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Core outcome sets and systematic reviews

• Mike Clarke 1 &
• Paula R. Williamson 2  

Systematic Reviews volume  5 , Article number:  11 ( 2016 ) Cite this article

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Systematic reviews seek to bring together research evidence to answer the question for the review. The reviewers usually wish to compare, contrast and, if appropriate, combine the findings of the existing research studies. However, these intentions are often thwarted by inconsistencies in the outcomes that were measured and reported in the individual studies. This, in turn, makes it difficult for readers of the review to use it to make informed decisions and choices about health and social care. One solution is for trials in a particular topic area to measure and report a standardised set of outcomes, which would then be used in the review. Core outcome sets are a means of doing this, providing an agreed standardised collection of outcomes for measuring and reporting for a specific area of health. In this commentary, we argue for greater involvement of systematic reviewers in the development and implementation of core outcome sets. This might help with, for example, the selection of outcomes to include in the Summary of findings tables that provide users of the review with the key quantitative findings. Consideration of core outcome sets when reviewers register their topics with Cochrane Review Groups or in PROSPERO would also help reviewers to plan their reviews. A greater uptake of core outcome sets across research, including systematic reviews, would help towards the ultimate aim of improving health and well-being through improving health and social care.

Peer Review reports

Systematic reviews seek to bring together the evidence from research that already exists, to answer the question for the review. In many cases, the aim is to combine the findings of the research studies in a meta-analysis, thereby increasing statistical power and precision of the effect estimate and supporting the conduct of additional analysis, such as the investigation of the effects in different subgroups. Even if there is no desire to combine the results of the studies, reviewers might wish to compare and contrast the included studies, to explore the effects of clinical and methodological heterogeneity. However, these intentions are often thwarted by inconsistencies in the outcomes that were measured and reported in the individual studies. It might not be possible to compare, contrast or combine the results of the individual studies because those results are presented for different outcomes. This contributes to waste in research [ 1 ]. It means that many reviews which would otherwise be able to pool results and generate robust effect estimates are unable to do much more than summarise the findings of each of the eligible studies as a separate piece of information. This, in turn, makes it difficult for readers to use the review to make informed decisions and choices about health and social care.

One solution, which would also help with streamlining the systematic reviewing process [ 2 ], is for all trials in a particular topic area to measure and report a standardised set of outcomes and for these outcomes to be used in the review. This would not limit the ability of researchers to examine other outcomes that might be of particular interest for their research but would mean that every trial could contribute useful data to the analyses of the key outcomes. One means to achieve this is through the development of core outcome sets, and we present the case for greater involvement of the systematic review community in their development and implementation in this commentary. It builds on an earlier commentary, encouraging greater use of core outcome sets in trial registries [ 3 ].

Core outcome sets

Core outcome sets are an agreed standardised collection of outcomes that should be measured and reported for a specific area of health. These sets represent the minimum that should be measured and reported in all clinical trials of a specific condition and are also suitable for use in other types of research and clinical audit [ 4 ]. Although there are examples of core outcome sets going back more than 30 years [ 5 ], and some well-established ones such as Outcome Measures in Rheumatology (OMERACT) for rheumatoid arthritis [ 6 ], they are still relatively rare. A systematic review, with searches up to 2013, found just under 200 in the published literature, across a wide range of areas but with many notable gaps, including for common conditions such as diabetes [ 7 ]. In some areas of health and social care, researchers might have already reached a stage where all (or almost all) studies measure more or less the same set of outcomes, but a formal process of agreeing on a core outcome set might still help to cement this informal consensus. This could also reinforce the important point that the standardisation which is achieved with a core outcome set is not intended to stifle innovation [ 4 ]. The outcomes in the set should represent the minimum to be collected in all trials, and researchers should continue to measure and report additional outcomes of particular relevance to their topic. Likewise, systematic reviewers should continue to seek data on those outcomes of particular relevance to their review, above and beyond those in the core outcome set.

If core outcome sets are to contribute to improvements in health and social care, by helping patients and the public, practitioners and policy makers to make better decisions about interventions, they need to contain the outcomes that really matter to these stakeholders.

They need to be developed in a collaborative way, with appropriate representation from key stakeholders, including practitioners, patients and others users of health and social care services; as well as researchers, policy makers and those who fund services and research [ 3 ]. Systematic reviewers from the relevant area of health or social care should be among these stakeholders in the development of core outcome sets. They may be able to help in relation to the review of outcomes previously measured in studies in the particular area and bring to the consensus process the perspective of the researchers who might have struggled most with inconsistencies in outcomes in the existing literature. Their involvement may facilitate the incorporation of these views into the process and help to identify ways to overcome some of the problems encountered by reviewers when selecting outcomes for their reviews and by users when reading reviews. Furthermore, explicit engagement of systematic reviewers in the development of core outcome sets may encourage subsequent uptake of these sets by this group of researchers.

In order to facilitate the positive impact of core outcomes sets on health and social care, the COMET (Core Outcome Measures for Effectiveness Trials) Initiative ( www.comet-initiative.org ) is seeking to support others in the development and uptake of core outcome sets across all areas of health and social care [ 8 ]. Since its launch in 2010, COMET has compiled resources to help people developing core outcome sets and a freely accessible database of published core outcome studies, drawing on the aforementioned systematic review [ 7 ] and subsequent updating using the same search strategy [ 9 ]. Furthermore, recognising the challenges that people reading reports of a core outcome set face when trying to decide whether to adopt an existing core outcome set or develop a new one, work is underway to develop a reporting guideline, using an international consensus process [ 10 ]. It is also important to note that the development of a core outcome set which focuses on the what to measure may need to be followed by decisions about how and when to measure. Heterogeneity in how outcomes have been measured or the timing of those measurements can undermine efforts to facilitate the work of systematic reviewers who are trying to compare, contrast and combine the results of multiple studies even if the outcomes themselves are consistent across the studies. This is an area of ongoing collaboration between COMET and COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) [ 11 ].

Core outcome sets in systematic reviews

Currently, the explicit use of core outcome sets in systematic reviews seems rare. For example, a survey of all Cochrane Reviews that were first published in full in 2007 (387 reviews), 2011 (401), and 2013 (439) did not identify any that cited a core outcome set as influencing the choice of outcomes to investigate in the review but found that these 1227 reviews included a total of nearly 9800 outcomes [ 12 , 13 ]. Considering the new reviews from 2013 only [ 13 ], the number of specified outcomes in each review ranged from just one in three reviews to 62 in a review which examined different types of dietary advice for women with gestational diabetes and specified short- and long-term outcomes for both mother and child [ 14 ]. The median number of outcomes was 7. The 439 reviews specified a total of 3644 outcomes in their methods sections. After excluding the 65 reviews that did not have any included studies, 68 % (2134/3142) of these specified outcomes were reported in the “Results” section of the review. Of the 1008 non-reported outcomes across all reviews that had studies in them, 77 % (775/1008) had not been reported because they were not measured in the studies included in the review or insufficient data were available. No clear reason was found in the text of the review for the non-reporting of the remaining 23 % (233/1008) [ 13 ].

One of the ways in which core outcome sets might be particularly useful for Cochrane Reviews [ 15 ] and other systematic reviews is in the selection of outcomes to include in the Summary of findings tables developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group to summarise the results for important outcomes and the quality of this evidence [ 16 ]. For Cochrane Reviews, it is recommended that these tables include seven or fewer outcomes, and they have been shown to improve readers’ understanding and speed of retrieval of the findings of the review [ 17 ]. They were introduced to Cochrane Reviews in 2008 and were included in 112 (31 %) of the 361 full reviews published for the first time in 2011 and containing at least one included study, rising to 57 % (216 of 375 new reviews) in 2013 [ 13 ].

Using core outcome sets when registering a systematic review

An important opportunity for systematic reviewers to make use of core outcome sets, and to be clear about doing so, is when choosing the outcomes to assess in their review. They can make this explicit in the protocol for their review and in its prospective registration. Since its inception, Cochrane has required authors of Cochrane Reviews to have their proposed review approved by the relevant Cochrane Review Group and then prepare and publish the protocol for their review. Since 2011, it has been possible for all systematic reviewers to register their review at their outset in PROSPERO, a free-to-use registry for systematic reviews developed and run by the Centre for Reviews and Dissemination in the University of York, UK [ 18 ]. PROSPERO recorded its 10,000th entry in 2015, and as in the protocols for Cochrane Reviews, reviewers are able to list the outcomes that they will attempt to assess in the included studies in their registry entry. They could mention their intended use of a core outcome set, as we have suggested for trial registries such as International Standard Randomised Controlled Trial Number (ISRCTN) [ 3 ]. It would also allow the reviewers to specify any additional outcomes that they are interested in. Specifying the outcomes from the core outcome set, and using the terms for these outcomes that were used in that core outcome set, would facilitate searching of PROSPERO and the protocols for Cochrane Reviews. Another benefit from considering the core outcome set in the design and registration of their review is that this might help reviewers to choose the outcomes to include in a Summary of findings table. This might also help to focus their subsequent actions, including the seeking of data that are not available in the reports of eligible studies so that they obtain information that is as complete as possible for these outcomes. When others inspect the registry entry for a review, the explicit use of a core outcome set will help them to decide if the eventual review is affected by selective reporting bias because the review authors have not included all the outcomes from the core outcome set when presenting their results [ 19 ].

Systematic reviewers are often the researchers who struggle most because of inconsistencies in the outcomes that have been measured and reported in trials of health and social care. This hampers their ability to resolve the uncertainties that they seek to address in their reviews. They can help to overcome these problems by becoming involved in the development of core outcome sets and then using them as a foundation for the outcomes to include in their review and summaries, such as the Summary of findings tables [ 14 ]. We welcome comments on these suggestions and those that we made earlier for trial registries [ 3 ], with the overall intention of helping reviewers and other researchers achieve their ultimate aim of improving health and well-being through improving health and social care.

Abbreviations

Core Outcome Measures in Effectiveness Trials

Grading of Recommendations Assessment, Development and Evaluation

International Standard Randomised Controlled Trial Number

Outcome Measures in Rheumatology

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Acknowledgements

COMET has received funding from the Medical Research Council Methodology Research Programme (grant number MR/J004847/1) and European Union Seventh Framework Programme ([FP7/2007–2013] [FP7/2007–2011]) under grant agreement n° 305081.

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MC and PW are members of the COMET Management Group and co-applicants on grants to support COMET and related work.

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MC drafted the initial version of this manuscript, based on discussions with PW and others, and prepared the first revision in accordance with feedback from the journal. PW critically reviewed the initial version and revised the manuscript. Both authors read and approved this final manuscript.

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Clarke, M., Williamson, P.R. Core outcome sets and systematic reviews. Syst Rev 5 , 11 (2016). https://doi.org/10.1186/s13643-016-0188-6

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Published on 8.9.2021 in Vol 23 , No 9 (2021) : September

The Impact of Digital Patient Portals on Health Outcomes, System Efficiency, and Patient Attitudes: Updated Systematic Literature Review

Authors of this article:

• Elettra Carini 1 * , MD   ; 
• Leonardo Villani 1 * , MD   ; 
• Angelo Maria Pezzullo 1 , MD, MSc   ; 
• Andrea Gentili 1 , MD   ; 
• Andrea Barbara 2, 3 , MD   ; 
• Walter Ricciardi 1 , MD, MPH   ; 
• Stefania Boccia 1, 4 , MSc, PhD  

1 Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy

2 Hygiene and Public Health Service, ASL Roma 1, Rome, Italy

3 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy

4 Department of Women, Children and Public Health Sciences - Public Health Area, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy

*these authors contributed equally

Corresponding Author:

Angelo Maria Pezzullo, MD, MSc

Section of Hygiene

University Department of Life Sciences and Public Health

Università Cattolica del Sacro Cuore

L go F Vito 1

Rome, 00168

Phone: 39 0630154396

Email: [email protected]

Background: Patient portals are becoming increasingly popular worldwide even though their impact on individual health and health system efficiency is still unclear.

Objective: The aim of this systematic review was to summarize evidence on the impact of patient portals on health outcomes and health care efficiency, and to examine user characteristics, attitudes, and satisfaction.

Methods: We searched the PubMed and Web of Science databases for articles published from January 1, 2013, to October 31, 2019. Eligible studies were primary studies reporting on the impact of patient portal adoption in relation to health outcomes, health care efficiency, and patient attitudes and satisfaction. We excluded studies where portals were not accessible for patients and pilot studies, with the exception of articles evaluating patient attitudes.

Results: Overall, 3456 records were screened, and 47 articles were included. Among them, 11 studies addressed health outcomes reporting positive results, such as better monitoring of health status, improved patient-doctor interaction, and improved quality of care. Fifteen studies evaluated the impact of digital patient portals on the utilization of health services with mixed results. Patient characteristics were described in 32 studies, and it was reported that the utilization rate usually increases with age and female gender. Finally, 30 studies described attitudes and defined the main barriers (concerns about privacy and data security, and lack of time) and facilitators (access to clinical data and laboratory results) to the use of a portal.

Conclusions: Evidence regarding health outcomes is generally favorable, and patient portals have the potential to enhance the doctor-patient relationship, improve health status awareness, and increase adherence to therapy. It is still unclear whether the use of patient portals improves health service utilization and efficiency.

Introduction

In recent years, electronic tools that allow patients to interact with health care professionals have considerably increased with consequences on the awareness of citizens about their own health [ 1 ]. The adoption of these technologies might represent an important measure to improve the quality and efficiency of health care services and is a key feature for the construction of a more equitable, effective, and safe health care system [ 2 ]. Indeed, the rapid growth and diffusion of digital health, including health information sources, such as electronic medical records (EMRs), has made online access to information by patients and health care professionals a crucial component of health care delivery [ 3 ].

In this context, patient portals are thought to allow patients secure access to health-related information and to communicate and share information with providers [ 4 ]. Besides guaranteeing protected access to EMRs, more advanced patient portals allow secure message exchange between health professionals and citizens, consultation of educational material adapted to patients’ own characteristics, appointment scheduling, automatic renewal of medical prescriptions for chronic diseases, and facilitation of payments. Despite their potential benefits, several studies have proved underuse or inappropriate use of patient portals and their limited impact [ 5 ]. Furthermore, the majority of studies available on this topic have focused on users’ characteristics and satisfaction, and few studies have considered the consequences on health outcomes [ 6 - 8 ]. Patient portals are relatively new technologies with continuous updates. Several types are released every year, and this may explain the lack of research in this area [ 5 ].

A systematic literature review in 2013, which addressed the effect of patient portals on patient clinical care, reported that evidence was limited to evaluate whether patient portals had a positive, negative, or neutral impact on users’ health [ 4 ]. Some of the most effective examples refer to patients with chronic diseases, such as diabetes, hypertension, and depression, specifically when the portal is included in a shared health care pathway [ 9 - 13 ]. The effect of patient portals on health care utilization and efficiency, instead, is unclear due to the scarcity of studies examining the impact of patient portals on key indicators, such as inpatient hospitalizations, emergency department (ED) and outpatient visits, length of stay, and telephone contacts [ 14 ]. The aim of this systematic review was to update the study performed in 2013, by summarizing evidence on the impact of digital patient portals on patients’ health outcomes, health care efficiency, and patients’ attitudes and satisfaction.

Search Strategy

A search of relevant articles was performed in the PubMed and Web of Science databases using the query reported in Multimedia Appendix 1 . The resulting records were entered in a dedicated work sheet to be subsequently screened according to the inclusion/exclusion criteria. Following the removal of duplicates, the selection was made by reading titles and abstracts, and then the full texts.

Inclusion/Exclusion Criteria

Eligible studies were primary studies reporting on the impact of patient portal adoption in relation with health outcomes, health care efficiency, and patients’ attitudes and satisfaction. Articles included were published from January 1, 2013, to October 31, 2019, and written in English, Italian, Spanish, or French. We excluded studies describing portals that were not accessible for patients, as well as pilot studies, with the exception of studies evaluating patients’ attitudes.

Selection Process and Data Extraction

Two authors screened the articles, and each reference retrieved was screened by two researchers independently, with any disagreement finally discussed and resolved by a third researcher, if necessary. The following information was extracted from the studies: first author name, publication year, study country, study design, study population, study setting, study duration and time, health information technology, study objective, main findings according to health outcomes, health care efficiency/utilization, patient characteristics, and patient attitudes and satisfaction. The systematic literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 checklist [ 15 ].

Characteristics of the Included Studies

The database search, after duplicate removal, identified a total of 3456 records. According to the inclusion/exclusion criteria, the screening resulted in the inclusion of 47 full-text articles ( Figure 1 ).

The study designs were grouped into six categories according to the characteristics of the articles. Overall, 17 were descriptive quantitative studies [ 8 , 16 - 31 ], two were descriptive mixed-methods studies [ 32 , 33 ], 14 were observational hypothesis testing studies [ 20 , 34 - 46 ], seven were descriptive qualitative studies [ 47 - 53 ], five were interventional studies, other than randomized controlled trials (RCTs) [ 54 - 58 ], and three were RCTs [ 59 - 61 ].

With regard to country, 33 (70%) studies were based in the United States [ 17 , 18 , 20 , 21 , 31 , 32 , 34 , 43 - 46 , 49 , 60 ], three in Canada [ 35 , 36 , 50 ], three in the Netherlands [ 19 , 26 , 57 ], two in Finland [ 55 , 56 ], two in the United Kingdom [ 16 , 48 ], one in Australia [ 22 ], one in France [ 59 ], one in Israel [ 47 ], and one in Sweden [ 24 ].

Various patient portals have been described in the studies. Multimedia Appendix 2 provides details on the functionalities of the portals, and Multimedia Appendix 3 provides qualitative descriptions of the portals.

