values of 0.034 and 0.001, and positive z-scores of 2.116 and 3.177 respectively. These results signify a growing focus on collaborative endeavors, business models, and ecosystem dynamics within the academic community. Meanwhile, “Managing Knowledge Inflows and Outflows” (Topic 3), “The Fuzzy Front-End of Innovation” (Topic 4), “Platforms and Communities” (Topic 8), and “Crowdsourcing” (Topic 10) present no significant trends, as indicated by their p -values and z-scores. These research themes have maintained a relatively stable level of attention in recent years. Finally, “OI Outputs” (Topic 9) has emerged as an area of increasing significance, shown by a significant p -value and a positive z-score of 5.324. This points to a notable uptick in scholarly focus on factors affecting firm performance within the open innovation context.

The inter-topic distance map provides valuable insights into the relationships and proximities between the identified topics in our open innovation research (Fig. 6 ). The two-dimensional visualization provides an insightful representation of the relationships between the topics in our corpus. The x and y axes represent the Inter-topic Distance Map, where each bubble represents a topic, and the distance between the bubbles indicates how distinct or similar the topics are from each other.

Inter-topic distance map

The map shows that Topic 10 (Crowdsourcing), Topic 5 (Quadruple Helix), and Topic 8 (Platforms and Communities) are very similar. This is likely because crowdsourcing is often enabled by platforms and communities. Topic 1 (Value Creation and Capture Process) and Topic 2 (OI Strategic Management) are also close together on the map, because the two topics are closely related. Open innovation is a process that companies use to create new value and develop new services by leveraging external resources and ideas.

“The Fuzzy Front-End of Innovation” (Topic 4) and “OI Outputs” (Topic 9) exhibit intertwined themes. The cross-linkage of terms such as firm , product , and strategy reflects the potential interplay between product development and the overarching performance of the firm. It signifies that the effectiveness of new products or service developments often translates to the overall performance metrics of firms.

However, what stands out is “Managing Knowledge Inflows and Outflows” (Topic 3). Accompanied by terms like knowledge , absorptive capacity , and transfer , this topic encompasses the mechanics of managing, assimilating, and exploiting knowledge from both internal and external sources. Topic 3 indicates that knowledge management is a broad theme that may intersect with other OI topics without being tied to particular settings. Additionally, the intertopic map reveals three distinct controversies in the open innovation scholarly research community, which we will discuss and use as guidelines for future research directions.

4 Discussion in the current landscape of OI research: pathways for future research

Intertopic distance maps serve as strategic guides in topic modeling to uncover potential research directions in the OI research field. The gaps or distances between topics on such maps can show valuable insights. They may indicate under-researched areas for future research, or point out theoretical divides that call for new or integrative theoretical frameworks. They also show visually how mature or saturated certain research areas are based on topic clustering. Additionally, the spatial separation between topics can show the need for interdisciplinary research to bridge related domains. By focusing on these distances and the relational dynamics they represent, we identify and prioritize three areas where further investigation could yield significant contributions to OI fields and topics. Then, we discuss our analytical results regarding failure in the field of open innovation. Our discussion section also informs avenues for future research.

4.1 The OI landscape

4.1.1 controversy 1: the distance between managing knowledge flows and the oi main topic cluster.

One could assume that managing knowledge flows constitutes the core of all open innovation (OI) activities and processes. The large gap between this topic and other principal OI topics has scholarly significance, requiring further understanding. We point out several reasons for this observation, looking in depth at the following topics: The literature comprising Topic 3 employs specialized terminologies tied to the knowledge management and knowledge economy sectors, mainly through the lens of the knowledge-based view (KBV) of the firm (e.g. Brunswicker and Vanhaverbeke 2015 ; Santoro et al. 2018 ; Chiang and Hung 2010 ). Conversely, the core cluster of the open innovation (OI) field is characterized by a prevalent adoption of the resource-based view (RBV) as the theoretical underpinning (e.g. Chesbrough and Crowther 2006 ; Mortara andMinshall 2011 ; Du et al. 2014 ). Thereby, it highlights a divergence in theoretical perspectives within OI research. A potential angle for future research in open innovation is to promote research using theoretical pluralism and cross-disciplinary projects. Few researchers have proposed ways to implement theoretical pluralism and combine lenses in management research. Okhuysen and Bonardi ( 2011 ) explain that the challenge in developing “multi-lens” theories lies in the conceptual closeness of the theories being integrated and the extent to which their foundational assumptions align. Their solution is a so-called “paradigm sliding.” This entails combining theoretical perspectives that are conceptually close and harmonious in terms of their fundamental premises. In general, the distance between the topics could be shortened by promoting multi-lens contributions.

