Pharmacogenomics of Drugs Used in ß-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications.

In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of ß-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the HBG2 XmnI polymorphism and those related to the BCL11A, MYB, KLF-1, and LYAR genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.

Implementation science research for the scale-up of evidence-based interventions for sickle cell disease in africa: a commentary.

BACKGROUND: The burden of sickle cell disease (SCD) is greatest among African nations. Effective scalability of evidence-based interventions (e.g., newborn screening, health education, prophylaxis for infection, optimal nutrition and hydration, hydroxyurea therapy, blood transfusions, and transcranial Doppler (TCD) screening) is urgently needed particularly in these settings for disease management. However, Africa is constrained by limited resources and the lack of capacity to conduct implementation science research for proper understanding of context, and assessment of barriers and facilitators to the uptake and scalability of evidence-based interventions (EBI) for SCD management. MAIN BODY: We outline implementation science approaches to embed EBI for SCD within the African context and highlight key implementation research programs for SCD management. Building implementation research capacity will meet the major need of developing effective life-long and accessible locally-tailored interventions for patients with SCD in Africa. CONCLUSION: This commentary communicates the importance of the application of implementation science methodology to scale-up evidence-based interventions for the management of SCD in order to reduce pain, prevent other morbidities and premature death experienced by people with SCD in Africa, and improve their overall quality of life.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Application of the Consolidated Framework for Implementation Research to examine nurses' perception of the task shifting strategy for hypertension control trial in Ghana.

BACKGROUND: The burden of hypertension in many low-and middle-income countries is alarming and requires effective evidence-based preventative strategies that is carefully appraised and accepted by key stakeholders to ensure successful implementation and sustainability. We assessed nurses' perceptions of a recently completed Task Shifting Strategy for Hypertension control (TASSH) trial in Ghana, and facilitators and challenges to TASSH implementation. METHODS: Focus group sessions and in-depth interviews were conducted with 27 community health nurses from participating health centers and district hospitals involved in the TASSH trial implemented in the Ashanti Region, Ghana, West Africa from 2012 to 2017. TASSH evaluated the comparative effectiveness of the WHO-PEN program versus provision of health insurance for blood pressure reduction in hypertensive adults. Qualitative data were analyzed using open and axial coding techniques with emerging themes mapped onto the Consolidated Framework for Implementation Research (CFIR). RESULTS: Three themes emerged following deductive analysis using CFIR, including: (1) Patient health goal setting- relative priority and positive feedback from nurses, which motivated patients to make healthy behavior changes as a result of their health being a priority; (2) Leadership engagement (i.e., medical directors) which influenced the extent to which nurses were able to successfully implement TASSH in their various facilities, with most directors being very supportive; and (3) Availability of resources making it possible to implement the TASSH protocol, with limited space and personnel time to carry out TASSH duties, limited blood pressure (BP) monitoring equipment, and transportation, listed as barriers to effective implementation. CONCLUSION: Assessing stakeholders' perception of the TASSH implementation process guided by CFIR is crucial as it provides a platform for the nurses to thoroughly evaluate the task shifting program, while considering the local context in which the program is implemented. The feedback from the nurses informed barriers and facilitators to implementation of TASSH within the current healthcare system, and suggested system level changes needed prior to scale-up of TASSH to other regions in Ghana with potential for long-term sustainment of the task shifting intervention. TRIAL REGISTRATION: Trial registration for parent TASSH study: NCT01802372. Registered February 27, 2013.

Addressing gaps in international blood availability and transfusion safety in low- and middle-income countries: a NHLBI workshop.

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs.

Foreword: Big Data and Its Application in Health Disparities Research.

The articles presented in this special issue advance the conversation by describing the current efforts, findings and concerns related to Big Data and health disparities. They offer important recommendations and perspectives to consider when designing systems that can usefully leverage Big Data to reduce health disparities. We hope that ongoing Big Data efforts can build on these contributions to advance the conversation, address our embedded assumptions, and identify levers for action to reduce health care disparities.

Big Data Science: Opportunities and Challenges to Address Minority Health and Health Disparities in the 21st Century.

Addressing minority health and health disparities has been a missing piece of the puzzle in Big Data science. This article focuses on three priority opportunities that Big Data science may offer to the reduction of health and health care disparities. One opportunity is to incorporate standardized information on demographic and social determinants in electronic health records in order to target ways to improve quality of care for the most disadvantaged populations over time. A second opportunity is to enhance public health surveillance by linking geographical variables and social determinants of health for geographically defined populations to clinical data and health outcomes. Third and most importantly, Big Data science may lead to a better understanding of the etiology of health disparities and understanding of minority health in order to guide intervention development. However, the promise of Big Data needs to be considered in light of significant challenges that threaten to widen health disparities. Care must be taken to incorporate diverse populations to realize the potential benefits. Specific recommendations include investing in data collection on small sample populations, building a diverse workforce pipeline for data science, actively seeking to reduce digital divides, developing novel ways to assure digital data privacy for small populations, and promoting widespread data sharing to benefit under-resourced minority-serving institutions and minority researchers. With deliberate efforts, Big Data presents a dramatic opportunity for reducing health disparities but without active engagement, it risks further widening them.