Most of the portals were not addressed to a defined population subgroup, and only some of them were specific to a clinical specialty/condition, such as endocrinology-diabetes [ 8 , 21 , 26 , 34 , 36 , 41 ], primary care [ 33 , 37 , 38 , 40 , 60 ], mental health [ 31 , 35 , 54 ], multiple chronic conditions [ 40 , 55 , 56 ], pulmonology and asthma [ 32 , 44 , 60 ], rheumatology [ 50 , 57 , 59 ], cardiology [ 37 , 44 ], internal medicine [ 40 , 61 ], nephrology [ 30 , 46 ], pregnancy [ 34 ], cancer [ 53 ], and gastroenterology [ 48 ].

The population included in the studies was heterogeneous in terms of sample size (from 24 [ 52 ] to 2,171,325 patients [ 31 ]) and groups of included patients (eg, pediatric [ 32 ], older [ 31 ], oncology [ 52 ], and diabetic patients [ 60 ]).

The results were summarized in four categories, albeit the same study could belong to more than one category. In particular, 11 studies analyzed health outcomes and adherence, intended as a change in individual or population health, attributable to health-related interventions. Adherence is the degree to which a patient follows medical advice, especially drug compliance. Overall, 15 studies focused on health care efficiency/utilization (utilization of health care services), 32 studies referred to patient characteristics, and 30 studies analyzed attitudes and satisfaction.

Health Outcomes and Adherence

Eleven articles presented results on patient outcomes ( Table 1 ), such as prevention, diabetes, blood pressure control, asthma, mental health, and medication adherence.

In particular, a significant association was found between patients’ preventive health behaviors and portal use [ 45 ]. Considering diabetes [ 34 , 36 ] and blood pressure control [ 37 ], portal users were significantly more likely to control their HbA 1c levels successfully compared to nonusers.

An improved clinical condition over time was observed in the management of asthma in children, where the group using the patient portal reported better flare control compared to the control group [ 60 ].

Concerning mental health, patients using the portal had a positive impact related to the clinical condition in many domains [ 35 ], such as the reduction of drinking days [ 54 ]. However, concerning the health status, no marked short-term impact was described, and differences in patient-reported physical and mental health changes were minor [ 55 ].

Finally, higher medication adherence was described in portal users compared with nonusers, especially among pediatric patients with asthma and patients with rheumatic disorders [ 32 , 57 ].

a PGHD: patient-generated health data.

b RCT: randomized controlled trial.

c OR: odds ratio.

d EHR: electronic health record.

e CCI: Charlson Comorbidity Index.

f eGFR: estimated glomerular filtration rate.

g PCP: primary care practice.

h BP: blood pressure.

i HR: hazard ratio.

Efficiency/Utilization

Fifteen articles described the relationship between portal use and health care service efficiency and utilization ( Table 2 ). The use of a digital portal had an effect on the utilization of health care services in terms of the number of clinical visits, especially for asthmatic patients [ 32 , 60 ], while no statistically significant changes in the number of primary care visits was reported in association with the use of secure messaging [ 38 ].

a RCT: randomized controlled trial.

b ED: emergency department.

c ASA: American Society of Anesthesiology.

d OR: odds ratio.

e ER: emergency room.

f PCP: primary care physician.

g RR: rate ratio.

Concerning emergency room (ER) visits, a decreasing trend was described [ 54 , 60 ], and active portal users showed more outpatient and inpatient visits and fewer ER visits per month, compared with patients without an account [ 28 ]. The number of visits over 6 months for asthmatic patients was lower among users than among nonusers (3 vs 9) [ 60 ]. User status was not significantly associated with ED access in the study by Plate et al, and the use of secure messages showed a nonsignificant result [ 39 ].

A reduction in hospitalizations was described for asthma [ 60 ] and mental health conditions [ 54 ]. Different findings were observed in patients with acute myocardial infarction, congestive heart failure, or pneumonia. In these cases, the odds of 30-day readmission for active users was 66% higher than that for nonusers, while no significant difference was described between nonusers and light users [ 44 ]. Considering patients who underwent total hip or knee arthroplasty, there was a significant association between 90-day readmission and sending two or more secure messages [ 39 ].

Concerning clinicians’ attitudes, the portal seemed to enable a new way of managing stable patients, facilitating clinical and cost-effective use of specialist nurses (improved two-way communication, and more optimal use of outpatient appointments and consultant time). The portal also facilitated a single rationalized pathway for stable patients, enabling access to information and proactive support [ 48 ].

Portal use by patients reduced missing appointments [ 35 ] and showed an improvement in appointment adherence after portal adoption [ 42 ]. However, no significant association between user/nonuser status and no-show appointments was found by one study [ 28 ]. The difference in cancellation rate proxies was also not significant between the user and nonuser groups [ 42 ].

Finally, concerning other aspects, only one study took into consideration the associated costs with ambiguous results. In this study, costs decreased in the unadjusted model but increased after adjusting for relevant variables [ 55 ]. An increase in HIV screening rates was described, but changes in the rates of HIV risk behaviors (eg, condom use) and modification of addiction treatments appeared nonsignificant in mental health patients [ 54 ]. Portal use had a positive effect on days of work lost due to asthma patients’ issues [ 60 ]. Moreover, information services were positively affected by portal use, as it led to a reduced number of requests [ 35 ].

Patient Characteristics

Concerning patients’ characteristics, 32 articles presented relevant results that were mainly related to demographic information, such as age, gender, education, and household status ( Table 3 ).

a OR: odds ratio.

c EHR: electronic health record.

d PHR: personal health record.

e LDL: low-density lipoprotein.

f SBP: systolic blood pressure.

g FM: family medicine.

h GIM: general internal medicine.

i ASA: American Society of Anesthesiology.

j SM: secure messaging.

k FPL: federal poverty level.

In terms of age, results were not homogeneous. Higher use in older patients (aged >50 years) was described in four studies [ 18 , 20 , 21 , 33 ]. In a middle age and elderly cohort, the mean age of users was significantly lower [ 45 ]. On the other hand, younger patients were also the major users in disease/specialty-specific cohorts [ 32 , 35 , 46 ].

A total of 19 studies mentioned the origin and ethnicity of users [ 8 , 18 , 25 , 27 , 30 - 32 , 34 , 37 - 39 , 42 - 46 , 52 , 58 ]. White patients were usually the most likely to use the portals described in the different studies [ 18 , 27 , 30 - 32 , 37 , 38 , 43 , 45 , 52 ]. Two studies found no significant association between ethnicity and portal use [ 8 , 28 ].

Most of the articles found a positive association between female gender and portal use [ 28 , 35 , 38 , 42 , 43 , 58 ]. Only one study, conversely, found male gender to be a predictor of registering [ 27 ]. No statistically significant association between sex and user/nonuser status was found in two articles [ 36 , 45 ].

In a cohort of patients with mental disorders, having schizophrenia or schizoaffective disorders was negatively associated with portal use [ 31 ]. Instead, depression was positively associated [ 37 ]. Moderate or severe asthma was more linked to portal use [ 32 , 60 ]. Moreover, having a diagnosis of diabetes, hypertension, heart failure, or cardiovascular disease was a significant predictor of portal use [ 20 , 40 ], with one exception [ 46 ]. On the other hand, there were contrasting results concerning the association between the number of comorbidities and portal use [ 27 , 37 , 41 , 42 , 44 ].

People living in rural areas were less likely to use patient portals than urban citizens in three studies [ 22 , 31 , 41 ], while higher education levels were often related to broader use of portals [ 23 , 25 - 27 , 30 , 32 , 52 , 57 ]. Only one study showed no significant association [ 8 ]. Higher income was also generally associated with portal use [ 31 , 37 , 45 , 46 , 58 ]. Only one study found no association between income and the use of secure messages [ 8 ].

Studies conducted in the United States showed that having a private insurance was positively associated with portal use [ 18 , 32 , 39 , 42 , 45 , 46 , 58 ], with only one study reporting the absence of this association [ 28 ].

Other patient characteristics positively associated with portal use were being a member of a patient association [ 59 ] and being admitted to an academic medical center [ 44 ].

Attitudes and Satisfaction

Patient attitudes were evaluated in terms of perceived barriers and facilitators toward portal use. The overall satisfaction was also assessed, and it refers to the extent to which the patient is content about health care. Thirty articles addressed these topics ( Multimedia Appendix 4 ).

Nine articles clearly addressed the barriers to portal use. Some of the main issues were related to perceived or preconceived security concerns [ 8 , 48 ], limited knowledge [ 26 , 51 ], satisfaction with current care [ 51 ], paying for the service [ 54 ], disinterest in managing one’s own disease [ 26 , 57 ], personal/time constraints and not thinking about accessing the portal [ 57 , 61 ], doubts about the reliability of the patient portal to facilitate a timely and productive message exchange with providers [ 8 ], and prior negative experiences with secure messaging [ 8 ]. Other barriers were related to population characteristics, such as being a clinician older than 55 years or younger than 35 years and being male [ 33 ], and variation in provider availability for online appointment scheduling and response times to medical messages [ 25 ]. Limited computer and internet access [ 20 , 25 , 26 , 51 , 57 ], knowledge of technology [ 25 , 26 , 57 ], security concerns [ 25 , 48 ], and data integration [ 48 ] were also negative predictors of portal use.

On the other hand, nine articles specified the elements that facilitated portal use, including improved communication with specialists [ 22 , 48 , 60 ]; availability of information that led to an increased awareness of the health status [ 19 , 22 , 32 , 51 , 60 ] and tracking of disease control [ 32 ]; time-saving, convenient, and easy to use elements [ 19 ]; accuracy, timeliness, usefulness, and convenience of the functionalities included in the portal [ 22 , 50 ]; availability of surrogates (ie, daughter or family member) to act as intermediaries [ 51 ]; active involvement of the practice/staff in the promotion of the portal (ie, team approach strategy to engage staff in notifying patients) [ 33 ]; and active training of the patient for portal use [ 61 ]. Concerning satisfaction, patients were generally satisfied with the portals [ 8 , 17 , 21 , 29 , 49 , 50 , 59 - 61 ].

Due to the considerable amount of literature published on the topic of patient portals, the aim of this review was to provide evidence and to gather information systematically. Similar to the review published in 2013 by Goldzweig et al [ 4 ], the outcomes were grouped into four aspects, namely, health outcomes and adherence, health care efficiency, patient characteristics, and attitudes and satisfaction, and showed nonunique results in terms of benefits brought by patient portals concerning patient experience and health. The functionalities available in the portals described by Goldzweig et al and our review were likewise the same.

Positive results were described relating to the enhancement of preventive behaviors [ 45 ], changes in chronic condition control with higher control of diabetes parameters [ 34 , 36 ], and asthma flares [ 60 ]. However, conflicting results were described concerning blood pressure control [ 34 , 37 ], mental health conditions [ 35 , 54 , 55 ], and medication adherence [ 32 , 57 ]. A possible explanation of these results is that these particular studies involved patients (often with a low sample size) who utilized portals for a short period of time, preventing them from having a possible consistent outcome. Similarly, concerning health outcomes, Goldzweig et al found generally positive results, which documented improvement in patients’ disease control and maintenance [ 4 ], even though many of the included studies in our review did not find a significant difference between portal users and nonusers. Adherence to therapy was always improved [ 4 ] similar to that in this review.

The number of clinical and ED visits [ 28 , 32 , 39 , 54 , 60 ] and hospital readmissions [ 39 , 44 , 54 , 60 ] did not always decline in patients using portals. The number of missed appointments decreased [ 35 , 42 ], but this finding was not always significant [ 28 , 42 ]. The nondeclining trends of hospitalizations and outpatient visits as a consequence of portal use are concordant in the two studies, although different findings were described. Indeed, different from our review, in which we found more often a decrease in the utilization of in-person services, the review by Goldzweig et al reported that most of the studies found an increased number of outpatient visits and hospitalizations. As patient portals are normally designed to reduce inappropriate health care utilization, this might be partially explained by the fact that provider and patient adaptations to the patient portals have evolved over time.

The studies differed also in terms of the population included, with conflicting results in portal adoption and age, gender, ethnicity, kind of disease, and number of comorbidities. Generally, having a higher income [ 31 , 37 , 45 , 46 , 58 ] and having a private insurance were associated with increased portal use [ 18 , 32 , 39 , 42 , 45 , 46 , 58 ].

The main barriers faced in using the portals were (1) user-related issues, such as time constraints [ 57 , 61 ], disinterest in managing the disease [ 26 , 57 ], and limited digital knowledge [ 26 , 51 ]; (2) clinician-related issues, such as age [ 33 ] and attitude toward the portal [ 33 ]; and (3) technology-related issues, such as limited internet access [ 25 , 26 , 51 , 57 ] or ability to use technology [ 25 , 26 , 57 ] and security concerns [ 25 , 48 ]. Privacy and security concerns, and ability to use technological appliances and systems were the most important barriers to utilization described in the studies retrieved by Goldzweig et al [ 4 ]. Indeed, other recent reviews on patient attitudes highlighted that privacy and security problems are the main barriers to the use of patient portals. These barriers are as evident in elderly patients (in whom there is also a limitation of portal use related to age) as in younger patients [ 62 , 63 ]. Moreover, technical problems due to patient capacity and difficulties in using the portal also represent important barriers. Thus, correct and adequate information on safety issues and education on the technical use of the portal represent the best facilitators. Furthermore, engaging patients and making them realize that the portal represents a useful tool to support the management of their pathology (especially for chronic diseases) without replacing the doctor-patient relationship are important to encourage the use of digital portals [ 13 , 62 , 64 ]. In addition, technical improvements in the usability of portals could increase patient enrollment.

Security problems are complex issues that must be considered in any part of medical care. The use of information technologies in health care that can be accessed by multiple types of users (physician, patient, caregiver, and hospital administrative staff) represents the basis of the discussion about computer security [ 65 ]. Indeed, uncertainties about security of clinical data might hinder adoption of systems by both hospitals and patients [ 48 ]. Patients expressed concern about their privacy and the privacy of their family members, and asked for further information about confidentiality, as vulnerable data might be accessed by external providers, such as insurance providers, who are the main actors of health care access in many countries [ 47 ].

The facilitators retrieved were the prompt availability of health information that caused an increase in the awareness of the health status [ 19 , 22 , 32 , 51 , 60 ], improved communication with health care professionals [ 22 , 48 , 60 ], and the accuracy, timeliness, usefulness, and convenience of the functionalities included in the portal [ 22 , 50 ]. In this latter argument, some functionalities of the portal were found to be more useful than others, including laboratory tests and imaging [ 23 , 24 , 29 , 43 , 52 ], medical notes [ 23 , 26 ], messaging with providers [ 52 ], medication refill [ 52 ], and current medication list [ 29 ]. Generally and as observed by Goldzweig et al [ 4 ], patients declared being satisfied with the use of digital tools [ 8 , 17 , 21 , 29 , 49 , 50 , 59 - 61 ].

Despite the considerable number of studies included, the high heterogeneity in terms of outcomes and described portal functionalities did not allow us to perform meta-analyses and to draw generalizable and strong conclusions concerning the utility of the unique features of the portals.

Technological and digital innovations in health care could contribute to achieving the health system goals of equity, efficiency, accessibility, quality, and sustainability, if they are purposefully designed and cost-effectively implemented. When designing a new patient portal or a new functionality, developers and providers should always consider to which health care need they are trying to respond and if other nondigital interventions may be more effective or as effective at a lower cost.

Moreover, the adoption of a new technology is a complex process, depending on the content and the context in which it is introduced. As an example, our review demonstrated that it is feasible to achieve better medication adherence in chronic disease patients through portal use, and highlighted the main facilitators (eg, prompt availability of reliable information and accessibility of communication with disease specialists) and barriers (eg, security and usability concerns, and limited digital knowledge) to portal use. Keeping in mind these contextual factors could ease the difficult task of identifying the best digital tool for a specific population.

Before designing or implementing a new tool, it can be useful to analyze the ideal conditions needed for the adaptation, transfer, absorption, up-scaling, and enhancement of digital technologies. By ideal conditions, we basically mean a situation where the new technology has demonstrated effectiveness in trials or pilots, the provider is committed to guarantee continuous improvement in user accessibility and usability, and the main barriers in the target population are given due consideration. In the absence of these conditions, satisfactory results may be difficult to reach or may take many years to be observed.

The benefits of digitalization cannot be taken for granted and the use of technology does not always lead to an improvement in patient care and health system performance; thus, there is a need for evidence, which is, to date, scarce. The identification of a set of main features with proven efficacy for a patient portal is a useful starting point for the development and implementation of patient-oriented portals. Further studies should be conducted in different aspects of digitalization in health care. None of the studies retrieved analyzed the cost-effectiveness of portal use. Similarly, none of the studies compared the portals to each other, which could be interesting to point out the best practices and features.

Even though a patient portal is not a new concept, its real utilization and implementation are still far from optimal, and it seem to be still considered a “future technology.” It is important to adapt the portal functions to the needs and capacities of patients, in order to facilitate the use of this technology and improve its dissemination. In particular, overcoming ethnic and literacy barriers to portal use represents a fundamental goal to create more equitable, effective, and safe health care systems.

Authors' Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by EC, LV, AMP, AG, and AB. EC and LV screened the articles, with any disagreement finally discussed and resolved with AMP. The first draft of the manuscript was written by EC, LV, AMP, AG, and AB. WR and SB commented on the latest version of the manuscript. WR and SB supervised the study. All authors read and approved the final manuscript.

Conflicts of Interest

None declared.

Search string.

Functions and details of patient portals.

Qualitative descriptions of the portals and/or features studied in the included articles.

Summary of the findings on patient attitudes and satisfaction.

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Abbreviations

Edited by R Kukafka; submitted 03.12.20; peer-reviewed by S Pillon, N Gordon, I Wilson, F Kaliyadan; comments to author 10.01.21; revised version received 24.01.21; accepted 24.05.21; published 08.09.21

©Elettra Carini, Leonardo Villani, Angelo Maria Pezzullo, Andrea Gentili, Andrea Barbara, Walter Ricciardi, Stefania Boccia. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.09.2021.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.