4.1.2 Controversy 2: The distance between OI output and the OI main topic cluster

The open innovation concept and its research rest on the notion that collaboration positively influences innovation (Audretsch and Belitski 2024 ). Despite theoretical recognition of the crucial role external knowledge plays in enhancing a firm’s innovation and productivity through knowledge transfer or spillovers (Dahlander and Gann 2010 ; Bogers et al. 2018 ), empirical studies on OI outcomes are scarce. The complexity of such empirical research (Audretsch and Belitski 2024 ; Mention 2011 ) may contribute to the data sparsity on OI output, which, in turn, accounts for the observed research gap. Nonetheless, our findings suggest that this topic is burgeoning, so it presents an exciting avenue for future inquiry. Future research on OI could benefit from the development of new, robust structural indicators that offer a clearer measurement of OI outcomes.

4.1.3 Controversy 3: the distance between appropriation strategy and the OI main topic cluster

In the literature of strategic management and initial studies of open innovation (OI), the discussion often focused on appropriation strategies as a key means to implement OI activities, especially how firms safeguard and leverage their intellectual property, licensing, and competitive advantage. As the OI field has evolved, research has expanded to encompass the broader integration of external and internal ideas to drive innovation. This shift has led to the emergence of distinct research communities and diverse methodological approaches . The appropriation strategies topic, which typically involves technological innovation, technology procurement, and patent analysis (e.g. Guo et al. 2016 ; Noh and Li 2020 ; Klechtermans et al. 2022 ), illustrates one of the challenges in drawing the OI field’s boundaries. This subject area is often explored through econometric methods and the analysis of patent data and large technological innovation datasets. Conversely, contemporary OI research primarily examines the “how”—the practices of the OI process—with limited attention to technological valorization and IP management. This diverges from Chesbrough’s initial focus when introducing the OI concept (Chesbrough 2003a , b ). Researchers with an interest in the topic of open innovation could make a significant contribution by bridging these two research communities, renewing the focus on appropriation strategies.

4.2 OI pathways through the lens of failure

Our abductive analysis shows researchers have examined OI failure at the micro-level. Specifically, learning and culture were found to contribute to risk in the majority of topics. This aligns with Cricelli et al. ( 2023 ), who discussed elements of OI adoption resistance, “not invented here syndrome” (NIH), and similar micro-foundational issues. Our contribution to the micro-foundational elements includes the cognitive limitations of individuals and the limited attentional capacity of top management teams in managing and organizing for open innovation.

When discussing cognitive limitations, we refer to the inability of individuals to assimilate knowledge within organizations. This perspective goes beyond prior studies, which assume the success of collaboration relies on the interpretation and perception of members about themselves and others in the collaboration (e.g., Skippari et al. 2017 ). Another micro-level factor that could better inform the future of OI research is the attentional capacity of management teams toward OI activities within organizations. In a study by Sisodiya et al. ( 2013 ), it was found that managers gave different levels of attention to inbound versus outbound OI activities and their potential effects. This imbalance negatively affected OI outcomes. When examining micro-level risk factors for organizing OI activities, organizational behavior theories such as selective attention theory could enrich research on OI failure.

At the meso level, significant risks associated with OI failure include inadequate business model adjustments (e.g., Albats et al. 2023 ), IP-related failures (e.g., Grandstrand and Holgersson 2014 ), and challenges related to measuring OI performance at the organizational level (e.g., Brunswicker and Chesbrough 2018 ). Research on OI failure at the organizational level is the most developed, which is not surprising given that OI is mainly developed and practiced at this level. However, some factors remain relatively new to the field and call for further investigation.