A Strategic Framework for Utilizing Late-Stage (T4) Translation Research to Address Health Inequities.

Achieving health equity requires that every person has the opportunity to attain their full health potential and no one is disadvantaged from achieving this potential because of social position or other socially determined circumstances. Inequity experienced by populations of lower socioeconomic status is reflected in differences in health status and mortality rates, as well as in the distribution of disease, disability and illness across these population groups. This article gives an overview of the health inequities literature associated with heart, lung, blood and sleep (HLBS) disorders. We present an ecological framework that provides a theoretical foundation to study late-stage T4 translation research that studies implementation strategies for proven effective interventions to address health inequities.

A Global Perspective on Using Implementation Research to Address Hypertension-Associated Target Organ Damage.

Hypertension, a major risk factor for cardiovascular disease, imposes a significant public health burden and challenge to address it worldwide. Scaling up delivery of proven, effective interventions for hypertension could significantly advance the goal of reducing the global burden. Although significant progress has been made in many countries, some lament that large-scale initiatives focused on reducing blood pressure in global populations have not effectively addressed this challenge. Late-stage implementation research plays a critical role in determining effective and sustainable scale-up of these initiatives. In this article, we briefly discuss some of the global initiatives that have been funded by the National Heart, Lung, and Blood Institute of the US National Institutes of Health. Intervention delivery strategies in low resource settings must have demonstrated effectiveness and consideration for the social, cultural and physical context (eg, access, affordability, and availability of medications) in which a program is being delivered in order to be sustainable nationally and globally. Hence, the use of implementation research is central to determining sustainable delivery of evidence-based and tailored interventions focused on hypertension control. The sustained control of hypertension in global populations holds tremendous potential for reducing morbidity, premature mortality, and the adverse economic impact of cardiovascular disease in all regions.

Understanding decreased fertility in women carriers of the FMR1 premutation: a possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency (FXPOI).

Fragile X syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine-guanine (CGG) triplet repeats, causes FXS. Individuals with 55-199 CGG repeats, classified as premutation carriers, are affected by two distinct disorders depending on their premutation status. Disorders associated with premutation carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similarities of FXTAS and FXPOI (e.g. overabundance of FMR1 transcript and intranuclear inclusions) suggest that similar molecular mechanisms underlie both FXTAS and FXPOI. The current hypothesis describes the underlying mechanism for FXTAS as an mRNA gain-of-function mutation, however the underlying mechanism for FXPOI remains unresolved. New data suggests that repeat associated non-AUG (RAN) translation could underlie FXPOI.

How College Students Used Information From Institutions of Higher Education in the United States During COVID-19: Web-Based Cross-Sectional Survey Study.

BACKGROUND: The start of the COVID-19 pandemic resulted in the implementation of nonpharmaceutical interventions by US institutions of higher education at an unprecedented level. During the backdrop of an emerging pandemic, younger adults (eg, college students) had an overall lower risk for severe outcomes for SARS-CoV-2, making this population a potential source of transmission for age groups with high susceptibility and negative health outcomes. We examine how college students' level of concern for COVID-19 was influenced by different sources of information, their living status, income level, and other demographic identifiers and its association with prevention behavior change. OBJECTIVE: We sought to examine the level of concern, defined as the extent to which the participant would take corrective action to mitigate contracting or spreading the virus (to family or friends) by using personal protective equipment such as a face mask, practicing social distancing, and following other public health recommendations, among college students during the COVID-19 pandemic. METHODS: A cross-sectional, web-based survey was conducted in 2021 among 185 college students aged 18-41 years, with most living in New York City and the United States (n=134, 72.4%). Out of 185 college students, 94 provided their zip codes, with 51 of those college students indicating they lived in New York City areas. The participants completed the survey via a QR code. Study participants who did not complete the full survey or were not college students in any US college or university were excluded. Analyses were conducted using R (version 4.2.2; R Foundation for Statistical Computing). RESULTS: Of 185 respondents participated in the study, 25 (13.5.%) used emails from their schools, 51 (27.6%) used mainstream media, and 109 (58.9%) used social media and other sources to obtain information about COVID-19. Of the 109 participants who learned about the pandemic from social media, 91 (83.5%) were concerned; however, only 63% (32/51) and 60% (15/25) of the participants who sourced information from mainstream media and their schools' email, respectively, were concerned. Further, the participants who received information from social media and other sources were about 3 times more likely to be concerned about COVID-19 than participants who received information from the university via email (P=.036; OR=3.07, 95% CI: 1.06-8.83).. CONCLUSIONS: College students who received information from social media and other sources were more likely to be concerned about COVID-19 than students who received information from their school via emails.

Biomedical research, a tool to address the health issues that affect African populations.