• Introduction
• Conclusions
• Article Information

Dark blue boxes indicate RRs, and horizontal bars indicate 95% CIs. Sizes of dark blue boxes are proportional to the inverse variance. The light blue diamond indicates the pooled RR estimate and 95% CI in the random-effects model meta-analysis. RRs are maximally adjusted estimates as reported by studies (see eTable 1 in Supplement 1 for adjustment variables). Badr et al 32 for RR of all-cause death and Postigo et al 28 for RR of MACE were crude estimates calculated by this study’s authors based on number of participants and number of events reported for patients living with HIV and control groups. The definition of MACE for Shitole et al 18 and Postigo et al 28 was death or cardiovascular admissions.

RRs are shown for recurrent acute coronary syndrome (ACS) (A), heart failure (HF) admission (B), cardiovascular (CV) death (C), and restenosis (D). Dark blue boxes indicate RRs, and horizontal bars indicate 95% CIs. Sizes of dark blue boxes are proportional to the inverse variance. The light blue diamond indicates the pooled RR estimate and 95% CI in the random-effects model meta-analysis.

eTable 1. Additional Patient Characteristics by Study for Patients Living With HIV and Patients in Control Groups

eTable 2. Comparison of Patient Characteristics Between Patients Living With HIV and Patients in Control Groups

eTable 3. Clinical Outcomes, Relative Risks, and Adjustment Variables by Study

eTable 4. Sensitivity Analysis of Pooled Relative Risks Calculated Using Knapp-Hartung Method for Random-Effects Model Meta-Analysis

eTable 5. Quality Assessment of Included Studies With Newcastle-Ottawa Scale

eFigure 1. Study Flow Sheet

eFigure 2. Pooled Relative Risks for Patients Living With HIV vs Patients in Control Groups for TLR and TVR

eFigure 3. Pooled Unadjusted Relative Risks for Patients Living With HIV vs Patients in Control Groups for All-Cause Mortality, MACE, and Recurrent ACS

eFigure 4. Funnel Plot of Relative Risks for All-Cause Mortality and MACE

eMethods. Detailed Description of Statistical Analysis

Data Sharing Statement

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Haji M , Capilupi M , Kwok M, et al. Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV : A Systematic Review and Meta-Analysis . JAMA Netw Open. 2024;7(5):e2411159. doi:10.1001/jamanetworkopen.2024.11159

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Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV : A Systematic Review and Meta-Analysis

• 1 Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island
• 2 Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri
• 3 Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina
• 4 Global Health Institute, University of Washington, Seattle
• 5 Infectious Disease Section, Michael E. DeBakey VA Medical Center, Houston, Texas
• 6 Department of Medicine, Baylor College of Medicine, Houston, Texas
• 7 Pharmacy Service, Michael E. DeBakey VA Medical Center, Houston, Texas
• 8 Center of Innovation, Providence VA Medical Center, Providence, Rhode Island
• 9 Evidence Synthesis Program Center, Providence VA Health Care System, Providence, Rhode Island
• 10 Department of Medicine, Providence VA Medical Center, Providence, Rhode Island
• 11 Department of Pharmacy, University of Rhode Island, Providence
• 12 Department of Health Services, Policy and Practice, Brown University, Providence, Rhode Island

Question   What are the postdischarge outcomes for patients living with HIV after acute coronary syndromes or coronary revascularization?

Findings   In this systematic review and meta-analysis of 15 studies involving 9499 patients living with HIV and 1 531 117 patients without HIV, patients living with HIV had a higher risk of all-cause mortality, major adverse cardiovascular events, recurrent acute coronary syndromes, and admission for heart failure after the index event, despite being approximately 11 years younger at the time of the event. Patients living with HIV were more likely to be current smokers and engage in illicit drug use and had higher triglyceride and lower high-density lipoprotein cholesterol levels than those without HIV.

Meaning   This analysis highlights the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Importance   Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

Objective   To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

Data Sources   Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

Study Selection   Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event.

Data Extraction and Synthesis   Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis.

Main Outcome and Measures   The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure.

Results   A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62).

Conclusions and Relevance   These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

The widespread use of effective antiretroviral therapies (ARTs) has led to increased survivorship among people living with HIV. Therefore, people living with HIV are experiencing an increased prevalence of age-related disease, such as cardiovascular disease (CVD). 1 , 2 The increase in CVD in this population has been attributed to multiple factors, including increasing age, the increase in burden of traditional CVD factors and psychosocial risk factors, the long-term metabolic effects of ART, and the low-grade immune activation of chronic HIV. 1 , 3 - 8

Epidemiological studies have shown that compared with populations without HIV, people living with HIV have a higher risk of coronary artery disease, acute coronary syndromes (ACS), and heart failure, with onset at younger ages. 4 , 9 - 12 Given this earlier emergence of CVD among people living with HIV, there has been significant attention and evidence generated for primary prevention strategies involving statins. 13 , 14 In conjunction with these studies, characterization of longitudinal CVD outcomes is important to identify strategies for secondary prevention and further improve survivorship among people living with HIV. Studies on clinical outcomes after ACS and percutaneous coronary interventions (PCIs) among patients living with HIV have shown higher rates of recurrent coronary disease and mortality compared with patients in HIV-negative control groups. 11 , 15 - 17 However, this association has not been characterized in sufficient detail in current literature, and extant data have not been adequately synthesized. We conducted a systematic review and meta-analysis of longitudinal studies of patients living with HIV after ACS or PCIs to better characterize clinical outcomes and postdischarge treatment compared with patients in HIV-negative control groups.

We report this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline. This study was not preregistered. Please see the eMethods in Supplement 1 for a detailed description of methods used in this meta-analysis, as recommended by the International Committee of Medical Journal Editors.

We searched Ovid MEDLINE, Embase, and Web of Science for all available articles from inception to August 2023 for the key terms coronary artery disease , myocardial infarction , non-fatal myocardial infarction , acute coronary syndrome , revascularization , percutaneous coronary intervention , and secondary prevention . We also reviewed references of relevant articles.

Articles were screened by 2 reviewers (M.H. and M.C.) by title and abstract and later by full text. We included studies if they fulfilled the following criteria: patients living with HIV and a comparator group of patients without HIV (control group) included, patients with obstructive coronary artery disease presenting with ACS or undergoing revascularization through PCI included, and longitudinal follow-up data on clinical outcomes after initial event collected. We initially also searched for studies that discussed outcomes after stroke and peripheral artery disease.

We extracted the following data where available using standardized forms: study characteristics, baseline demographics (ie, age, sex, and race and ethnicity) and other characteristics (ie, underlying comorbidities, revascularization strategies, and postdischarge medications) of HIV-positive and HIV-negative control populations, HIV-specific characteristics (use of ART, CD4 count, and viral load), number of events by group and hazard ratios (HRs) of clinical outcomes (ie, all-cause mortality, major adverse cardiovascular events [MACE], cardiovascular death, recurrent ACS, stroke, total lesion revascularization, total vessel revascularization, and admission for heart failure). We extracted maximally adjusted HRs where available, as well as unadjusted (crude) or minimally adjusted HRs for clinical outcomes. We captured data on race and ethnicity to help assess the full scope of diversity among patients living with HIV and how applicable our data may be within the global population of people living with HIV. Race and ethnicity were self-reported in the study by Shitole et al. 18 In the other studies reporting this information, data were obtained from review of medical records, including electronic health records. Reported race and ethnicity categories included African American, American Indian, Asian, Hispanic, Pacific Islander, White, and other. We primarily report aggregated data for Black, White, and Hispanic populations only given that there were limited data available on other races and ethnicities.

We combined summary study characteristics (eg, mean age, percentage male and female, percentage Black and White, and percentage Hispanic) across studies using study sizes as analytical weights to provide estimates of pooled means or percentages. The δ and P values comparing summary study-level characteristics (means or prevalences pooled across studies) between HIV-positive and HIV-negative groups were calculated from a linear regression model of each variable on HIV status weighted by the number of participants for each study (ie, a fixed-effects meta-regression). When HRs were not reported, we calculated crude risk ratios from the number of events in each group. In 2 studies, 15 , 19 data were reported as odds ratios. We pooled HRs of clinical outcomes across studies using a random-effects model meta-analysis, estimating between-study heterogeneity using the DerSimonian-Laird method. 20 As a sensitivity analysis, we also estimated between-study heterogeneity using the residual maximum likelihood method and calculated variances ( P values and CIs) of pooled relative risk (RR) estimates using modifications proposed by Knapp and Hartung. 21 For the purpose of the meta-analysis, we considered odds ratios, risk ratios, and HRs as equivalent measures of RR.

We assessed between-study heterogeneity using the Cochran Q statistic and I 2 statistic, which estimates the percentage of total variation across studies due to true between-study difference rather than chance. 22 , 23 We did not explore heterogeneity further owing to the limited numbers of studies available for most comparisons.

The quality of included studies was assessed using the Newcastle-Ottawa Scale for cohort studies. 24 We visually inspected funnel plots to assess the risk of publication bias. We also performed the Egger test for small study bias, although this was limited by the small number of studies that were generally available for investigated outcomes. Where there were P values trending toward small study bias, we performed trim and fill analyses to help assess the impact of the bias on pooled estimates (even if Egger test P values did not reach statistical significance). A 2-sided P value less than .05 was considered statistically significant. For the meta-analysis of RRs, we report point estimates and 95% CIs. All analyses were performed using Stata software statistical software version 15 (StataCorp).

An initial search yielded 3263 studies, which were screened using titles, abstracts, and full texts. Studies reviewing patient outcomes after diagnoses and interventions of peripheral artery disease and stroke were limited, reporting mainly in-hospital outcomes, short-term follow-up, or results without non-HIV comparator groups, and were not further considered in this meta-analysis. We identified 15 studies 11 , 15 , 16 , 18 , 25 - 35 of post-ACS or revascularization outcomes from 2003 to 2023 that met inclusion criteria (eFigure 1 in Supplement 1 ). Of identified studies, 2 were abstracts. 30 , 31 All were retrospective cohort studies except for 3 prospective studies ( Table 1 ). 11 , 26 , 30

Details of patient characteristics and outcomes by study are presented in Table 1 and eTable 1 in Supplement 1 . A total of 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years; pooled proportion [range], 10.1% [95% CI, 7.0%-62.5%] Black; 8.1% [95% CI, 0.4%-54.6%] Hispanic, and 13.1% [95% CI, 7.2%-64.0%] White) and 1 531 117 patients in control groups without HIV (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years; pooled proportion [range], 3.3% [95% CI, 2.5%-21.4%] Black, 3.6% [95% CI, 0.7%-36.3%] Hispanic, and 21.1% [95% CI, 14.3%-68.0%] White) who experienced ACS or underwent coronary revascularization were included in the meta-analysis. Summary baseline characteristics of study participants and comparisons of patients living with HIV with patients in control groups are presented in Table 2 and eTable 2 in Supplement 1 . The mean age of patients living with HIV was 11.1 years (95% CI, 6.2-16.0 years) less than that of patients in HIV-negative control groups ( P  < .001). HIV-positive and control populations were similarly male dominant. Patients living with HIV were statistically significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers; P  < .001) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use; P  < .001) and had significantly higher pooled mean (range) triglyceride (233 [167-268] vs 171 [148-220] mg/dL; P  = .01) and lower pooled mean (range) high-density lipoprotein cholesterol (40 [26-43] vs 46 [29-46] mg/dL; P  = .03) levels. (To convert triglycerides and cholesterol to millimoles per liter, multiply by 0.0113 and 0.0259, respectively.) There were similar proportions of patients with diabetes, hypertension, and a family history of coronary artery disease in the 2 groups ( Table 2 ; eTable 2 in Supplement 1 ).

Patients with HIV had been diagnosed with HIV for a pooled mean (range) of 11.2 (8.5-12.0) years. From 9 studies 11 , 16 , 18 , 26 , 28 , 29 , 31 , 34 , 35 that provided these data, a pooled proportion (range) of 75.2% (50.0%-94.1%) of patients living with HIV were receiving ART and 47.6% (25.0%-85.6%) had previously received protease inhibitor therapy. The pooled mean (range) CD4 count was 377 (318-462) cells/mm 3 among patients living with HIV, and most of these patients (pooled proportion [range], 77.8% [63.3%-94.6%]) had a viral load less of than 200 copies per mL ( Table 2 ).

Among 13 studies 11 , 15 , 16 , 18 , 25 - 29 , 31 - 34 that reported data on ACS, patients living with HIV and those in control groups presented similarly with ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, and unstable angina. Additionally, the groups received PCIs or coronary artery bypass graft surgery at similar proportions. After revascularization, pooled mean (range) left ventricular ejection fraction values were similar between groups (49.4% [44.0%-55.4%] vs 50.9% [48.0%-54.8%]). On postdischarge follow up, patients living with HIV had a lower proportion (range) of statin (53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescription compared with patients in control groups, but these differences were not statistically significant ( Table 2 ; eTable 2 in Supplement 1 ).

Over a pooled mean (range) follow-up of a mean of 16.2 (3.0-60.8) months after ACS or revascularization, patients living with HIV had a significantly higher adjusted risk of all-cause mortality (pooled adjusted RR, 1.64; 95% CI, 1.32-2.04), MACE (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and heart failure readmission (RR, 3.39; 95% CI, 1.73-6.62) ( Figure 1 ), as well as restenosis (RR, 2.40; 95% CI, 1.13-5.09) ( Figure 2 ) compared with patients in HIV-negative control groups (pooled mean [range] follow-up, 11.9 [3.0-60.8] months). For CV death, total vessel revascularization, and total lesion revascularization, pooled HRs showed no significantly higher risk among patients living with HIV compared with patients in control groups (eFigure 2 in Supplement 1 ). RRs of clinical outcomes and adjustment variables included in multivariate models that were reported by each study are presented in eTable 3 in Supplement 1 . Sensitivity analyses specifying an alternative method for the random-effects model yielded comparable results (eTable 4 in Supplement 1 ). In a separate subsidiary analysis, there was no association between HIV status and risk of post–ACS or PCI mortality, recurrent ACS, or MACE outcomes in the unadjusted (minimally adjusted in some studies) model (eFigure 3 in Supplement 1 ).

There was generally low heterogeneity across studies for most outcomes ( Figure 1 and Figure 2 ). Visual inspection of the funnel plot for publication bias assessment and Egger tests did not suggest the presence of significant publication bias (eFigure 4 in Supplement 1 ). For the all-cause mortality outcome, the Egger test for bias was borderline, and so we performed trim and fill analysis; this yielded similar results (RR, 1.61; 95% CI, 1.30-2.00). Included studies were of moderate to high quality based on the Newcastle-Ottawa Scale, indicating a low to moderate risk of bias (eTable 5 in Supplement 1 ).

We performed a literature-based systematic review and meta-analysis of 15 studies of longitudinal clinical outcomes after ACS or revascularization from 2003 to 2023, comprising a total of 9499 patients living with HIV and 1 531 117 patients without HIV in control groups. We found that patients living with HIV were younger and had a higher risk of all-cause mortality, MACE, recurrent ACS, and heart failure after the index event. We also noted lower rates of statin and β-blocker prescription after discharge among patients living with HIV. Overall, these findings highlight the need to develop and implement strategies for secondary prevention of CVD among patients living with HIV.

The increased mortality, recurrence of ACS, and heart failure admissions among patients living with HIV may be attributed to increased traditional CVD risk factors, psychosocial factors, HIV-related chronic inflammation, and long-term effects of ART. 11 , 16 These factors are equally difficult to control after an initial coronary event. 19 , 35 , 36 The study by Boccara et al 11 from 2020 compared its findings with those of their first, 2011 study 37 and noted an increased rate of recurrence of ACS in patients living with HIV; the authors also noted persistent smoking and chronic inflammation as factors associated with some of the greatest increases in risk for recurrent disease. This further reinforces the need for a multifaceted approach to secondary prevention.

Of note, our study found suboptimal statin prescription in patients living with HIV after ACS or revascularization, which is consistent with results of other retrospective studies. 11 , 18 , 19 , 26 , 28 , 38 - 42 These findings and those of the Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults (REPRIEVE) trial, 14 which demonstrated the benefits of pitavastatin for primary prevention of atherosclerotic cardiovascular disease among patients living with HIV, highlight the need for a concerted effort to improve guideline-directed statin prescription and adherence among these patients. 43 Additionally, the higher prevalence of smoking and higher triglyceride levels we found among patients living with HIV highlight areas for optimization, with the goal of improving secondary prevention of atherosclerotic cardiovascular disease. Differences in statin and β-blocker prescriptions on follow-up were not statistically significant, although patients living with HIV had numerically lower percentages for both outcomes.

Our pooled estimates for postdischarge antiplatelet therapy are influenced by the study from Parks et al, 33 which defined antiplatelet use as a filled prescription for clopidogrel, ticagrelor, prasugrel, or ticlopidine and as a retrospective observational study, could not reliably exclude patients with type 2 myocardial infarctions who would not typically qualify for these therapies. In that study’s sensitivity analyses of patients who received coronary angiography, percentages of patients with postdischarge antiplatelet therapies were significantly higher. We performed an analysis of aggregate postdischarge antiplatelet therapy rates excluding data from Parks et al, 33 and aggregate data for postdischarge antiplatelet therapy was much higher.

Few studies reported race or ethnicity of participants, leading to overall low aggregate percentages of White and Black patients living with HIV in our analysis, which is not representative of the global population of these patients. Race and ethnicity in most studies were obtained from review of electronic health records, except in the study by Shitole et al, 18 in which race and ethnicity were self-reported. The analysis of race and ethnicity was skewed by 2 studies; in 1 study, 44 most of the population’s race and ethnicity was unknown, and in the other study, 19 the population was mainly Hispanic. Likewise, the percentage of patients who underwent PCIs was lower than expected for a typical population presenting with ACS. This was also contributed by the Parks et al study, 33 which included patients with type 2 myocardial infarctions, who were not candidates for PCIs in their analysis.