One such factor is the excessive practice of OI, which refers to situations where an organization overinvests in building external relationships, ideas, methods, and innovations without considering the specific requirements of each investment (e.g., Greco et al. 2016 ). Research on OI failure at the meso level could benefit from exploring the question of what constitutes efficient and balanced OI activities.

At the macro level, our findings align with those of Bertello et al. ( 2024 ), indicating that this is the least developed research domain in both OI research and in addressing failure. The impact of external influences on OI has been discussed previously, particularly in the context of post-COVID-19 scenarios, where OI was used as a strategy for business continuity during crises (e.g., Liu et al. 2022 ; Bertello et al. 2022 ). These studies demonstrate that overcoming crises often necessitates open innovation practices, especially for SMEs, to mitigate the negative impacts of a large-scale crisis such as the pandemic (Markovic et al. 2021 ).

However, research has overlooked the influence of economic crises on ongoing OI activities of firms. Two research foci that we found particularly interesting and underexplored are the effects of stagnant economic growth and market turbulence on open innovation activities. It remains to be seen how a stagnant market or industry impacts the OI activities of companies and whether marginal economic growth in a sector challenges collaborative innovation. Similarly, research on OI has not sufficiently addressed the challenges posed by market turbulence, such as high variations in customer preferences and product demand (Jaworski and Kohli 1993 ), on existing OI processes.

5 Conclusions

In the pursuit of open innovation, this research presents a multifaceted analysis of ten pivotal pathways researched in the past two decades in the OI domain, proposing insights into the micro, meso, and macro levels of failure mechanisms that can affect open innovation initiatives (see Table 4 ) in addition to presenting the current state and potential future directions of the field.

Based on our results and arguments, this study proposes a way forward in the OI research domain by uncovering its pathways in the past two decades and analyzing the multifaceted mechanism of failure in each pathway. In this research we have identified key trends, patterns, and shifts that have shaped the current landscape of open innovation. This kaleidoscopic analysis allows us to pinpoint specific pathways and anticipate risk factors. Furthermore, our study unpacks the complexities of failure mechanisms and the potential for future research along different OI pathways, shedding light on their micro, meso, and macro levels.

We emphasize the lack of research on macro-level mechanisms. This analytical insight suggests that while organizations concentrate on internal and inter-organizational factors, broader contextual aspects of open innovation, such as regulatory, economic, and market influences, remain relatively unexplored. Collaboration in various forms is the backbone of OI, whether it involves other firms, universities, government entities, or consumers. Challenges related to individual/employee networks and team dynamics, intertwined with the ambiguity of collaborative project goals, have impeded open innovation efforts. Organizations should actively promote open communication, trust-building, and role clarity in collaborative networks.

Finally, the analysis of the pathway on “OI and Resilience” shows the importance of the business model as an adaptable artifact in the face of external shocks and societal challenges. Business models could act as artifacts connecting organizations to their environment and to other actors, thus embracing a panoramic view of the organization’s OI strategies.

For scholars, the pathways we have found offer a valuable roadmap for future research, guiding them to analyze the nuances of open innovation failure. Our findings emphasize the importance of considering not only individual and organizational factors, but also the broader system and the context of OI to understand how these initiatives can thrive or fail. Our analysis also leads to recommendations for organizations seeking to implement open innovation. First, by identifying and understanding the specific failure mechanisms at the micro, meso, and macro levels, organizations can develop interventions targeted at these risks. For instance, depending on the OI pathway, a firm can address cognitive limitations and attentional capacity at the micro level to improve individual and team performance in OI initiatives. At the meso level, organizations can refine their business models and IP management practices to better align with OI objectives and ensure more robust and resilient innovation processes. Furthermore, by considering the macro-level influences such as economic conditions and market turbulence, firms can adapt their OI strategies to be more responsive to external shocks and uncertainties. Ultimately, insights from our research can guide organizations in fostering more effective collaborations, optimizing resource allocation, and achieving innovation outcomes in a dynamic and complex business environment.