Most studies in our analysis included patients receiving ART with low viral loads and CD4 counts greater than 200 cells/mm 3 , indicating patients with good control of their HIV disease, who are representative of people living with HIV in the current era. 1 , 4 , 7 , 45 We found 8 studies 11 , 16 , 26 - 28 , 31 , 34 , 35 that reported use of protease inhibitors among approximately 50% of patients living with HIV (47.6%). Protease inhibitors are known to have metabolic effects associated with CVD, presenting a plausible explanation for the difference in hypertriglyceridemia between patients living with HIV and patients without HIV in our study. 46 Modern ART regimens have transitioned away from the use of protease inhibitors and now include integrase inhibitors. 7 Conflicting data have emerged around the possible association of integrase inhibitors with increased incidence of CVD. 47 , 48 Therefore, further research on long-term outcomes associated with ART will be essential to primary and secondary prevention of CVD among patients living with HIV.

The period after ACS or PCI provides additional opportunity to introduce aggressive interventions to improve CVD risk factors in patients living with HIV, and these interventions may involve multidisciplinary teams. Ensuring access to and engagement of cardiologists for patients living with HIV will be important to improve outcomes, especially among underrepresented racial and ethnic minorities. 49 Input from pharmacists can also help with optimal selection of statin types, other lipid-lowering agents, and dosages to avoid drug interactions and drug-related adverse effects and maximize adherence to these therapies. Additionally, input from addiction medicine specialists and psychologists can help address underlying mental health disorders (eg, depression and anxiety) and behavioral risk factors (eg, smoking, alcohol use, and cocaine use). In our study, patients living with HIV were more likely to be smokers and engage in illicit drug use, similar to contemporary studies that also show that these behaviors are associated with an overall increased mortality in patients living with HIV despite adequate control of their underlying infection. 50 Likewise, assistance from social workers can help to mitigate social determinants associated with diet and the ability to afford crucial medications. 36 , 51 - 53 Addressing this latter aspect is critically important to improve secondary outcomes of CVD in patients living with HIV because despite increased prescription rates for cardioprotective medications, patients living with HIV have been found to be less likely to fill these medications. 38 , 42 , 52 A multifaceted or multidisciplinary intervention to address psychosocial barriers to cardiovascular care may have the potential to limit mortality and morbidity after ACS or PCI for patients living with HIV.

The findings of this meta-analysis should be considered in context of several limitations. First, given that this was a literature based meta-analysis of aggregate published data, we were unable to compare the association between HIV status and CVD outcomes by clinically important subgroup, such as age, race and ethnicity, or sex. Second, the degree of adjustment for confounders in RR estimates is limited to what is reported in individual studies, is not consistent across studies, and may be inadequate overall. For instance, very few studies accounted for HIV-specific characteristics. However, the goal of the meta-analysis was to understand the difference in secondary CVD outcomes stratified by HIV status regardless of factors that may be contributing to them. We also performed a comparison between maximally adjusted and unadjusted or minimally adjusted RRs to provide further insight into the association. Our analysis showed that there was no association between HIV status and post-ACS or -PCI mortality, recurrent ACS, or MACE outcomes in the unadjusted model. This is likely due to the reverse confounding effect of age given that patients living with HIV were significantly younger than patients in control groups, with a difference of 11 years in pooled mean age across studies. Third, most studies included in this review evaluated patients living with HIV who lived in high-income countries, which may limit generalizability to the global population of patients living with HIV. Fourth, we were not able to perform subgroup analyses of patients who had ACS and were treated medically vs PCI, as well as those who received PCI for stable coronary disease, because these data were not reported separately. Future assessment of outcomes within these subgroups would be important for preventative efforts. Fifth, we were unable to identify timelines for prescription of or adherence to ART or cardioprotective medications based on these aggregate data. Understanding these trends will also be an important focus for secondary prevention in future studies.

In this literature based systematic review and meta-analysis of longitudinal studies from 2000 to 2023, we found that patients living with HIV were significantly younger than patients in control groups. Patients living with HIV had a significantly higher risk of all-cause mortality, MACE, recurrent ACS, and admission for heart failure after the index event compared with patients in control groups.

Patients living with HIV were also significantly more likely to be current smokers and engage in illicit drug use and had higher triglyceride levels at baseline. As more data emerge for primary prevention, this analysis highlights the need for optimization of secondary prevention strategies to address poor outcomes of CVD among patients living with HIV. Future studies can focus on assessing the role of aggressive interventions, including use of multidisciplinary teams to target important risk factors and improve prescription of and adherence to cardioprotective medications among patients living with HIV after ACS or PCI.

Accepted for Publication: March 7, 2024.

Published: May 14, 2024. doi:10.1001/jamanetworkopen.2024.11159

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Haji M et al. JAMA Network Open .

Corresponding Author: Sebhat Erqou, MD, PhD, Department of Medicine, Providence VA Medical Center, 830 Chalkstone Ave, Providence, RI 02908 ( [email protected] ).

Author Contributions: Drs Haji and Erqou had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Haji, Ashong, Richard, Wu, Erqou.

Acquisition, analysis, or interpretation of data: Haji, Capilupi, Kwok, Ibrahim, Bloomfield, Longenecker, Rodriguez-Barradas, Jutkowitz, Taveira, Sullivan, Rudolph, Wu, Erqou.

Drafting of the manuscript: Haji, Capilupi, Kwok, Taveira, Erqou.

Critical review of the manuscript for important intellectual content: Capilupi, Kwok, Ibrahim, Bloomfield, Longenecker, Rodriguez-Barradas, Ashong, Jutkowitz, Taveira, Richard, Sullivan, Rudolph, Wu.

Statistical analysis: Kwok, Erqou.

Obtained funding: Erqou.

Administrative, technical, or material support: Haji, Capilupi, Kwok, Jutkowitz, Sullivan, Rudolph, Wu.

Supervision: Bloomfield, Taveira, Richard, Rudolph, Wu, Erqou.

Conflict of Interest Disclosures: Dr Longenecker reported receiving personal fees from Theratechnologies advisory board outside the submitted work. Dr Jutkowitz reported receiving grants from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development during the conduct of the study. Dr Rudolph reported receiving grants from the National Institute on Aging during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by a VISN 1 Career Development Award from the Department of Veterans Affairs, Veterans Health Administration, to Dr Erqou. Dr Erqou was also funded by the Center for Aids Research, Rhode Island Foundation, and Lifespan Cardiovascular Institute. Drs Sullivan, Rudolph, and Wu were funded by grants CIN 13-419 and C19-20-213 from the VA Health Services Research and Development Center of Innovation in Long Term Services and Supports.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

Data Sharing Statement: See Supplement 2 .

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Research Article

The occurrence of and factors associated with mental ill-health amongst humanitarian aid workers: A systematic review and meta-analysis

Roles Conceptualization, Formal analysis, Methodology, Writing – original draft

Affiliation Centre for Maternal and Newborn Health, Liverpool School of Tropical Medicine, Liverpool, United Kingdom

Roles Writing – original draft, Writing – review & editing

Affiliation Liverpool Women’s Hospital NHS Foundation Trust, Liverpool, United Kingdom

Affiliation Independent Consultant in Global Health, United Kingdom

Roles Conceptualization, Supervision, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

• Lily Cameron, 
• Mary McCauley, 
• Nynke van den Broek, 
• Hannah McCauley

• Published: May 15, 2024
• https://doi.org/10.1371/journal.pone.0292107
• Reader Comments

Humanitarian crises and disasters affect millions of people worldwide. Humanitarian aid workers are civilians or professionals who respond to disasters and provide humanitarian assistance. In doing so, they face several stressors and traumatic exposures. Humanitarian aid workers also face unique challenges associated with working in unfamiliar settings.

To determine the occurrence of and factors associated with mental ill-health among humanitarian aid workers.

Search strategy

CINAHL plus, Cochrane library, Global Health, Medline, PubMed, Web of Science were searched from 2005–2020. Grey literature was searched on Google Scholar.

Selection criteria

PRISMA guidelines were followed and after double screening, studies reporting occurrence of mental ill-health were included. Individual narratives and case studies were excluded, as were studies that reported outcomes in non-humanitarian aid workers.

Data analysis

Data on occurrence of mental ill-health and associated factors were independently extracted and combined in a narrative summary. A random effects logistic regression model was used for the meta-analysis.

Main results

Nine studies were included with a total of 3619 participants, reporting on five types of mental ill-health (% occurrence) including psychological distress (6.5%-52.8%); burnout (8.5%-32%); anxiety (3.8%-38.5%); depression (10.4%-39.0%) and post-traumatic stress disorder (0% to 25%). Hazardous drinking of alcohol ranged from 16.2%-50.0%. Meta-analysis reporting OR (95% CI) among humanitarian aid workers, for psychological distress was 0.45 (0.12–1.64); burnout 0.34 (0.27–0.44); anxiety 0.22 (0.10–0.51); depression 0.32 (0.18–0.57) and PTSD 0.11 (0.03–0.39). Associated factors included young age, being female and pre-existing mental ill-health.

Conclusions

Mental ill-health is common among humanitarian aid workers, has a negative impact on personal well-being, and on a larger scale reduces the efficacy of humanitarian organisations with delivery of aid and retention of staff. It is imperative that mental ill-health is screened for, detected and treated in humanitarian aid workers, before, during and after their placements. It is essential to implement psychologically protective measures for individuals working in stressful and traumatic crises.

Citation: Cameron L, McCauley M, van den Broek N, McCauley H (2024) The occurrence of and factors associated with mental ill-health amongst humanitarian aid workers: A systematic review and meta-analysis. PLoS ONE 19(5): e0292107. https://doi.org/10.1371/journal.pone.0292107

Editor: Natasha Khamisa, University of the Witwatersrand, SOUTH AFRICA

Received: February 22, 2022; Accepted: September 13, 2023; Published: May 15, 2024

Copyright: © 2024 Cameron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This study was self-funded by Lily Cameron, as part of her dissertation of the Master’s in Humanitarian Studies programme at the Liverpool School of Tropical Medicine. MMC and NvD did not receive any funding for this work. Co-author HMC was funded by a grant from the Global Fund (20168770). The funders played no role in the writing of the manuscript or the decision to submit it for publication. Publication costs were supported by Ken Newell Bursary from the Liverpool School of Tropical Medicine.

Competing interests: The authors have declared that no competing interests exist.

List of abbreviations: ALNAP, Active Learning Network for Accountability and Performance; CAPS-1, Clinician Administered PTSD Scale; CCAT, Crowe Critical Appraisal Tool; EE, Emotional Exhaustion; DP, Depersonalisation; ERI, Effort-Reward Imbalance; GHQ-28, General Health Questionnaire; HSCL-25, Hopkins Symptom Checklist; HTQ, Harvard Trauma Questionnaire; IASC, Inter-Agency Standing Committee; IES-R, Impact of Event Scale; JCQ, Job Content Questionnaire; LMIC, Low- and middle-income country; MeSH, Medical Subject Heading; MBI-HSS, Maslach Burnout Inventory-Human Services Survey; NGO, Non-governmental organization; PA, Personal Achievement; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; ProQuol, Professional Quality of Life; PTSD, Post-Traumatic Stress Disorder; PCL-5, PTSD Checklist; RWBQ, Relief Worker Burnout Questionnaire; STSS, Secondary Traumatic Stress Scale; UNOCHA, United Nations Office for the Coordination of Humanitarian Affairs

Humanitarian crises and disasters world-wide has risen dramatically in recent years [ 1 ]. In 2022, it was estimated that 274 million people needed humanitarian assistance and protection to meet human physical, psychological and social needs and to relieve suffering [ 2 , 3 ]. The physical, psychological and social needs resulting from humanitarian crises often exceed available resources and overwhelm local capacity in the country affected [ 4 ]. Increasingly, affected populations rely upon the global community to offer assistance in disaster related challenges [ 5 ].

Humanitarian aid workers use their time and skills to respond to the human costs of disasters working with non-governmental organisations (NGOs) [ 6 , 7 ]. Humanitarian aid workers can be local, national or international. They offer varied skills and experience, ranging from logistical support such as drivers, to highly skilled medical healthcare providers [ 7 ]. In the 2018 State of the Humanitarian System study, it was estimated that 570,000 individuals were employed by humanitarian agencies across different country settings [ 8 ]. Each humanitarian disaster is context specific and therefore the activities of a humanitarian aid worker can vary but generally encompasses the protection of civilians, as well as the delivery of food, water, healthcare and shelter, coordination and management of activities [ 3 ]. Working in hostile environments, such as in the aftermath of a natural disaster or ongoing conflict, is extremely challenging and dangerous [ 9 ]. It is well recognised that humanitarian aid workers can experience physical threats including exposure to gunfire, shelling and bombing, injury by landmines and road traffic accidents [ 10 ]; and exposure to traumatic events is a stressful occurrence. Other challenges described include physically demanding working conditions; excessive workload, chronic fatigue; lack of adequate resources and logistical support; interpersonal conflict among team members; and navigating moral and/or ethical dilemmas [ 11 ]. It is well recognised that exposure to stressors (acute and chronic) negatively affect humanitarian aid workers’ mental health and can lead to short and/or long term adverse mental health [ 5 , 10 , 12 – 18 ]. Individual studies have described that different types of humanitarian aid workers are at increased risk of developing depression [ 12 , 13 , 15 , 19 ], anxiety [ 12 , 13 , 15 , 19 ], burnout [ 12 , 13 , 15 ] and post-traumatic stress disorder (PTSD) [ 12 – 14 , 19 ], in addition to hazardous alcohol consumption as a coping mechanism [ 19 , 20 ].

In addition to the adverse effects on mental health for people working in humanitarian settings, research has demonstrated that distress in humanitarian workers can negatively impact work efficiency and efficacy and can lead to poor-decision making in the field [ 21 ]. There are also growing concerns regarding attrition rates of staff from NGOs leading to excess expenditure for organizations, as they must recruit, train and deploy new staff [ 8 ]. The main focus in humanitarian settings is often on physical safety and security but organizations are becoming more aware that there is a need to put mental health support in place and to understand what the key risk factors for mental ill-health among their staff are [ 1 , 10 ].

We conducted a systematic review and meta-analysis 1) to assess the occurrence of mental ill-health among humanitarian aid workers and 2) to explore reported factors associated with mental ill-health in humanitarian aid workers.

Material and methods

CINAHL plus, Cochrane library, Global Health, Medline, PubMed and Web of Science databases were searched. Google Scholar was used to search grey literature. Broad keywords were developed and used to generate a sensitive yet specific advanced search using humanitarian aid worker and burnout, anxiety, depression and PTSD. A preliminary search showed that these mental ill health conditions were the most reported in the literature. Medical Subject Heading (MeSH) terms were added to increase the number of results and widen the scope of the search ( Table 1 ). The search included studies conducted worldwide, in all languages published between 2005 and 2020. This timeline was used due to the formation of the Cluster Approach in 2005 [ 22 ]. Searches were carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [ 23 ]. In addition to database searching, manual reference and key author publication searching were carried out.

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Inclusion and exclusion criteria

All studies which reported occurrence of mental ill-health assessed in humanitarian aid workers were included. Studies reporting only historical or biographical narratives or individual case studies were excluded. Studies investigating outcomes in civilian victims of humanitarian crisis or non-humanitarian aid workers (for example military personnel) were also excluded.

Screening, selection and data extraction

Two researchers independently screened all titles and abstracts. Evaluation of full-text studies was done independently by two researchers with reasons for exclusion recorded and any discrepancies were discussed with a third researcher. There was good agreement and similar ratings between the researchers regarding inclusion or exclusion of papers and only four papers required a third researcher review and opinion to reach consensus. Information was extracted into a pre-designed summary table and included description of the study and setting and data on the screening and/or diagnostic tools used. Additionally, data on the occurrence of the following were extracted: psychological distress, burnout, anxiety, depression and PTSD as described and reported by the authors. Throughout the reviewing and extraction processes, studies where uncertainty existed were discussed by all researchers to reach a consensus.

Quality assessment

The Crowe Critical Appraisal Tool (CCAT) version 1.4 was used to perform quality appraisal of the studies eligible for inclusion. The CCAT was developed to overcome recognised limitations of existing critical appraisal tools (CATs) [ 24 ]. For example, most CATs appraise either one or a small number of research designs, as well as lacking the depth needed to rigorously appraise research [ 24 ]. The developers of the CCAT also recognised that a limited number of CATs have readily available validity and reliability data [ 24 ]. The CCAT was designed to be used in all research designs in health [ 25 ]. The CCAT consists of eight categories, which are further divided into 22 items and 98 item descriptors [ 24 ]. Studies are given a score for each category and scores are combined to give an overall score [ 24 ]. Each study was appraised using the CCAT Form and the CCAT User Guide together as advised by the authors, in order to ensure the most accurate scoring possible.

Ethics approval and consent to participate

This systematic review did not involve contact with any human participants, and therefore ethical approval was not required. This study was conducted in compliance with the established ethical guidelines of the Declaration of Helsinki.

Data synthesis

Narrative synthesis was used to summarise the findings including for associated risk factors identified and as reported in the studies. The key findings of the studies were collated into a textual narrative, and differences between the characteristics of each study were compared [ 26 ]. To conduct a meta-analysis for each of the five outcomes reported (psychological distress, burnout, anxiety, depression and PTSD) a random effects logistic regression model was applied to the data using Stata version 14.2 to estimate the underlying odds (with 95% confidence interval) of the outcome, with study as the only (random) term use in the model [ 27 ]. The estimated odds of failure and the variance of the random effects are both reported on the odds scale; additionally, the odds are reported on the natural probability scale.

The database search yielded 1309 results and a further 12 papers were identified through reference and author searching. After exporting all the references to EndNote X9, duplicates were removed to leave 1122 records. The remaining articles were screened, first by title and then by abstract, using application of the inclusion and exclusion criteria. Of these articles, 1087 did not meet the inclusion criteria, meaning that the majority were excluded. The full texts of the 35 articles not excluded by abstract screening were downloaded. Google Translate was used to translate two articles that were not published in English [ 28 , 29 ]. The inclusion and exclusion were applied to the full-text articles. After review 26 full text papers were excluded and nine papers were established as eligible for inclusion in the review ( Fig 1 – PRISMA flow diagram. Mental ill-health amongst humanitarian aid workers: Study Selection for Review). Of the nine papers included most papers were assessed to be of high quality with a score of 70%–93% obtained. One paper received a score of 63% as consideration of ethical matters was not reported ( Table 2 ).

Mental ill-health amongst humanitarian aid workers: Study Selection for Review.

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Study population

Five studies surveyed international humanitarian aid workers only [ 28 , 30 – 33 ] and four studies assessed both national and international aid workers [ 19 – 21 , 34 ]. The most common term used to describe the participants was ‘humanitarian aid worker’. Other terms included: ‘relief force worker’, ‘aid worker’ and ‘humanitarian worker’. Six studies provided details of the job roles of the humanitarian aid workers who participated [ 19 , 20 , 28 , 30 , 31 , 33 ]. The most featured professionals were managerial or coordination staff [ 19 , 20 , 31 , 33 ]. Two studies included healthcare providers such as doctors, nurses, physiotherapists and psychologists [ 28 , 30 ]. Other job areas included were logistics [ 20 , 30 , 31 ], technical [ 19 , 20 , 28 , 31 ], administration [ 19 , 31 ], maintenance [ 28 ]. A total of 3,619 humanitarian workers were assessed across the nine included studies of which 1,774 were international humanitarian aid workers. This provided a total of 6,124 assessments for inclusion in the meta-analysis ( Table 2 ).

Geographical location

Five studies included details of the country of origin of its participants [ 20 , 21 , 28 , 30 , 33 ]. Many of the studies involved individuals from several countries. High income countries were the most represented, with most of the participants originating from the United States of America (USA) and Western Europe. Five studies included information regarding the destination countries of the participants including: Indonesia [ 30 ]; Albania [ 20 ]; Haiti [ 28 ]; Sudan [ 34 ]; and South Sudan [ 19 ]. In three of these studies, the participants were working in a war or conflict setting; the conflicts in Sudan [ 34 ], South Sudan [ 19 ] and Kosovo [ 20 ]. In the other two studies, the setting was the aftermath of a natural disaster; the 2010 Haiti earthquake [ 28 ], and the 2004 Indian Ocean tsunami [ 30 ].

Study design and data collection methods

Eight studies were cross-sectional [ 19 – 21 , 28 , 30 , 32 – 34 ], and one study was a cohort longitudinal study. Seven studies collected data via a survey or questionnaire [ 19 – 21 , 28 , 31 , 32 , 34 ]. In two studies the survey was accessed via email and completed online [ 21 , 32 ]. Two studies used survey interviews to collect data face-to-face [ 30 , 33 ].

Different types of screening or diagnostic tools were used to assess mental health status in the included studies ( Table 3 ) The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was most used to assess burnout, appearing in four studies [ 19 , 21 , 31 , 33 ]. The MBI-HSS uses three subscales; emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA), to calculate burnout risk [ 35 ]. The cut-off scores for identifying high risk for burnout are: EE >27; DP >13; and PA <31 [ 35 ]. The Relief Worker Burnout Questionnaire, which uses the participant’s score to indicate the likelihood of burnout [ 36 ], was used in one study [ 34 ]. In this questionnaire, a score of 16–25 suggests suffering from work stress, 26–35 suggests possible burnout and >35 indicates probable burnout. The General Health Questionnaire (GHQ-28) and the Hopkins Symptom Checklist (HSCL-25) were used to screen for anxiety, depression and psychological distress in five studies [ 19 , 20 , 31 , 32 , 34 ]. The GHQ-28 measures emotional distress using four subscales to determine ‘psychiatric caseness’ [ 37 , 38 ]. When using the binary scoring method, any score exceeding 4/28 is classified as achieving ‘psychiatric caseness’.

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The HSCL-25 is a commonly used screening tool for anxiety and depression, in which the score is used to indicate anxiety or depression caseness [ 39 ]. A score of 1.75 or more in each of the anxiety or depression subsections indicates caseness. Five studies investigated PTSD using the following tools: the Clinician-Administered PTSD Scale (CAPS-1) [ 30 ], the Harvard Trauma Questionnaire (HTQ) [ 20 ], the Impact of Event Scale (IES-R) [ 28 ], the Professional Quality of Life (ProQol) scale [ 34 ], and the PTSD Checklist for DSM (PCL-5) [ 19 ]. The Audit-C test to assess for hazardous drinking was used in one study [ 19 ]. All data collection tools have been validated in different settings [ 40 – 47 ] ( Table 3 ).

Occurrence of mental ill-health

Two papers reported on psychological distress [ 24 , 25 ]. One longitudinal study reported 6.5% occurrence of psychological distress before deployment and up to 17.7% following deployment among a range of staff including managers, coordinators, technical and logistics staff [ 24 , 25 ]. One study used two models to assess psychological distress including the Job Demand-Control-Support (JDC-S) and Effort-Reward Imbalance (ERI) models with more than half of the participants sampled (52.8%) reporting psychological distress, and one third reporting high ERI and high job strain [ 25 ]. This study reported that two models used in combination offered a superior estimation of the likelihood of psychological distress than one model alone [ 25 ]. An increased risk of burnout was described in five studies with a range of occurrence between 8.5% and 32% reported [ 19 , 21 , 31 , 33 , 34 ]. The highest occurrence was reported in a study including 1,980 international and local humanitarian aid workers of an international organization that operates in more than 100 locations worldwide [ 16 ]. Three studies reported on anxiety [ 19 , 20 , 31 ] which ranged from an occurrence of 3.8% pre-deployment [ 24 ] and 7.8% to 38.5% [ 13 ] during and after deployment. The same three studies also assessed depression [ 19 , 20 , 31 ] with an assessed occurrence of 10.4% pre-deployment [ 24 ] and 17.1% to [ 15 ] 39% during and after deployment [ 19 , 20 ].

PTSD was assessed in five of the included studies [ 13 , 15 , 21 , 23 , 27 ]. Results ranged from no occurrence [ 21 ] to 25.0% [ 27 ]. One study used the Impact of Event Scale—Revised (IES-R) to screen for symptoms of PTSD with no occurrence detected amongst 66 humanitarian aid workers following an earthquake in 2010 [ 28 ]. Three studies [ 13 , 23 , 27 ] provided similar levels of occurrences with 1 in 4 participants screening positive for PTSD. Hazardous drinking was measured as a negative mental health outcome in two studies [ 19 , 20 ]. One study reported that 46 of 284 (16.2%) of international aid workers reported drinking alcohol at hazardous levels [ 20 ] and another study reported that 50% of male and 41% of female international aid workers reporting drinking levels suggestive of disorder [ 19 ].

Meta-analysis

Between two and five studies reported on each of the five types of mental ill-health identified ( Table 2 ). Among humanitarian aid workers the odds ratio (OR) (95% CI) for psychological distress was 0.45 (0.12–1.64); burnout 0.34 (0.27–0.44); anxiety 0.22 (0.10–0.51); depression 0.32 (0.18–0.57) and PTSD 0.11 (0.03–0.39) ( Table 2 ).

Factors associated with mental ill-health

Exposure to traumatic events was reported as being associated with an increase of mental ill-health in four studies [ 19 , 20 , 30 , 31 ] ( Table 4 ). A significant association between exposure and negative mental health outcomes was found in three of the studies, with higher levels of hazardous alcohol consumption, depression and PTSD found in those with higher levels and/or frequency of trauma exposure [ 19 , 20 , 31 ]. Poor living conditions, security concerns, heavy workload, poor social support networks and lack of communication were identified as important ‘stressors’ and were found to impact the mental health of international humanitarian aid workers [ 24 ]. Three studies measured stress exposure, with increased risk of psychological distress, anxiety, depression and PTSD reported in humanitarian aid workers with higher chronic stress levels [ 19 , 21 , 31 ]. Three studies provided information regarding the pre-deployment mental health, or pre-existing mental health conditions, with a range of 9.4–19.3% of humanitarian workers self-reporting a history of mental illness [ 19 , 20 , 31 ]. Two found a significant association between a pre-existing psychiatric history and negative mental health outcomes post-deployment [ 20 ]. A history of mental illness was found to be positively associated with depression and non-specific psychiatric morbidity, and negatively associated with anxiety [ 20 , 31 ]. Younger compared to older humanitarian aid workers were reported to be more at risk of developing mental ill-health, including depression and burnout [ 20 , 21 , 33 ]. Four studies investigated gender as a factor [ 19 , 21 , 30 , 34 ], with female humanitarian aid workers more at risk of PTSD, burnout and anxiety than male humanitarian aid workers [ 19 , 21 , 30 , 34 ]. However, male humanitarian aid workers were more likely to report hazardous alcohol consumption [ 19 , 20 ]. Only three studies reported on support mechanisms and one study referenced pre-deployment training or post-deployment debrief [ 20 , 31 , 33 ]. International humanitarian aid workers who received high levels of support from their organisation reported lower rates of depression and burnout [ 20 , 33 ] ( Table 4 ).

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Key findings

Humanitarian aid workers experience negative mental ill-health (psychological distress, burnout, anxiety, depression and PTSD) as a result of their experiences providing relief to vulnerable populations as part of humanitarian aid work. Associated factors for mental ill-health include exposure to traumatic events, younger age, and being female. More men reported drinking alcohol at a hazardous level. Support from organisations resulted in lower rates of burnout and depression.

Strengths and limitations

To our knowledge, this is the first systematic review and meta-analysis to focus on mental ill-health outcomes in humanitarian aid workers. The searches were not limited by geographical location or language, further increasing the chances for all relevant literature to be identified. However, it was not possible to approach researchers directly who were working in regions affected by major conflict and human displacement for any unpublished data. The search was conducted for paper published from 2005 and 2020. This timeline was used because in 2005 the Emergency Relief Coordinator and the Inter-Agency Steering Committee (IASC) initiated the reform of the humanitarian system, resulting in the formation of the Cluster Approach [ 22 ]. Although all the screening tools used are validated, the variety of screening tools used across the included studies must be considered when interpreting the results of this review. We acknowledge that this is a limitation and highlight the need for standardisation of assessment tools and international agreement on cut-off points while appreciating that this is the real-life pragmatic approach currently taken by organisations as well as researchers. Furthermore, all but two of the data collection tools were self-reported questionnaires, with no clinical follow-up to confirm diagnoses.

Interpretation of findings

Although many of the included studies followed the same trends, there was variation in the rates of mental ill-health reported. In addition to variation in screening tools as well as timing of screening, a further explanation for this could be the country of origin of the humanitarian aid workers. Cultural differences have been shown to have implications for mental ill-health, including how mental illness is viewed, if and how it is reported and how treatment is accessed [ 48 ]. Although not all the included studies gave information regarding the nationalities of their participants, most of the humanitarian aid workers sampled were from high-income countries. One explanation for the high rates of burnout in international workers maybe that international aid workers work in an unfamiliar setting. This paired with the unrealistic expectations of humanitarian aid work, can lead to emotional exhaustion and burnout [ 21 ]. National workers, by comparison, can often relate to the victims of disaster and may even have been affected by humanitarian crisis themselves. Therefore, providing humanitarian aid could lead to further trauma for national workers, which could explain why they are more at risk of PTSD and other mental ill-health outcomes such as anxiety [ 7 ]. Different settings of deployment, such as natural disasters or conflict zones, present different challenges for the delivery of aid, which could lead to different mental health impacts for affected humanitarian aid workers. It has been suggested that people tend to be more frustrated about disasters that are caused by humans, such as armed conflict [ 49 ]. Some research has shown that the psychological impacts of man-made disasters can be more pronounced than those of natural disasters such as earthquakes or floods [ 50 ].

Pre-existing mental ill-health have been shown to be a risk factor for the development of new psychological morbidity following disasters [ 51 ]. Therefore, it was surprising that only three of the included studies collected data on previous mental ill-health of their participants. An explanation for the positive association between younger age and increased negative mental ill-health could be that older humanitarian aid workers have developed more effective coping strategies through their life experiences [ 21 ]. However, it could be that the older individuals sampled are those that have chosen to stay in the humanitarian sector [ 33 ]. Others may have in fact experienced negative mental ill-health, and not returned to humanitarian work as a result. Findings regarding the significance of gender as a risk factor were inconsistent in this review. Research has shown that gender has a role to play for mental ill-health, so although overall rates of psychiatric disorders are almost the same in men and women, there are big differences in the patterns of mental illness between the genders [ 52 ]. For example, female humanitarian aid workers can be more exposed to risk factors for negative mental ill-health, such as sexual harassment and gender-based violence [ 19 ].

The benefits of adequate training for humanitarian aid workers are well documented. Pre-deployment training can prepare individuals for the challenges they may face while working in a disaster setting and can help to build resilience [ 53 ]. Team building exercises have also been shown to be useful in strengthening communication, which can be protective against organisational stressors [ 18 ].

The literature regarding post-deployment debriefing was more inconclusive. Debriefing is thought to reduce the impact of trauma by allowing an individual to reconstruct their experiences [ 5 ], and it has been shown to reduce distress and anxiety [ 17 ]. However, there is some evidence that debriefing is in fact unhelpful, and that focusing on the traumatic incident should not be routine practice [ 45 ]. With this evidence in mind, both the Inter-Agency Standing Committee (IASC) and the Antares Foundation have developed guidelines outlining key actions for organisations to address the psychological needs of the humanitarian aid workers they employ [ 54 , 55 ].

Implications of findings

Mental ill-health has a significant negative impact on an individual’s personal well-being, and on a larger scale can reduce the efficacy of humanitarian organisations with delivery of aid and retainment of staff. A pre-existing mental health condition is a risk factor for the development of further psychological problems in humanitarian aid workers, and it is essential that appropriate screening is conducted prior to deployment. Individuals who are more at risk should be provided with extra support and follow up management. Education should be provided to all prospective humanitarian aid workers regarding the potential negative psychological impacts of working in a humanitarian setting. Pre-deployment training can greatly improve the resilience and overall preparation of humanitarian aid workers [ 5 , 17 , 18 , 53 ] and it is important that humanitarian organisations follow all available guidelines and provide adequate pre-deployment training for of all their employees. Psychological support systems need to be in place for humanitarian aid workers both during and after deployment. Care needs to be taken to reduce the workload of individual workers where possible, in order to reduce stress and subsequent stress-related mental illness. Although the evidence surrounding formal debriefing is inconclusive, support in the form of confidential counselling should be readily available to humanitarian workers at all points following deployment.

Humanitarian aid workers are exposed to a range of stressors and traumatic events whilst providing aid in humanitarian emergencies, and this can result in the exacerbation of pre-existing mental ill-health and/or the development of new mental ill-health including psychological distress, burnout, anxiety, depression, and PSTD. It is imperative that mental ill-health is screened for, detected and treated for humanitarian aid workers, before, during and after their deployment. Humanitarian organisations must be responsible to prevent and manage mental ill-health by providing support (for example freely available, confidential counselling) prior to, during and post-placement. The use and need for humanitarian assistance are ever increasing and it is important that humanitarian aid workers are healthy and able to function to the highest standard. Although there appears to have been an increase in attention on the mental health of humanitarian aid workers in recent years, there is still a need to conduct further large-scale research to investigate the associations between humanitarian work and mental ill-health. Further research needs to investigate the most effective training and support systems that need to be in place for humanitarian aid workers.

Supporting information

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https://doi.org/10.1371/journal.pone.0292107.s001

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• Systematic Review
• Open access
• Published: 20 May 2024

Smokeless tobacco consumption among women of reproductive age: a systematic review and meta-analysis

• Ramaiah Itumalla 1   na1 ,
• Mahalaqua Nazli Khatib 2   na1 ,
• Shilpa Gaidhane 3 ,
• Quazi Syed Zahiruddin 4 ,
• Abhay M Gaidhane 5 ,
• Ahmad Neyazi 6 , 7 ,
• Ahmad Farshid Hassam 6 ,
• Prakasini Satapathy 8 , 9 ,
• Sarvesh Rustagi 10 ,
• Neelima Kukreti 11 &
• Bijaya Kumar Padhi 12  

BMC Public Health volume  24 , Article number:  1361 ( 2024 ) Cite this article

Metrics details

Smokeless tobacco (SLT) poses many negative health impacts. Despite its longstanding presence in societies across the world, the health implications of SLT have only been rigorously studied in recent decades. This systematic review and meta-analysis aimed to consolidate existing research to provide a comprehensive understanding of the global prevalence of SLT use among women of reproductive age. Relevant articles were extracted from databases such as PubMed, EMBASE, Web of Science, and Scopus from their inception until November 11, 2023. Observational studies reporting the number of SLT users among women of reproductive age were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) tool. The meta-analysis used a random-effects model to determine SLT prevalence, supported by statistical tools like forest plots, I 2 statistics, and sensitivity analyses to ensure the accuracy and comprehensiveness of the results. All statistical analyses were performed in R version 4.3. From 10 studies involving 2,053,667 participants, a pooled prevalence for SLT use among women of reproductive age was found to be 9.3% (95% CI: 0.038 to 0.21), with significant heterogeneity among studies (I 2  = 100%). Publication bias was suspected among the studies. Sensitivity analysis and subgroup analysis couldn’t resolve the heterogeneity. Our analysis shows a significant prevalence of SLT use in women of reproductive age, especially in low socioeconomic and developing countries like India, Pakistan, and Nepal. For women of reproductive age, the use of smokeless tobacco (SLT) can lead to infertility, pregnancy complications, and adverse fetal outcomes, including low birth weight and preterm birth. The results highlight the necessity for specific public health measures and policy changes to decrease SLT consumption among reproductive-age women. Further studies are needed to investigate the reasons behind SLT usage in this group and to assess the impact of intervention strategies, to guide more effective public health initiatives and policies.