Finally, while we intend to show the OI pathways and the mechanisms of failure within them, our research is not without its limitations. One such limitation is the inherent dependency of our findings on the accuracy and efficiency of topic modeling algorithms. Topic modeling is a powerful tool for identifying themes and patterns within large datasets. However, the quality of its results depends on the selection of parameters, preprocessing steps, and the algorithm used (Hannigan et al. 2019 ). Furthermore, topic modeling does not account for the contextual nuances and subtleties of the text. This could result in overlooking important details and insights. The second limitation is due to the abductive analysis of the texts. While valuable for generating insights from the data, it is inherently subjective and influenced by the researchers’ perspectives and experiences. This subjectivity can introduce biases and affect the interpretation of results. The iterative nature of abductive analysis relies on the researchers’ ability to identify and make sense of patterns. This aptitude can vary significantly between individuals (Tavory and Timmermans 2014 ). Additionally, the interpretive layer added to the analytics can lead to different conclusions depending on the researchers’ backgrounds and prior knowledge. For future research, scholars in the OI field could advance their algorithms and combine multiple methods to validate the robustness of their findings. In addition, future researchers could use mixed-method approaches to reduce the risks of oversimplification in interpretative analysis.

Data availability

The data for this study has been derived from Web of Science database.

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Mahdad, M., Roshani, S. The open innovation kaleidoscope: navigating pathways and overcoming failures. Rev Manag Sci (2024). https://doi.org/10.1007/s11846-024-00804-7

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Research on the flipped classroom + learning community approach and its effectiveness evaluation—taking college german teaching as a case study, 1. introduction, 2. literature review.

How can a learning community be constructed within a flipped classroom?
What is the impact of the flipped classroom combined with a learning community model on learners’ academic performance, compared to the flipped classroom model alone?
How does the flipped classroom combined with a learning community model influence learners’ perceptions, compared to the flipped classroom model alone?