Peer Review reports

Introduction

Tobacco consumption represents a major health concern due to its strong association with a range of chronic diseases [ 1 ]. Over two-thirds of fatalities in developing nations are attributed to non-communicable diseases (NCDs), and tobacco use is a major preventable contributor to these deaths [ 2 ]. Despite numerous international policy initiatives, aimed at reducing tobacco consumption, such as the Framework Convention on Tobacco Control (FCTC) by the World Health Organization, the trend in tobacco use continues unabated [ 3 ]. By 2030, it has been estimated that tobacco use will result in ten million premature deaths per year [ 4 ]. Developing countries are disproportionately affected, contributing to nearly 70% of tobacco consumption and associated deaths [ 4 , 5 ].

Tobacco products are categorized into smoking types, including cigarettes, cigars, and pipes, and smokeless forms, such as snus, chewing tobacco, and dissolvable tobacco, each contributing to the health epidemic [ 6 , 7 , 8 , 9 , 10 , 11 ]. Globally, smokeless tobacco (SLT) is consumed in various forms, such as chewing tobacco, snuff, and snus [ 12 ]. Historically, the use of SLT has deep roots in many cultures, often seen as a part of social rituals and traditional practices [ 13 ]. Despite the longstanding presence of SLT in societies across the world, its health implications have only been rigorously studied in recent decades. SLT is often misleadingly perceived as a safer alternative to smoked tobacco, which may also has contributed to its widespread use [ 14 , 15 , 16 ]. This misconception is particularly prevalent in regions like South Asia, parts of Europe, and North America. The cultural acceptance and traditional use of SLT in these regions complicate efforts to mitigate its health risks [ 17 , 18 ]. Understanding the complexities of SLT consumption, its cultural ties, and perceived risks is crucial for comprehensive research, especially when focusing on specific demographics such as women of reproductive age [ 18 ].

Over 30 carcinogens were contained in SLT and those strongly associated with multiple types of cancers, including oral, oropharyngeal, oesophageal, and pancreatic cancer [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. It also significantly contributes to cardiovascular diseases and hypertension [ 26 ]. The systemic impact of SLT extends beyond these direct health risks. It affects oral hygiene, leading to dental issues, and contributes to increased susceptibility to infections [ 27 ]. For women of reproductive age, the use of SLT introduces additional concerns, such as infertility [ 28 ], complications during pregnancy, and adverse fetal outcomes, like low birth weight and preterm birth [ 29 ].

The prevalence of SLT use among women of reproductive age (15 to 49 years) is a critical public health issue. Women in this demographic are particularly vulnerable due to potential adverse effects on both themselves and their offspring. In some cultures, SLT use among women is a taboo, leading to underreporting and lack of visibility in public health discourses. In others, SLT is used as a traditional remedy for ailments like toothache and nausea during pregnancy, exacerbating its use among women of reproductive age [ 30 , 31 , 32 ].

Several systematic reviews have focused on different aspects of SLT, covering its adverse outcomes and risk factors [ 12 , 33 , 34 , 35 , 36 ]. Women of reproductive age represent a crucial demographic due to their potential impact on both maternal and child health. SLT use in this group can have significant adverse outcomes, including impacts on pregnancy outcomes, fetal development, and increased risk of developing non-communicable diseases. Understanding the prevalence of SLT use among these women is vital for targeted public health interventions and policies. While individual primary studies have been published on the prevalence of SLT use among women of reproductive age, to date, no systematic review has assessed the overall prevalence of SLT in this specific population [ 33 , 34 , 35 , 36 ]. This review aims to guide public health strategies, inform policies, and spur further research to decrease smokeless tobacco use among reproductive-aged women, aligning with the sustainable development goals (SDG-3) to ensure healthy lives and promote well-being for all ages, thereby enhancing maternal and child health outcomes.

This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 37 ] (Table S1 ). A protocol has been prospectively registered in the PROSPERO: CRD42023482095.

Selection criteria

Original research conducted among women of reproductive age 15 to 49, published in peer-reviewed journals was considered for inclusion. Observational studies like surveys, cross-sectional studies, and longitudinal studies were included. Studies which reported the proportion of women consumed SLT were included. Studies that reported SLT use among the general population or men were excluded. Reviews, case reports, case series, non-human studies were also excluded. Articles available in the English language were considered (Table S2 ).

Literature search and screening

A literature search was conducted among databases like PubMed, EMBASE, Web of Science, and Scopus since inception to November 11, 2023. Keywords and MeSH terms related to SLT, reproductive women were used to search. No restrictions were placed on the search regarding the type of article, year of publication, or language (refer Table S3 ).

The screening process was performed in two steps: title and abstract screening followed by full-text screening. A semi-automated software (Nested Knowledge, USA) was used for de-duplication and screening. Two reviewers (RI and MNK) performed screening independently. A third reviewer (BKP) was consulted to resolve discrepancies regarding the inclusion of articles.

Data extraction

Data extraction was performed by two reviewers (RI and MNK), followed by a double-check conducted by a third reviewer (QSZ) to ensure accuracy and consistency. For each included article, the data extracted included the author’s name, year of publication, study design, country, age of participants, sample size, and the number of SLT users. This comprehensive approach allowed for a detailed analysis of the studies’ key characteristics and demographic information, providing a robust foundation for the systematic review.

To assess the quality of each included study, a meticulous quality assessment was performed using the Joanna Briggs Institute (JBI) tool for prevalence studies [ 38 ]. The JBI assessment tool for prevalence studies covers various aspects, including the representativeness of the sample, the appropriateness of the study’s methodology, the validity and reliability of the measures used, and the adequacy of response rates.

Statistical analysis

A meta-analysis was conducted to determine the prevalence of SLT use among women of reproductive age, using a random-effects model to pool the number of SLT users and the total sample size of women in this age group. A forest plot was generated for visualization, and the I 2 statistic was employed to assess study heterogeneity, indicating the percentage of variation due to heterogeneity rather than chance, with values ranging from 0 to 100% [ 39 ]. The analysis also included a 95% prediction interval and the tau-squared value for a deeper understanding of between-study variance [ 40 , 41 ]. Subgroup analysis based on country and a leave-one-out sensitivity analysis were performed to gauge the influence of individual studies on overall results. Doi plot with LFK index was used to determine publication bias [ 42 , 43 ]. Significance level was set at a p-value below 0.05, and all statistical analyses were conducted using R software, version 4.3 [ 44 ].

Literature search

A total of 310 records were identified from multiple databases. Of these, 68 were duplicates. A total of 87 articles were subjected to screening, of which 41 were excluded. Subsequently, 46 articles were assessed for eligibility. Out of these, 9 articles were found eligible. Additionally, 2 articles were identified from a citation search, among which 1 article was found to be eligible. Finally, a total of 10 studies were included in this review. Figure  1 depicts the process of screening and selection of studies.

PRISMA flow diagram showing the screening and selection process

Characteristics of included studies

Table  1 presents a summary of the features of the studies that were included. Out of the 10 studies, one was retrospective in design, while the rest were cross-sectional. The majority of these What studies were conducted in Southeast Asian regions ( n  = 7), specifically in countries like India ( n  = 5), Pakistan ( n  = 1), and Nepal ( n  = 1), reflecting a geographical focus on this area. One study included data from multiple countries. One study was available from Sweden. The age range of participants varied from 15 to 49 years, covering a wide spectrum of the female reproductive age group. The quality of the studies was found to be moderate to high, as assessed by the JBI tool (referenced in Table S4 ).

• Meta-analysis

From 10 studies involving 2,053,667 participants, a pooled prevalence for SLT use among women of reproductive age was found to be 9.3% (95% CI: 0.038 to 0.21), with significant heterogeneity among studies (I 2  = 100%). A prediction interval of 0.004 to 0.73 was observed. Figure  2 illustrates the forest plot. This indicates that, on average, about 9.3% of women of reproductive age in the studied populations use SLT. This high level of variability indicates that the prevalence rates of SLT use among women of reproductive age may vary widely across different studies and populations. The wide prediction interval ranging from 0.4 to 73% suggests that in a similar future study, the prevalence of SLT use among women of reproductive age could fall anywhere within this wide range. This reflects the significant variation in SLT use prevalence that could be expected across different settings and populations.

Forest plot depecting the pooled prevalence of SLT use among women of reproductive age

The subgroup analysis based on country revealed that 5 studies from India [ 45 , 46 , 47 , 48 , 49 ] with 807,167 participants showed a prevalence of 14% (95% CI: 0.048 to 0.35) with I 2  = 100%. Two studies from Pakistan [ 50 , 51 ] revealed a similar prevalence of 10% (95% CI: 0.00 to 1.00). Nepal showed a prevalence of 13% (95% CI: 0.12 to 0.15) involving 1,902 participants from a single study [ 52 ]. In the study which included multiple countries [ 53 ], the prevalence was found to be 0.9% (95% CI: 0.008 to 0.009), involving 1,230,262 participants (Fig.  3 ).

Leave one out analysis of pooled prevalence

Sensitivity analysis and publication bias

We performed a sensitivity analysis by leaving one study out at a time. No significant change was observed in the overall analysis. Omitting the study by Mohandas et al. reduced the prevalence to 7.4%. Similarly, omitting Shukla et al. increased the prevalence to 12% (Fig.  4 ). In assessing the potential for publication bias within our systematic review, we utilized a Doi plot accompanied by the LFK index. The Doi plot revealed an evident asymmetry in the distribution of the effect sizes, which were plotted against their respective z-scores. The majority of studies clustered to one side of the effect size spectrum, which is a visual indicator of potential publication bias. This visual indication was quantitatively supported by an LFK index of 4.23, significantly surpassing the threshold of 1, which is typically used to denote substantial asymmetry. This high LFK index suggests that our meta-analysis may be influenced by publication bias, where studies with non-significant or negative results could be underrepresented in the literature. The implications of this are critical; the effect sizes reported in our review should be interpreted with caution, as the true effects could be overestimated due to the preferential publication of studies with positive results (Fig.  5 ).

Subgroup analysis of SLT use among women of reproductive age based on country

Doi plot illustrating the publication bias

To our knowledge, this study is the first systematic review and meta-analysis to assess the prevalence of SLT use among women of reproductive age. Our findings indicate a considerable prevalence of SLT use in this demographic, which has significant public health implications. The pooled prevalence of 9% necessitate the need for targeted interventions and policy reforms, especially in regions with higher usage rates.

The nature of included studies varied in our review. The study by Rolandsson et al. [ 54 ] is the only analysis conducted in a developed country, Sweden, focusing on female athletes. It revealed that a vast majority of the participants had never smoked or used snuff, highlighting the healthy behaviors of this population. However, a notable number had experimented with snus (20%) or smoking (27%), though the regular use of snus was comparatively low against other countries reviewed. This may reflect better awareness of tobacco’s negative impacts and heightened health consciousness in Sweden. The study also found significant correlations between the smoking behaviors of female athletes and those of their mothers and peers. Another study by Khan et al. presents significant insights into the use of alternative tobacco products, such as chewing tobacco (CT), among women of reproductive age in Pakistan [ 51 ]. The prevalence of these alternative tobacco forms aligns with the most recent national data reported by the World Health Organization. Notably, there’s a higher usage rate among vulnerable groups of Pakistani women in their reproductive years. Several factors must be considered when analyzing this prevalence. While the overall tobacco use among women is less than that of men, factors such as aggressive marketing, the rising popularity of alternative tobacco forms like waterpipe, and changing societal attitudes towards women can increase their susceptibility to tobacco-related risks. The study also highlights that women with a lower socio-economic status (no education or poor) are more prone to using alternative tobacco forms. This trend is particularly evident among the poor, uneducated, rural inhabitants, and those who have not accessed health facilities in the last year, indicating a higher propensity for health risk behaviors like CT use [ 51 ]. Mishra and colleagues discovered a significant link between the use of tobacco products, including smoking and smokeless forms, as well as alcohol consumption, and an increased incidence of Non-Communicable Diseases (NCDs) in women [ 46 ].

Similar findings highlighting the issue of SLT were also reported in other studies. Particularly, a known risk factor for oral cancers, contributing to morbidity in Indian women, especially those from lower socioeconomic backgrounds [ 55 , 56 , 57 , 58 ]. The combined effects of tobacco and alcohol use were found to significantly elevate the prevalence of NCDs in women. This study underscores the substantial population-attributable risk posed by smoking, using SLT, and alcohol consumption for NCDs among women. These findings align with previous research from India and other developing countries, indicating a heightened risk of hypertension and other NCDs due to smoking and alcohol use. Consequently, these results underscore the urgent need to develop effective prevention strategies to counter the rising trend of NCDs by addressing tobacco and alcohol consumption. Similarly, Muhammad et al. proposed that gutka (chewable SLT mixture consisting of betel nut and catechu) use is a significant predictor of anemia, a finding that might hold true for other coastal slums as well [ 50 ]. The study posits that gutka’s components could interfere with intestinal iron absorption and disrupt various biological processes. Notably, chewable tobacco, a key ingredient in gutka, contains iron that impacts iron metabolism, hemoglobin levels, and iron stores. This could potentially influence or diminish the expression of hepcidin mRNA and lower hepcidin levels, which are essential for maintaining iron balance, especially in pregnant women [ 59 , 60 , 61 , 62 ]. Furthermore, the crushed areca nut in gutka, which includes alkaloids, may impair the intestine’s ability to absorb iron. Additionally, calcium hydroxide, commonly found in gutka, is known to inhibit iron absorption [ 63 ]. Studies suggests that the observed link between gutka use and anemia might be due to these mechanisms [ 50 , 64 , 65 , 66 ]. Its effect is profound even in non-pregnant women. SLT can lead to impairments in ovarian function, morphology, oocyte quality, and hormonal regulation [ 28 ].

The implication of our findings are profound. Effective public health interventions need to be targeted at regions with higher SLT usage. These interventions should focus on education about the risks associated with SLT. Addressing socioeconomic disparities is crucial, involving educational programs and support services in rural and impoverished areas to assist women in quitting tobacco use. Furthermore, stricter regulation of the marketing and accessibility of alternative tobacco products, such as chewable tobacco, is necessary to reduce consumption. Integrating tobacco cessation programs into routine healthcare services, especially for women, can reduce tobacco use and promote healthier behaviors. Policies should also concurrently address the compounded effects of tobacco and alcohol use of NCDs. There is a need for longitudinal research to understand evolving tobacco consumption behaviors among women, considering changing societal attitudes and marketing strategies. Qualitative research exploring the cultural and social reasons behind tobacco use among women can provide crucial insights for developing culturally sensitive interventions. Additionally, more high-quality studies with large sample size from different geographical location are required. More studies are needed to investigate the relationship between healthcare access and tobacco use, and how healthcare interventions impact tobacco use behaviors. Finally, assessing the efficacy of different public health interventions and policies aimed at reducing SLT use among women is essential, including studies on the impact of educational campaigns, healthcare integration, and regulatory changes.

Our study has some limitations. One primary limitation is the restriction to articles published only in English. We searched only four databases and did not consider grey literature and non-indexed journals in our search. The sampling methods of the included studies varied, which may affect the results. Additionally, the scarcity of research specifically focusing on this demographic limit our ability to draw broad conclusions, as the number of studies exclusively examining SLT use among women of reproductive age is quite limited. Furthermore, the presence of publication bias in our study is an inevitable factor, where studies with more significant or higher prevalence rates are more likely to be published. This bias could lead to an overestimation of the prevalence of SLT use and underscores the need for more comprehensive research. Future research should delve into cultural and social factors influencing tobacco use among women, the interaction between healthcare access and tobacco habits, and the impact of specific public health interventions. Comprehensive studies are required to provide a deeper understanding of SLT use patterns and develop culturally tailored intervention programs. Research into how access to healthcare and specific healthcare interventions affect tobacco behavior is vital. Evaluating the effectiveness of various public health strategies, including educational, healthcare, and regulatory measures, is necessary to identify the most impactful approaches to reducing SLT use among women.

The study shows a significant prevalence of SLT use in women of reproductive age, especially in low socioeconomic and developing countries like India, Pakistan, and Nepal. For women of reproductive age, the use of SLT introduces additional concerns, such as infertility, complications during pregnancy, and adverse fetal outcomes, such as low birth weight and preterm birth. The results highlight the necessity for specific public health measures and policy changes to decrease SLT consumption among reproductive-age women. Further studies are needed to investigate the reasons behind SLT usage in this group and to assess the impact of intervention strategies, with the goal of guiding more effective public health initiatives and policies.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We extend our sincere appreciation to Nested Knowledge, the platform that facilitated the conduct of our systematic review.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Ramaiah Itumalla and Mahalaqua Nazli Khatib contributed equally as first authors.

Authors and Affiliations

School of Management, The Apollo University, Chittoor, 517127, Andhra Pradesh, India

Ramaiah Itumalla

Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India

Mahalaqua Nazli Khatib

One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India

Shilpa Gaidhane

South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India

Quazi Syed Zahiruddin

Jawaharlal Nehru Medical College, and Global Health Academy, School of Epidemiology and Public Health, Datta Meghe Institute of Higher Education, Wardha, India

Abhay M Gaidhane

Afghanistan Center for Epidemiological Studies, Herat, Afghanistan

Ahmad Neyazi & Ahmad Farshid Hassam

Scientific Affairs, Herat Regional Hospital, Herat, Afghanistan

Ahmad Neyazi

Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospital, Saveetha University, Chennai, India

Prakasini Satapathy

Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, 51001, Iraq

School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India

Sarvesh Rustagi

School of Pharmacy, Graphic Era Hill University, Dehradun, India

Neelima Kukreti

Department of Community Medicine, School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

Bijaya Kumar Padhi

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Substantial contribution to the conception or design of the work: R.I, B.K.P, M.N.K, S.G, AN, AFH. Acquisition of data: B.K.P, P.S, M.N.K, S.G, AN, AFH. Analysis and interpretation of data for the work: R.I, Q.S.Z, P.S, M.N.K, S.G, AN, AFH, SAR, NK.. Drafting the work: R.I., B.K.P, M.N.K, P.S. Revising it critically for important intellectual content: R.I, B.K.P, P.S, M.N.K, AMG, SAR, NK. Resources: R.I, Q.S.Z, P.S, M.N.K, B.K.P, AMG. Final approval of the version to be published: All authors (R.I., B.K.P, M.N.K, S.G, Q.S.Z, P.S, AN, AFH, SAR, NK). Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: All authors.