3. The Construction of Flipped Classroom + Learning Community Model

The Seamless Merger of Personalized and Collaborative Learning Environments. The model conceptualizes the autonomous learning milieu in flipped classrooms and the collaborative learning setting within learning communities as analogous to the complementary polarities in Tai Chi, where they maintain their autonomy while interweaving seamlessly. Embedded within the personalized learning milieu, there exists the potential for collaboration through discussions, negotiations, and reciprocal learning frameworks within communities, accelerating learners’ cognitive progression. After independently engaging with learning materials, such as watching micro-lectures or completing tasks, learners can immediately share their insights and receive feedback from their community, significantly enhancing knowledge retention. Additionally, these knowledge-focused discussions contribute to the vitality of learning communities by providing a continuous flow of topics, fostering camaraderie among members, and gradually shaping a strong sense of collective identity and cohesion. In the collaborative setting of a learning community, individual development is not only tolerated but actively promoted, where differences in interests and strengths are embraced as strengths. This heterogeneity among members fosters a unique dynamic where each member can observe and learn from others, leading to the expansion of individual knowledge and competencies. Notably, personalized learning environments within this community can manifest in overt or covert ways. In overt instances, such as collaborative task completion, experienced learners on a given topic may assume leadership roles, sharing their expertise and guiding the evolution of the community’s collective knowledge. Meanwhile, other members engage in personalized learning through targeted questions, consultations, and feedback sessions. Conversely, implicit personalized learning occurs through subtle mechanisms of observation and imitation. For example, a learner facing challenges in vocabulary acquisition might unconsciously improve by observing and adopting strategies from proficient peers. Similarly, learners deficient in social skills or time management can also benefit from this covert form of learning. In essence, while personalized and collaborative learning environments exhibit distinct characteristics, they are not mutually exclusive entities defined by discrete learning phases or physical spaces (e.g., in-class versus out-of-class settings).
The pivotal goal revolves around the constructive evolution of both individual and collective knowledge frameworks. This teaching model meticulously blends personalized learning milieus with collaborative learning ecosystems within the learning community, geared towards nurturing and accelerating the construction of both individual learners’ knowledge and the collective knowledge of the group, akin to the converging gray area depicted in the Tai Chi diagram. It underscores that neither personalized nor collaborative learning environments can be neglected in achieving the goal of knowledge construction, as their synergy is vital. Moreover, the model incorporates the process of knowledge construction within the framework of Bloom’s Taxonomy of Cognitive Domains, illustrating that this process does not adhere to a rigid linear progression, nor do the cognitive levels in Bloom’s Taxonomy necessarily escalate sequentially. Instead, knowledge construction progresses in a spiral manner, with potential intersections or skipping across cognitive objectives. The confinement of knowledge construction to static learning environments is a misconception. While it is commonly assumed that memorization and comprehension primarily occur in individual settings, this notion is challenged by the fact that these processes can also be facilitated through collective endeavors within learning communities, such as shared recitation and mutual clarification. Furthermore, the belief that analysis, application, reflection, and innovation are inherently collaborative undertakings is also contested, as these cognitive objectives can equally be cultivated within personalized learning environments, demonstrating the versatility and interconnectedness of different learning modalities. It is essential to emphasize that individual and collective knowledge are not independent constructs or aspirations, but rather complementary aspects of the learning ecosystem. The collective knowledge within a learning community arises from the harmonious blend of individual efforts, as members collaborate, share insights, and engage in deep analysis to reach shared comprehension and develop a distinctive learning culture. This process is fundamentally driven by the social negotiation and construction of individual knowledge, where each individual’s cognitive landscape is enriched by the collective, and vice versa. The intertwined dynamic between individual and collective knowledge within a learning community fosters a continuous upward spiral, nurtured by both personalized and collaborative learning modalities. Consequently, the design of educational content, instructional methodologies, and assessment frameworks must encompass the dual imperatives of advancing both individual and collective knowledge development.
The holistic learning environment is fortified by a diverse array of resources, seamlessly integrated and ubiquitous in their support of learning objectives. The proliferation of information-enabled educational technologies has significantly enriched the learning resource landscape. This encompasses a comprehensive spectrum, including flipped classroom resources, online resources, social resources, and the shared repertoire within a learning community, all of which are designed to cater to the varying demands of constructivist learning across multiple scenarios. Flipped and online resources range from curated micro-lectures and accompanying instructional materials to a panoply of digital assets, such as visuals, audios, videos, written content, websites, and innovative tools for interaction, documentation, and content creation (e.g., instant messaging platforms, massive open online courses, blogs, vlogs, and open-source platforms fostering user-generated knowledge). Social resources are multifaceted, encompassing teachers, renowned experts and scholars in specific domains, and individuals who reside within learners’ immediate learning ecosystems, offering invaluable assistance. The learning community’s shared skill repository represents a rich tapestry woven from the diverse talents and contributions of its members, intertwined with the collective intelligence embodied in their collaborative endeavors. This includes tangible outputs like project accomplishments and discussion archives, as well as intangible elements like the community’s discourse norms, learning ethos, and sense of belonging. This collective knowledge, which is both a product and a catalyst of community development, stands as a vital resource underpinning its continued growth. Additionally, there are intersections between these resource categories, with flipped resources, for instance, often incorporating online resources like MOOC videos, articles, and various digital platforms and tools. The endorsement from experts in certain disciplines, as part of social resources, often manifests as learners’ ability to procure pertinent resources via online platforms. Consequently, the categorization of resource types outlined in this roadmap aims to form an exhaustive list, embracing all potential avenues that can bolster learners’ knowledge construction endeavors. This underscores the model’s inclusivity and adaptability towards various resource types. Notably, these resources are not confined to a singular learning phase or environment, transcending the boundaries of both in-class and out-of-class contexts. Instead, they are seamlessly integrated across both personalized and collaborative learning ecologies, aligned with the model’s core mission to support constructive learning that transcends the traditional classroom paradigm.
Repositioning the Teacher’s Role. This model eschews rigid definitions of teacher and student roles, mirroring the spontaneous nature of teaching and learning in a constructivist environment where the where, how, and by whom these activities occur are not predetermined. The flipped classroom model reverses the traditional script, pushing knowledge transmission and explanation beyond the confines of the classroom, encouraging teachers to descend from their authoritative perches and morph into instructional designers and supporters, intimately involved in identifying and supporting struggling students. In a learning community, membership and roles evolve organically in response to the learning themes, fostering an environment of equity and mutual respect. Core roles are not externally imposed but emerge naturally within the community’s fabric; for instance, when a learning theme aligns with a member’s domain expertise, they naturally ascend to the role of an expert, while others, through observation and participation, gradually attain core status. This cycle repeats as the community tackles new learning themes. Within the flipped classroom + learning community approach, teachers’ roles are not monolithic, but rather fluid, shifting within each community context. The teaching–learning dynamic extends beyond the classroom walls and lecture-style interactions; learners can accumulate knowledge through observing their peers within the community or engaging directly in practical experiences. In this framework, which aligns with contemporary educational structures, teachers retain a pivotal organizing role, particularly at the onset, by providing robust infrastructure for personalized and collaborative learning environments. This encompasses resource curation, community facilitation, guidance, and assistance with overcoming practical obstacles. Additionally, teachers serve as invaluable social resources and domain experts, offering learners accessible knowledge support that is constructive rather than prescriptive. They can also engage as active members within the learning community, forming the cornerstone of a collaborative teacher–student community. Although this study primarily explores the construction of student peer learning communities, the model’s applicability extends to fostering teacher–student learning communities as well.
Positioning in-class and out-of-class activities as contextual backdrops. The flipped classroom paradigm harmoniously fuses traditional and digital learning modalities, enhancing educational outcomes. Nevertheless, the foundational model’s clear delineation of these phases, while emphasizing the novelty of the “flipped” approach, fails to capture the intricate, spiral dynamics of learning construction and cognitive elaboration central to constructivist perspectives. This segmentation may inadvertently foster disjointed learning experiences due to insufficiently nurtured learning environments and inadequate resource provisioning. The inflexible dichotomy between extracurricular and in-class learning, as embodied in the traditional flipped classroom model, poses a significant challenge for courses already burdened with inadequate class hours. By allocating extracurricular time primarily for self-study through video lectures, aiming at foundational knowledge acquisition, and reserving in-class sessions for collaborative endeavors that should ideally encompass application, analysis, reflection, and innovation, students may find their extracurricular tasks insufficiently enriching, fostering a limited understanding. Moreover, the condensed in-class period may prove inadequate for the thorough exploration of higher-order cognitive objectives, while the ad hoc collaborative environment may not adequately support effective collaboration. This formalistic adherence to the flipped classroom framework, neglecting the need for adaptability, has emerged as a critical obstacle hindering its further advancement. With the advancement of educational theories and practices, the cornerstone of the constructivist-oriented teaching model shifts from the mere dissemination of knowledge to the cultivation of an environment that nurtures learners’ knowledge construction. Learning is a perpetual, boundless endeavor that transcends temporal and spatial constraints, mirroring the essence of constructivist learning and the learning culture embraced in the digital age. Hence, the conventional dichotomy between in-class and extracurricular segments in the flipped classroom paradigm fades into the background, transforming into a contextual framework. In-class interactions embody the synchronous engagement of teachers and learners, empowering teachers, as experts, to efficiently observe and guide learning communities and individuals during direct encounters. Additionally, the mutual observation among learning communities sparks introspection and deliberation within each collective, emphasizing that in-class and extracurricular experiences, akin to learning resources, intertwine and permeate the entire learning ecology.