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Itumalla, R., Khatib, M.N., Gaidhane, S. et al. Smokeless tobacco consumption among women of reproductive age: a systematic review and meta-analysis. BMC Public Health 24 , 1361 (2024). https://doi.org/10.1186/s12889-024-18840-z

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Systematically Reviewing the Literature: Building the Evidence for Health Care Quality

There are important research and non-research reasons to systematically review the literature. This article describes a step-by-step process to systematically review the literature along with links to key resources. An example of a graduate program using systematic literature reviews to link research and quality improvement practices is also provided.

Introduction

Systematic reviews that summarize the available information on a topic are an important part of evidence-based health care. There are both research and non-research reasons for undertaking a literature review. It is important to systematically review the literature when one would like to justify the need for a study, to update personal knowledge and practice, to evaluate current practices, to develop and update guidelines for practice, and to develop work related policies. 1 A systematic review draws upon the best health services research principles and methods to address: What is the state of the evidence on the selected topic? The systematic process enables others to reproduce the methods and to make a rational determination of whether to accept the results of the review. An abundance of articles on systematic reviews exist focusing on different aspects of systematic reviews. 2 – 9 The purpose of this article is to describe a step by step process of systematically reviewing the health care literature and provide links to key resources.

Systematic Review Process: Six Key Steps

Six key steps to systematically review the literature are outlined in Table 1 and discussed here.

Systematic Review Steps

1. Formulate the Question and Refine the Topic

When preparing a topic to conduct a systematic review, it is important to ask at the outset, “What exactly am I looking for?” Hopefully it seems like an obvious step, but explicitly writing a one or two sentence statement of the topic before you begin to search is often overlooked. It is important for several reasons; in particular because, although we usually think we know what we are searching for, in truth our mental image of a topic is often quite fuzzy. The act of writing something concise and intelligible to a reader, even if you are the only one who will read it, clarifies your thoughts and can inspire you to ask key questions. In addition, in subsequent steps of the review process, when you begin to develop a strategy for searching the literature, your topic statement is the ready raw material from which you can extract the key concepts and terminology for your strategies. The medical and related health literature is massive, so the more precise and specific your understanding of your information need, the better your results will be when you search.

2. Search, Retrieve, and Select Relevant Articles

The retrieval tools chosen to search the literature should be determined by the purpose of the search. Questions to ask include: For what and by whom will the information be used? A topical expert or a novice? Am I looking for a simple fact? A comprehensive overview on the topic? Exploration of a new topic? A systematic review? For the purpose of a systematic review of journal research in the area of health care, PubMed or Medline is the most appropriate retrieval tool to start with, however other databases may be useful ( Table 2 ). In particular, Google Scholar allows one to search the same set of articles as PubMed/MEDLINE, in addition to some from other disciplines, but it lacks a number of key advanced search features that a skilled searcher can exploit in PubMed/MEDLINE.

Examples of Electronic Bibliographic Databases Specific to Health Care

Note: These databases may be available through university or hospital library systems.

An effective way to search the literature is to break the topic into different “building blocks.” The building blocks approach is the most systematic and works the best in periodical databases such as PubMed/MEDLINE. The “blocks” in a “building blocks” strategy consist of the key concepts in the search topic. For example, let’s say we are interested in researching about mobile phone-based interventions for monitoring of patient status or disease management. We could break the topic into the following concepts or blocks: 1. Mobile phones, 2. patient monitoring, and 3. Disease management. Gather synonyms and related terms to represent each concept and match to available subject headings in databases that offer them. Organize the resulting concepts into individual queries. Run the queries and examine your results to find relevant items and suggest query modifications to improve your results. Revise and re-run your strategy based on your observations. Repeat this process until you are satisfied or further modifications produce no improvements. For example in Medline, these terms would be used in this search and combined as follows: cellular phone AND (ambulatory monitoring OR disease management), where each of the key word phrases is an official subject heading in the MEDLINE vocabulary. Keep detailed notes on the literature search, as it will need to be reported in the methods section of the systematic review paper. Careful noting of search strategies also allows you to revisit a topic in the future and confidently replicate the same results, with the addition of those subsequently published on your topic.

3. Assess Quality

There is no consensus on the best way to assess study quality. Many quality assessment tools include issues such as: appropriateness of study design to the research objective, risk of bias, generalizability, statistical issues, quality of the intervention, and quality of reporting. Reporting guidelines for most literature types are available at the EQUATOR Network website ( http://www.equator-network.org/ ). These guidelines are a useful starting point; however they should not be used for assessing study quality.

4. Extract Data and Information

Extract information from each eligible article into a standardized format to permit the findings to be summarized. This will involve building one or more tables. When making tables each row should represent an article and each column a variable. Not all of the information that is extracted into the tables will end up in the paper. All of the information that is extracted from the eligible articles will help you obtain an overview of the topic, however you will want to reserve the use of tables in the literature review paper for the more complex information. All tables should be introduced and discussed in the narrative of the literature review. An example of an evidence summary table is presented in Table 3 .

Example of an evidence summary table

Notes: BP = blood pressure, HbA1c = Hemoglobin A1c, Hypo = hypoglycemic, I = Internet, NS = not significant, PDA = personal digital assistant, QOL = quality of life, SMBG = self-monitored blood glucose, SMS = short message service, V = voice

5. Analyze and Synthesize Data and information

The findings from individual studies are analyzed and synthesized so that the overall effectiveness of the intervention can be determined. It should also be observed at this time if the effect of an intervention is comparable in different studies, participants, and settings.

6. Write the Systematic Review

The PRISMA 12 and ENTREQ 13 checklists can be useful resources when writing a systematic review. These uniform reporting tools focus on how to write coherent and comprehensive reviews that facilitate readers and reviewers in evaluating the relative strengths and weaknesses. A systematic literature review has the same structure as an original research article:

TITLE : The systematic review title should indicate the content. The title should reflect the research question, however it should be a statement and not a question. The research question and the title should have similar key words.

STRUCTURED ABSTRACT: The structured abstract recaps the background, methods, results and conclusion in usually 250 words or less.

INTRODUCTION: The introduction summarizes the topic or problem and specifies the practical significance for the systematic review. The first paragraph or two of the paper should capture the attention of the reader. It might be dramatic, statistical, or descriptive, but above all, it should be interesting and very relevant to the research question. The topic or problem is linked with earlier research through previous attempts to solve the problem. Gaps in the literature regarding research and practice should also be noted. The final sentence of the introduction should clearly state the purpose of the systematic review.

METHODS: The methods provide a specification of the study protocol with enough information so that others can reproduce the results. It is important to include information on the:

• Eligibility criteria for studies: Who are the patients or subjects? What are the study characteristics, interventions, and outcomes? Were there language restrictions?
• Literature search: What databases were searched? Which key search terms were used? Which years were searched?
• Study selection: What was the study selection method? Was the title screened first, followed by the abstract, and finally the full text of the article?
• Data extraction: What data and information will be extracted from the articles?
• Data analysis: What are the statistical methods for handling any quantitative data?

RESULTS: The results should also be well-organized. One way to approach the results is to include information on the:

• Search results: What are the numbers of articles identified, excluded, and ultimately eligible?
• Study characteristics: What are the type and number of subjects? What are the methodological features of the studies?
• Study quality score: What is the overall quality of included studies? Does the quality of the included studies affect the outcome of the results?
• Results of the study: What are the overall results and outcomes? Could the literature be divided into themes or categories?

DISCUSSION: The discussion begins with a nonnumeric summary of the results. Next, gaps in the literature as well as limitations of the included articles are discussed with respect to the impact that they have on the reliability of the results. The final paragraph provides conclusions as well as implications for future research and current practice. For example, questions for future research on this topic are revealed, as well as whether or not practice should change as a result of the review.

REFERENCES: A complete bibliographical list of all journal articles, reports, books, and other media referred to in the systematic review should be included at the end of the paper. Referencing software can facilitate the compilation of citations and is useful in terms of ensuring the reference list is accurate and complete.

The following resources may be helpful when writing a systematic review:

CEBM: Centre for Evidence-based Medicine. Dedicated to the practice, teaching and dissemination of high quality evidence based medicine to improve health care Available at: http://www.cebm.net/ .

CITING MEDICINE: The National Library of Medicine Style Guide for Authors, Editors, and Publishers. This resource provides guidance in compiling, revising, formatting, and setting reference standards. Available at http://www.ncbi.nlm.nih.gov/books/NBK7265/ .

EQUATOR NETWORK: Enhancing the QUAlity and Transparency Of health Research. The EQUATOR Network promotes the transparent and accurate reporting of research studies. Available at: http://www.equator-network.org/ .

ICMJE RECOMMENDATIONS: International Committee of Medical Journal Editors Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals. The ICJME recommendations are followed by a large number of journals. Available at: http://www.icmje.org/about-icmje/faqs/icmje-recommendations/ .

PRISMA STATEMENT: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Authors can utilize the PRISMA Statement checklist to improve the reporting of systematic reviews and meta-analyses. Available at: http://prisma-statement.org .

THE COCHRANE COLLABORATION: A reliable source for making evidence generated through research useful for informing decisions about health. Available at: http://www.cochrane.org/ .

Examples of Systematic Reviews To Link Research and Quality Improvement

Over the past 17 years more than 300 learners, including physicians, nurses, and health administrators have completed a course as part of a Master of Health Administration or a Master of Science in Health Informatics degree at the University of Missouri. An objective of the course is to educate health informatics and health administration professionals about how to utilize a systematic, scientific, and evidence-based approach to literature searching, appraisal, and synthesis. Learners in the course conduct a systematic review of the literature on a health care topic of their choosing that could suggest quality improvement in their organization. Students select topics that make sense in terms of their core educational competencies and are related to their work. The categories of topics include public health, leadership, information management, health information technology, electronic medical records, telehealth, patient/clinician safety, treatment/screening evaluation cost/finance, human resources, planning and marketing, supply chain, education/training, policies and regulations, access, and satisfaction. Some learners have published their systematic literature reviews 14 – 15 . Qualitative comments from the students indicate that the course is well received and the skills learned in the course are applicable to a variety of health care settings.

Undertaking a literature review includes identification of a topic of interest, searching and retrieving the appropriate literature, assessing quality, extracting data and information, analyzing and synthesizing the findings, and writing a report. A structured step-by-step approach facilitates the development of a complete and informed literature review.

Suzanne Austin Boren, PhD, MHA, (above) is Associate Professor and Director of Academic Programs, and David Moxley, MLIS, is Clinical Instructor and Associate Director of Executive Programs. Both are in the Department of Health Management and Informatics at the University of Missouri School of Medicine.

Contact: ude.iruossim.htlaeh@snerob

None reported.

A systematic literature review of the epidemiology and burden of herpes zoster in selected locales in Asia Pacific

Affiliations.

• 1 Epidemiology and Health Outcomes, GSK, Singapore.
• 2 Salmon Bay Epidemiology Consulting LLC, Seattle, WA, USA.
• 3 Medical Affairs, GSK, Wavre, Belgium.
• PMID: 38767209
• DOI: 10.1080/21645515.2024.2344983

Herpes zoster (HZ) is a painful rash which typically affects older adults. This is of concern in Asia-Pacific given its aging population. As HZ epidemiology and burden are evolving, this systematic literature review aimed to update the current understanding of HZ burden and associated costs for selected Asia-Pacific locales. MEDLINE and Embase were searched for English articles of HZ studies conducted in Australia, China, Hong Kong, Japan, Korea, New Zealand, Singapore, and Taiwan. Eligible outcomes included HZ incidence and prevalence, occurrence of HZ-related complications, healthcare resource utilization, costs, and HZ-associated quality of life outcomes. This paper focused on HZ data in the general adult population ( N = 90 articles). Substantial HZ-related disease and economic burden were observed in these locales, consistent with global trends. These findings reinforce the increasing burden of HZ and need for preventive strategies, which may include raising awareness and encouraging timely vaccination.

Keywords: Asia-Pacific; Herpes zoster; complications; epidemiology; healthcare burden; shingles; systematic literature review.

Plain language summary

Herpes zoster, also known as shingles, is a painful rash that usually resolves after a few weeks, although some people experience serious or long-lasting complications. Shingles is common, affecting around one in every three individuals in their lifetime, and older persons are more likely to have shingles. Given the aging population in the Asia-Pacific region, shingles represents an increasingly important health issue as the proportion of older people increases. Vaccination can help prevent shingles and avoid its complications. New data on the trends and burden of shingles in this region are regularly generated. Therefore, in this study, we looked at studies from selected countries published over the past twenty years to summarize the latest available information on: how many people experience shingles in selected Asia-Pacific areas, how these individuals and societies are affected, and the related costs. Consistent with previous research, this study observed an increasing trend in the number of persons with shingles and costs of managing it, especially in older adults. In populations that are aging, there is a need for ways to reduce the risk of shingles and to lessen its burden on the healthcare system and society. Our findings can help to inform current development of strategies to reduce the risk of shingles, including education (on the burden and risk of shingles) and encouraging uptake of preventive measures.

Publication types

• Systematic Review
• Asia / epidemiology
• Australia / epidemiology
• Cost of Illness*
• Herpes Zoster* / economics
• Herpes Zoster* / epidemiology
• Middle Aged
• New Zealand / epidemiology
• Quality of Life

• Open access
• Published: 17 May 2024

The impact of armed conflicts on HIV treatment outcomes in Sub-Saharan Africa: a systematic review and meta-analysis

• Hafte Kahsay Kebede 1 , 2 , 3 ,
• Hailay Abrha Gesesew 2 , 3 ,
• Amanuel Tesfay Gebremedhin 4 , 5 &
• Paul Ward 3  

Conflict and Health volume  18 , Article number:  40 ( 2024 ) Cite this article

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Despite the fact that Sub-Saharan Africa bears a disproportionate burden of armed conflicts and HIV infection, there has been inadequate synthesis of the impact of armed conflict on HIV treatment outcomes. We summarized the available evidence on the impact of armed conflicts on HIV treatment outcomes in Sub-Saharan Africa from 2002 to 2022.

We searched four databases; MEDLINE, PubMed, CINHAL, and Scopus. We also explored grey literature sources and reviewed the bibliographies of all articles to identify any additional relevant studies. We included quantitative studies published in English from January 1, 2002 to December 30, 2022 that reported on HIV treatment outcomes for patients receiving antiretroviral therapy (ART) in conflict and post-conflict areas, IDP centers, or refugee camps, and reported on their treatment outcomes from sub-Saharan Africa. Studies published in languages other than English, reporting on non-ART patients and reporting on current or former military populations were excluded. We used EndNote X9 and Covidence to remove duplicates, extracted data using JBI-MAStARI, assessed risk of bias using AHRQ criteria, reported results using PRISMA checklist, and determined Statistical heterogeneity using Cochran Q test and Higgins I 2 , R- and RevMan-5 software were used for meta-analysis.

The review included 16 studies with participant numbers ranging from 102 to 2572. Lost To Follow-Up (LTFU) percentages varied between 5.4% and 43.5%, virologic non-suppression rates ranged from 25 to 33%, adherence rates were over 88%, and mortality rates were between 4.2% and 13%. A pooled meta-analysis of virologic non-suppression rates from active conflict settings revealed a non-suppression rate of 30% (0.30 (0.26–0.33), I2 = 0.00%, p  = 0.000). In contrast, a pooled meta-analysis of predictors of loss to follow-up (LTFU) from post-conflict settings identified a higher odds ratio for females compared to males (1.51 (1.05, 2.17), I2 = 0%, p  = 0.03).

The review highlights a lack of research on the relationship between armed conflicts and HIV care outcomes in SSA. The available documents lack quality of designs and data sources, and the depth and diversity of subjects covered.

Introduction

Armed conflicts have a negative impact on the health of populations, particularly on HIV patients who require strict adherence to treatment [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Providing regular HIV care and ensuring a continuous supply of drugs in conflict zones is difficult [ 2 ], leading to increased HIV incidence, prevalence, and related morbidity and mortality[ 8 9 ]. Less than 20% of people in conflict situations receive ART [ 10 ], and HIV services are scarce or nonexistent in conflict-affected countries; such as the Central African Republic (CAR), South Sudan, and parts of Yemen [ 10 ]. With 1.8 billion people living in conflict-affected areas [ 11 ], and 89.3 million people displaced from their homes by the end of 2021[ 12 ], researchers need to investigate how war affects HIV treatment.

However, there is a lack of systematic reviews investigating the connection between HIV and conflict, including the impact of armed conflict on HIV treatment outcomes. There were few systematic reviews[ 9 13 , 14 , 15 , 16 , 17 ] that have paid close attention to HIV prevalence and incidence as a result of armed conflict. None of the systematic reviews assessed the impact of armed conflict on HIV treatment outcomes. Given the importance of HIV treatment in reducing HIV incidence and prevalence, the double burden of HIV and conflict in Sub-Saharan Africa, and the already fragile healthcare system in the region, there is a need for systematic synthesis and exploration of this area of research. This review aims to synthesize the impact of armed conflict on HIV treatment outcomes among HIV patients affected by armed conflicts in SSA, including retention, attrition, LTFU, clinical failure, immunological failure, treatment failure, virological failure, and mortality.

Study registration

The review was registered in the International Prospective Register for Systematic Reviews (PROSPERO), with the registration number CRD42022361924 and the protocol is published online in BMJ Open [ 18 ].