4. The Effectiveness of Flipped Classroom + Learning Community Model

4.1. participants, 4.2. instruments and procedure, 4.3. data analysis, 4.4. the results, 4.4.1. academic performance, 4.4.2. learner perception development.

During the first semester, I found the flipped classroom quite novel because I could arrange my own time. Also, since it’s a brand new language, being able to listen and watch repeatedly is of great help to my learning. I wouldn’t worry about not understanding in class and how to make up for it after class. If I didn’t understand something, I could always go back and review it. I felt this was extremely beneficial for laying a solid foundation. In general, I have a relatively high acceptance of the flipped classroom model.

G4S2: The main difficulty I faced during the first semester was with the classroom activities. Since everyone was still unfamiliar with each other, but we were expected to interact frequently, it felt quite awkward.

G3S4: Although this method can enhance learning, I often find it challenging to fully prepare for class because I rely heavily on self-study. Unfortunately, I’m not particularly disciplined, so there are times when I don’t do as much advance preparation as I should. Consequently, during class, I sometimes struggle to fully understand the material.

With the encouragement and oversight from the learning community in the second semester, I was able to better adapt to the flipped classroom model, and both my study time and efficiency have improved. I think the flipped classroom is working quite well now.

Especially when it comes to grammatical points, it’s incredibly helpful. It also significantly aids in vocabulary acquisition and enhances my listening, speaking, reading, and writing skills. Initially, when I started memorizing German vocabulary, I had a hard time remembering the gender of words—masculine, feminine, and neuter. I would often mix them up. However, I mentioned this issue in our learning community, and Zhang (G2S2) suggested associating and grouping the words together. I adopted her method, and it really helped me retain the information more firmly. Regarding listening, speaking, reading, and writing, we regularly practice these skills after each unit. For instance, we’ll dictate or write down the words after completing a unit. Additionally, during our discussions, we often read out loud from the texts, and my peers kindly correct my pronunciation whenever I mispronounce something. I find these practices incredibly useful.

I believe that language courses are generally quite suitable for FC + LC model. Since we’re learning a foreign language, and normally in school, we only speak Chinese, there’s a lack of language environment, especially when it comes to learning German. Therefore, I think the learning community model is quite fitting for language courses. I hope to continue using the flipped classroom combined with the learning community model in the next semester, and I’m willing to continue forming a community with the other two community members.

5. Discussions

6. limitations and future research.

Experimentation and iterative refinement of the FC + LC teaching model across a spectrum of disciplines, academic levels, majors, and cultural milieus, fostering a more nuanced comprehension of its practical implications.
Strengthening the empirical foundation by augmenting sample sizes and introducing control groups, thereby offering a more compelling argument for the superiority of the FC + LC model over the FC model.
Delving deeper into the mechanisms that govern learning community effectiveness in flipped classrooms, recognizing its direct bearing on learners’ academic achievement and perception development, with a view to mitigating the potential for the Matthew effect by elucidating the influencing factors and dynamic evolution of such communities, ultimately fostering sustainable learning outcomes within the FC + LC model.

7. Conclusions

Institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

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Click here to enlarge figure

VN.	N.	Max.	Min.	Mean	SD	Med.	Var.	P25	P75
FC	26	88.92	55.71	75.91	8.95	77.76	80.18	68.97	81.58
FC + LC	26	95.50	54.60	81.09	11.30	82.75	127.57	74.93	90.50

VN.	P2.5	P5	P10	P25	P27	P33	P50	P67	P73	P75	P90	P95	P97.5
FC	55.71	57.23	61.50	68.97	69.43	74.30	77.76	80.23	81.07	81.58	87.97	88.89	88.92
FC + LC	54.60	56.32	60.41	74.93	76.11	78.42	82.75	88.44	90.23	90.50	92.76	95.08	95.50

PV	Mean ± SD			t	df	p	Cohen’s d
PV	PG1:FC	PG2:FC + LC	DBPV	t	df	p	Cohen’s d
FC/FC + LG	75.91 ± 8.95	81.09 ± 11.30	−5.18 ± −2.34	−3.69	25	0.001 ***	0.72