Population and context

The review included individuals in sub-Saharan Africa who received antiretroviral therapy between 2002 and 2022 and were living in conflict-affected, post-conflict, or displacement areas. We selected 2002, as many sub-Saharan African countries introduced HIV care and treatment programs in 2002[ 19 ]. The review was limited to sub-Saharan Africa due to the region’s disproportionately high affected by both HIV infection [ 20 ] and armed conflicts[ 16 21 , 22 , 23 , 24 ] (Fig.  1 ), weak healthcare systems, and lack of clear directives and funding for addressing HIV care in conflict-affected settings.

(Source: UCDP Version 2021)

Number of conflict-affected and conflict incidents in sub-Saharan Africa between 2002 and 2021.

Search strategy and data sources

The search was conducted using three themes: conflict, HIV care, and SSA, and was conducted in four databases. Although the initial plan was to search five databases, access to Web of Sciences was not possible. After seeking advice from our librarian, we chose to exclude Web of Sciences from our search since it had comparable literature content to SCOPUS. Consequently, we searched the remaining four databases, which included MEDLINE, PubMed, CINHAL, and SCOPUS. We also explored grey literature sources and reviewed the bibliographies of all articles to identify any additional relevant studies.

Study selection and eligibility criteria

The study only included quantitative studies conducted in English from January 1, 2002 and December 31, 2022 that focused on HIV patients receiving ART from conflict areas, IDP centers, or refugee camps, and reported on their treatment outcomes. Studies that included both conflict-affected and non-conflict-affected populations were only included if they provided data specifically for the conflict-affected group. Studies published in languages other than English, those that did not mention conflict or provide disaggregated data for conflict-affected populations, studies that involved current or former military populations, studies from countries outside of SSA, studies reporting on African refugees settled outside of SSA, studies published before 2002, and studies reporting on HIV patients not receiving ART were excluded.

Quality assessment

The search results were filtered through a multi-step process that included independent review by two reviewers, evaluation of methodological validity using standardized JBI appraisal instruments [ 25 ], and assessment of risk of bias using AHRQ criteria [ 26 ]. Disagreements among reviewers were resolved through discussion and consensus but included and extracted data from all relevant documents irrespective of their quality score.

Data extraction

We used EndNote X9 and Covidence to remove duplicates. Data were extracted using the standardized data extraction tool from JBI-MAStARI [ 27 ]. The data extracted included specific details about the authors, publication year, country of study, populations, sample size, summary of HIV treatment outcome.

Types of interventions and comparators

The review considered impact of armed conflict on HIV treatment outcomes.

Types of outcome measures

The study focused on HIV care treatment outcomes, including adherence, LTFU, clinical failure, immunological failure, virological failure, and mortality.

Operational definitions

There is no universally accepted definition of armed conflict, as it is an umbrella word for a wide range of ideas and activities, such as conflict, war, violence, terrorism, or catastrophic loss of civilian life, a civil unrest, massive displacement, and violations of human rights and international humanitarian law. While we put the definition of conflict as follows, we would like to remain open to additional definitions by authors.

• Armed conflict

Is a situation in which states or other organized parties fight against each other by way of military force. Armed conflicts shall be of international and non-international armed conflicts [ 28 ].

Conflict affected areas

Are areas experiencing an armed conflict, and post-conflict regions. The area may be a region, a country, an area within a country, or an area that crosses one or more country boundaries. The impact of conflict may extend beyond the region of conflict to include surrounding areas and those hosting displaced persons. As a result, our definition remains open to the definition of authors.

Conflict -affected populations

Individuals, groups, and communities affected by and remaining in conflict-affected areas, as well as those forcibly displaced from them as refugees and IDPs. Conflict may have an impact on those who host IDPs and refugees. As a result, our definition remains open to author definition.

Internally displaced persons (IDPs)

Those who have been forced or compelled to leave their homes, often due to armed conflict, and who stay within their country’s borders.

Post-conflict

Refers to the period immediately following a conflict, when open combat is over. Nevertheless, despite its linguistic simplicity, the phrase is more challenging to define practically in terms of time, response, transformation, and sustainability. Therefore, our definition remains open to author definition.

People who are outside their country of birth due to conflict, war, widespread violence, or feared persecution and who as a result need international protection within the African continent [ 29 ].

Data management, analysis and synthesis

The results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [ 30 ] and meta regression was done to assess the relationship between armed conflict and HIV treatment outcomes. The Cochran Q test and Higgins I 2 [ 31 ] were used to determine statistical heterogeneity, and the random effect model was used when moderate statistical heterogeneity was detected. A meta-analysis to assess the predictors of LTFU was also conducted. The study used various statistical tools and software for analysis; R- software, STATA, and RevMan-5.

Outcome of the search

The comprehensive search identified 2487 records; 2332 identified through database searches, and 155 through manual searching of references and websites identified. All the identified 2487 references were exported into EndNote X9, and then into Covidence; 171 in the endnote, and 181 articles in the Covidence duplications were removed. After eliminating duplicates and conducting a comprehensive screening using Covidence was done, and 16 studies were considered eligible for data extraction, with 10 of them providing data for meta-analysis (Fig.  2 ).

PRISMA flowchart diagram of study selection impact of armed conflict on HIV care outcomes in SSA, 2002–2022

Description of included studies

The research covered in the review spanned from 2007[ 32 ] to 2022[ 33 ] and had varying follow-up periods, ranging from 4 days [ 34 ] to 60 months [ 35 ]. The majority of the studies were conducted in Western and Eastern Africa, with a significant number of studies coming from the Democratic Republic of the Congo[ 32 33 35 , 36 , 37 ], Kenya [ 38 , 39 , 40 ], and Uganda[ 34 41 42 ]. Most of the studies were designed as cohort studies, either retrospective[ 32 35 38 , 39 , 40 , 41 43 , 44 , 45 ] or prospective[ 33 36 37 42 46 ]. The majority of the studies focused on adult populations[ 33 , 34 , 35 , 36 , 37 39 40 42 , 43 , 44 ], with one study [ 38 ] specifically examining children. The studies included patients who were non-IDPs[ 32 33 35 , 36 , 37 , 38 40 41 ], non-IDPs & IDPs[ 34 39 42 44 45 ], refugees[ 44 47 ], or a mix of these groups [ 43 ]. Ten studies were carried out in conflict settings[ 32 , 33 , 34 36 37 42 44 , 45 , 46 , 47 ], while five took place in post-conflict zones[ 35 38 , 39 , 40 , 41 ], and one in both [ 43 ] (Table  1 and Supplementary Table 1 ).

Quality assessment—Data aource/Validity/Reliability

Methodological validity of the included studies was evaluated using JBI appraisal instruments. The quality of evidence was rated as high quality ( n  = 7, 90.91%, n  = 5, 81.82%, n  = 1, 100%, n  = 1, 90%, n  = 1, 75%, n  = 1, 72.73%) and presented moderate quality. The outcomes of the BJI assessment are shown in supplementary (supplementary Table 2 ).

Conflict and HIV treatment outcomes

The studies reported various outcomes, with four[ 33 36 37 46 ] focusing on the relationship between conflict and HIV treatment outcome as the primary outcome, five reporting adherence rates[ 32 34 38 42 44 ], two reporting treatment interruption[ 39 40 ], nine reporting LTFU[ 32 35 36 38 41 43 45 , 46 , 47 ], four reporting immunologic gain[ 32 40 42 43 ], four looking at the rate of viral non-suppression[ 37 40 45 47 ], and seven reporting mortality[ 32 33 35 42 43 46 47 ] (Supplementary Table 3 ).

The review found that adherence rates among HIV patients in Sub-Saharan Africa ranged from 88.2%[ 44 ] to 99.6%[ 34 ]. The studies reported predictors of non-adherence, and non-adherence was associated with being on first-line therapy(OR = 22.22, 95% CI 1.53, 333.33; p  = 0.02)[ 34 ], and feeling condemned by clinic workers (OR = 22.22, 95%CI 1.53, 333.33; p  = 0.02)[ 34 ].

Pooled meta-analysis

The pooled adherence rate among HIV patients in conflict-affected SSA regions was 0.06 (0.02–0.12), I2 = 87.12%, p  = 0.00, with a significant clinical heterogeneity (Fig.  3 ).

Pooled meta-analysis of non-adherence rate from active conflict settings among HIV patients who were on ART in SSA from 2002 to 2022

Treatment interruption (TI)

Two studies[ 39 40 ] conducted in Kenya reported instances of treatment interruption, with the risk of interruption increasing by 71% during post-election violence (95%CI 34, 118, p  = 0.001). Male patients (OR = 1.37, 95%CI 1.07, 1.76; p  = 0.01), and who traveled more than three hours to the clinic (OR = 1.86, 95%CI 1.28, 2.71; p  = 0.001) were found to be at a higher risk of treatment interruption [ 39 ]. Treatment interruptions were associated with detectable viral load, with viral loads exceeding 5,000 copies/mL and 10,00060 copies/mL[ 40 ].

Lost to follow-up

In active conflict settings, the rate of loss to follow-up (LTFU) ranged from 5.4% (95% CI = 3.2–7.5)[ 32 ] to 28.8% (95% CI: 24.9–33.1) [ 36 ], while post-conflict areas had a paradoxical level of LTFU ranging from 2.6%[ 38 ] to 43.5%[ 41 ]. The included studies indicated that factors like educational level [ 36 ], place of residence [ 36 ], prior experience with antiretroviral therapy (ART) upon enrollment [ 36 ], and the World Health Organization (WHO) clinical stage of disease [ 41 ] were linked to loss to follow-up (LTFU) among adult patients. Additionally, the study showed that receiving ART reduced the likelihood of complete loss to follow-up among children with HIV in post-crisis Kenya [ 38 ].

Pooled LTFU rates of 0.16 (0.08–0.28), I2 = 98.55%, p  = 0.00 were found in studies from active conflict settings[ 32 36 46 47 ], (Fig.  4 ), and 0.16(0.01–0.42), I2 = 99.52%, p  = 0.00 post-conflict settings[ 35 38 41 ] (Fig.  5 ).

Pooled meta-analysis of LTFU rate from active conflict settings among HIV patients who were on ART in SSA from 2002 to 2022

Pooled meta-analysis of LTFU rate from post conflict settings among HIV patients who were on ART in SSA from 2002 to 2022

Similarly, a review of studies conducted in post-conflict settings analyzed factors that may predict loss to follow-up (LTFU) in HIV care. The study found that only gender was statistically significant, with a 1.51 (1.05, 2.17), I 2  = 0%, P  = 0.03 odds ratio for LTFU in females compared to males (Fig.  6 ).

Meta-analysis of predictors of LTFU in post conflict-settings among HIV patients who were on ART in SSA from 2002 to 2022

Immunologic gain

CD4 gain was reported by four studies[ 32 40 42 43 ], as a secondary outcome, with changes ranging from 129 mm3[ 43 ] to a median of 163 cells/mm 3 [ 32 ] in six months.

Viral non-suppressions

Four studies examined the prevalence of viral non-suppression[ 37 40 45 47 ], with different thresholds ranging from > 50[ 45 47 ] to > 1000 copies/mL[ 45 47 ]. Three studies[ 37 45 47 ] investigated predictors of viral non-suppression, with two finding no significant variables and one [ 37 ] reporting that being in stage III or IV of the disease (AOR = 1.86, 95% CI 1.01–3.43), and having a high baseline HIV viremia of over 1000 copies/mL(AOR = 3.41, 95% CI 1.64–7.08) were associated with increased risk [ 37 ].

A pooled-analysis of two studies[ 45 47 ] from active conflict settings found a pooled non-suppression rate of 30% (0.30(0.26–0.33), I2 = 0.00%, p  = 0.000) using a cut-off point of > 1000 copies/mL and a follow-up period of 6–12 months (Fig.  7 ).

Pooled meta-analysis of virologic non-suppression rate from active conflict settings among HIV patients who were on ART in SSA from 2002 to 2022

Seven studies provided information on mortality rates, with five conducted in active conflict settings[ 32 33 42 46 47 ], and one each in post-conflict [ 35 ] and both conflict and post-conflict [ 43 ] settings. Mortality rates ranged from 3.6% (17/468)[ 33 ] to 13.0% (182/1400)[ 47 ]. Three studies[ 33 46 42 ] examined predictors of mortality namely, socio-demographic variables such as age and sex, as well as clinical variables such as baseline ART status, viral load, CD4 count, WHO clinical stage, and adherence level were reported having associated with lower risk of mortality.

A pooled-analysis of five studies from active conflict settings showed a pooled mortality rate of 0.07 (0.04–0.11), I2 = 95.84%, p  = 0.00), indicating high clinical heterogeneity (Fig.  8 ).

Pooled meta-analysis of mortality rate from active conflict settings among HIV patients who were on ART in SSA from 2002 to 2022

This systematic review included 16 articles published from 2002 to 2022. To the best of our knowledge, this systematic review is one of the first comprehensive reviews to assess quantitative studies in seeking to address the substantial gaps in current knowledge regarding the impact of armed conflict on HIV care outcomes in SSA.

Despite the anticipated challenges in accessing ART medication and care schedules in conflict settings[ 16 32 48 ], such as ARV medications running out, lack of or poor access to health services, a shortage of medical professionals, and an increased burden of other medical priorities, along with the expected negative impact on HIV care outcomes[ 16 32 49 ]; the systematic review found lower rates of non-adherence, loss to follow-up, virologic non-suppression, and mortality compared to those reported from politically stable and well-resourced regions in Sub-Saharan Africa[ 43 50 , 51 , 52 , 53 , 54 ].

Furthermore, the pattern of unfavourable clinical outcomes among those HIV patients in ART reported in the included studies is driven more strongly by patient level covariates than by the evolution of the surrounding long-term conflict, socioeconomic factors[ 35 39 ], socioeconomic and clinical factors[ 33 37 42 46 ], and clinical variables[ 34 36 40 ], and these findings correspond to those of previous research in low-income countries, which also found that unfavourable clinical outcomes were associated with patient age, baseline VL, and the status of treatment before enrollment [ 53 ]. This suggests that the cause of poor clinical outcomes was likely not to have been related to armed conflict and associated factors.

The inconsistency of the studies with the perceived outcomes reflects the complex interrelationship between conflict and HIV care. Many factors could have contributed to the disparity in perceived HIV care outcomes and conflict. These include, patient commitment and creativity in obtaining treatment[ 32 34 38 39 42 ], as well as education about the benefits of treatment, contribute to positive clinical outcomes. Furthermore, the results of the included studies might have been influenced by information bias, as the impact of conflict-related factors on HIV care was not taken into account. conflict could lead to a range of indirect factors that negatively affect the HIV care outcomes; such as, lack of access to safe drinking water, food insecurity, social unrest, displacement, insecurity, and destruction of livelihoods, psychosocial trauma, and the inability of health systems and other social services[ 16 39 48 55 ].

Additionally, the studies themselves had limitations, including retrospective design which rely heavily on patient charts which may have missing data and possible information bias, simplistic study (cause and effect) approach, bias in representativeness as majority of the studies were reported from NGOs funded and managed IDP sites, and a focus on adult populations rather than vulnerable groups like children. These non-governmental organizations (NGOs) are concentrated in small, stable areas. They had a small number of patients in them. The studies were also limited by their small geographic scope. The majority of HIV-infected people, however, live in remote villages.

Therefore, the systematic review highlights the limited research on the relationship between armed conflict and HIV care outcomes in Sub-Saharan Africa. Despite high double burden of armed conflicts and HIV infection in Sub-Saharan Africa, the extensive systematic search revealed that there is limited research on the relationship between armed conflict and HIV care outcomes in Sub-Saharan Africa, with only 16 eligible studies found (Fig.  9 ). This could be due to the belief that providing ART and conducting research during conflict is too difficult [ 48 ]. Furthermore, the existing studies focus on a limited geographic scope and adopt a simplistic cause-and-effect approach, failing to capture the complex and contentious relationship between conflict and HIV care outcomes in SSA. Additionally, the available studies failed to consider the conflict related factors, and indirect factors, post conflict settings. Additionally, pediatrics and mothers were also neglected in the available studies. The available studies fall short of addressing the realities of HIV care in conflict settings, and more research is needed to understand the impacts of armed conflicts on HIV care outcomes, especially in sub-Saharan Africa. Therefore, more research is needed to understand the reciprocal relationship between conflict and HIV care outcomes in Sub-Saharan Africa. Details of the recommended research areas are tabled in Table  2 .

Mapping conflict events, and locations where studies on the impact of armed conflicts on HIV care outcomes were published, SSA between 2002 and 2021. (source: UCDP Version 21)

This systematic review filled a gap in study on HIV treatment outcomes in conflict zones in Sub-Saharan Africa. However, the review highlights a lack of research on the relationship between armed conflicts and HIV care outcomes in Sub-Saharan Africa. The available documents lack quality of designs and data sources, and depth and diversity of subjects covered; calling further primary studies on a prioritized future research agenda. Furthermore, there were possible limitations to the review, including there might be exclusion of studies not labeled as conflict-related, selection bias due to language limitations (the database search was limited to English), and potential confounding variables of which we are unaware might be present.

Data availability

All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.

Abbreviations

Anti-Retroviral Therapy

Human Immuno-Deficiency Virus

Internally Displaced People

Lost To Follow-Up

Ministry of Health

Non-Governmental Organizations

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Hafte Kahsay Kebede

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H.K.K performed the search, and employed screening and data extraction with H.A.G independently. All authors have full access to all the data in the study and have final responsibility for the decision to submit for publication. Study concept and design: P.R.W, H.A.G, H.K.K. Acquisition, analysis, or interpretation of data: P.R.W, H.A.G, H.K.K. Drafting of the manuscript: H.K.K. Critical revision of the manuscript for important intellectual content: P.R.W, H.A.G, H.K.K Meta- analysis, and mapping: A.T.G, H.K.K.Study supervision: P.R.W, H.A.G.

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Kebede, H.K., Gesesew, H.A., Gebremedhin, A.T. et al. The impact of armed conflicts on HIV treatment outcomes in Sub-Saharan Africa: a systematic review and meta-analysis. Confl Health 18 , 40 (2024). https://doi.org/10.1186/s13031-024-00591-8

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