Community nr.	Member 1			Member 2			Member 3			Average Scores in FC	Average Scores in FC
Community nr.	FC	FC + LC	Difference (FC + LC/FC)	FC	FC + LC	Difference (FC + LC/FC)	FC	FC + LC	Difference (FC + LC/FC)
G1	82.78	89.8	7.02	69.01	73.2	4.19	82.71	88	5.29	78.17	83.67
G2	66.39	75.5	9.11	78.75	91	12.25	78.06	72.7	−5.36	74.4	79.73
G3	88.92	94.3	5.38	75.91	81.7	5.79	62.12	60.8	−1.32	75.65	78.93
G4	80.76	90.4	9.64	68.84	85.7	16.86	64.67	78.5	13.83	71.42	84.87
G5	87.6	91.6	4	76.87	90.8	13.93	88.84	95.5	6.66	84.44	92.63
G6	75.43	92.1	16.67	77.46	79.9	2.44	55.71	63.5	7.79	69.53	78.5
G7	80.05	88.3	8.25	74.68	82.4	7.72	81.2	82.6	1.40	78.64	84.43
G8	80.18	82.9	2.72	70.48	54.6	−15.88	60.06	59.85	−0.56	70.24	65.67
G9	87.39	85.4	−1.99	/	/	/	78.7	77.6	−1.10	83.05	81.50

VN.	N.	Max.	Min.	Mean	SD	Med.	CV	t-Test	p	Cohen’s d
FC	25	4.36	2.91	3.69	0.41	3.91	0.11	−1.33	0.195	0.27
FC + LG	25	4.89	2.83	3.86	0.53	3.83	0.14	−1.33	0.195	0.27

Community nr.	Member 1			Member 2			Member 3			Average Scores in FC	Average Scores in FC
Community nr.	FC	FC + LC	Difference (FC + LC/FC)	FC	FC + LC	Difference (FC + LC/FC)	FC	FC + LC	Difference (FC + LC/FC)
G1	4.09	4.89	0.8	3	4.06	1.06	4	4.56	0.56	3.7	4.5
G2	3.45	3.5	0.05	3.91	4.06	0.15	3.36	3.72	0.36	3.58	3.76
G3	3.91	4	0.09	3.27	3.5	0.23	3.91	3.78	−0.13	3.7	3.76
G4	3.91	4.67	0.76	/	/	/	4.09	4.17	0.08	4	4.42
G5	3.91	3.28	−0.63	4.36	4.67	0.3	3.36	3.83	0.47	3.88	3.93
G6	3.91	4	0.09	4.09	3.78	−0.31	3	4.06	1.06	3.67	3.94
G7	2.91	3.83	0.92	3.73	3.94	0.22	3.18	4.28	1.1	3.27	4.02
G8	4	2.83	−1.17	3.27	3.33	0.06	3.82	3.56	−0.26	3.7	3.24
G9	3.91	3.22	−0.69	/	/	/	3.91	2.89	−1.02	3.91	3.06

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Wang, J. Research on the Flipped Classroom + Learning Community Approach and Its Effectiveness Evaluation—Taking College German Teaching as a Case Study. Sustainability 2024 , 16 , 7719. https://doi.org/10.3390/su16177719

Wang J. Research on the Flipped Classroom + Learning Community Approach and Its Effectiveness Evaluation—Taking College German Teaching as a Case Study. Sustainability . 2024; 16(17):7719. https://doi.org/10.3390/su16177719

Wang, Jie. 2024. "Research on the Flipped Classroom + Learning Community Approach and Its Effectiveness Evaluation—Taking College German Teaching as a Case Study" Sustainability 16, no. 17: 7719. https://doi.org/10.3390/su16177719

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Effectiveness of multifaceted implementation strategies for the implementation of back and neck pain guidelines in health care: a systematic review

Introduction

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Study selection and data extraction

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Synthesis of results

Identification and selection of studies

Quality of included studies

Effect on professional behaviour

Treatment behaviour

Effect on patient outcomes

Effect on cost of care

Strengths and limitations of this study

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The Multifaceted Sensemaking Theory: A Systematic Literature Review and Content Analysis on Sensemaking

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Acute lung injury and post-cardiac arrest syndrome: a narrative review

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Introduction

Epidemiology

Pathophysiology

ARDS post-CA

Lung compliance post-CA

Pulmonary edema and mechanical chest compression

Assessment and diagnosis

Potential therapeutic strategies for PALI

Managing hypercapnia

Optimizing PEEP, plateau pressure, and driving pressure

Factors associated with mitochondrial pathophysiology

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