Traditionally, biomedical research endeavors in low to middle resources countries have focused on communicable diseases. However, data collected over the past 20 years by the World Health Organization (WHO) show a significant increase in the number of people suffering from non-communicable diseases (e.g. heart disease, diabetes, cancer and pulmonary diseases). Within the coming years, WHO predicts significant decreases in communicable diseases while non-communicable diseases are expected to double in low and middle income countries in sub-Saharan Africa. The predicted increase in the non-communicable diseases population could be economically burdensome for the basic healthcare infrastructure of countries that lack resources to address this emerging disease burden. Biomedical research could stimulate development of healthcare and biomedical infrastructure. If this development is sustainable, it provides an opportunity to alleviate the burden of both communicable and non-communicable diseases through diagnosis, prevention and treatment. In this paper, we discuss how research using biomedical technology, especially genomics, has produced data that enhances the understanding and treatment of both communicable and non-communicable diseases in sub-Saharan Africa. We further discuss how scientific development can provide opportunities to pursue research areas responsive to the African populations. We limit our discussion to biomedical research in the areas of genomics due to its substantial impact on the scientific community in recent years however, we also recognize that targeted investments in other scientific disciplines could also foster further development in African countries.

Reducing Dietary Sodium Intake among Young Adults in Ghana: A Call to Action.

The positive association between excessive dietary sodium intake, hypertension, and cardiovascular disease (CVD) has been widely investigated in observational studies and clinical trials. Reducing sodium intake is a proven strategy to prevent hypertension and the onset of CVD, a major cause of morbidity and mortality globally. Africa has the youngest population globally, which is key to the continent's sustainable development. However, in Africa, the epidemics of hypertension and CVD negatively impact life expectancy and economic growth. Ghana, like other African countries, is no exception. The factors contributing to the increasing burden of CVD and excessive sodium consumption are multi-faceted and multi-level, including individual lifestyle, neighborhood and built environments, and socio-economic and health policies. Thus, the implementation of evidence-based interventions such as the World Health Organization Best Buys that target the multi-level determinants of sodium consumption is urgently needed in Ghana and other African countries. The aim of this commentary is to highlight factors that contribute to excessive sodium consumption. Second, the commentary will showcase lessons of successful implementation of sodium reduction interventions in other countries. Such lessons may help avert CVD in young adults in Ghana and Africa.

Implementation of non-insulin-dependent diabetes self-management education (DSME) in LMICs: a systematic review of cost, adoption, acceptability, and fidelity in resource-constrained settings.

Background: Type II diabetes (T2D), is a serious health issue accounting for 10.7% of mortality globally. 80% of cases worldwide are found in low- and middle-income countries (LMIC), with rapidly increasing prevalence. Diabetes-self management education (DSME) is a cost-effective program that provides at-risk individuals with the knowledge and skills they need to adopt lifestyle changes that will improve their health and well-being. This systematic review examined the application of DSME in LMICs and identified the corresponding implementation results (cost, fidelity, acceptance, and adoption) associated with successful implementation in low-resource settings. Methods and analysis: The available research on T2D and the use of DSME in LMIC were systematically searched for using six electronic databases (PubMed, Embase, Cochrane, Web of Science, Google Scholar, PAIS, and EBSCO Discovery) between the months of October and November of 2022. The articles that met the search criteria were subsequently imported into EndNote and Covidence for analysis. The Cochrane RoB methodology for randomized trials was used to evaluate the risk of bias (RoB) in the included studies. A narrative synthesis was used to summarize the results. Results: A total of 773 studies were imported for screening, after 203 duplicates were removed, 570 remained. Abstract and title screenings resulted in the exclusion of 487 articles, leaving 83 for full-text review. Following a full-text review, 76 articles were excluded and seven were found to be relevant to our search. The most common reasons for exclusion were study design (n = 23), lack of results (n = 14), and wrong patient population (n = 12). Conclusion: Our systemic review found that DSME can be an acceptable and cost-effective solution in LMIC. While we intended to analyze cost, adoption, acceptability, and fidelity, our investigation revealed a gap in the literature on those areas, with most studies focusing on acceptability and cost and no studies identifying fidelity or adoption. To further evaluate the efficacy of DSME and enhance health outcomes for T2D in LMICs, more research is needed on its application. Systematic Review Registration: osf.io/7482t.

An Evolving HIV Epidemic in the Middle East and North Africa (MENA) Region: A Scoping Review.

Human immunodeficiency virus (HIV) in the Middle East and North Africa (MENA) region is severely understudied despite the region's increase in new HIV infections since 2010. A key population that is particularly affected, due to the lack of adequate knowledge and proper interventional implementation, includes people who inject drugs (PWID). Furthermore, the paucity of HIV data (prevalence and trends) worsens an already critical situation in this region. A scoping review was conducted to address the scarcity of information and to synthesize the available data on HIV prevalence rates within the key population of PWID throughout the MENA region. Information was sourced from major public health databases and world health reports. Of the 1864 articles screened, 40 studies discussed the various factors contributing to the under-reporting of HIV data in the MENA region among PWID. High and overlapping risk behaviors were cited as the most prevalent reason why HIV trends were incomprehensible and hard to characterize among PWID, followed by lack of service utilization, lack of intervention-based programs, cultural norms, lack of advanced HIV surveillance systems, and protracted humanitarian emergencies. Overall, the lack of reported information limits any adequate response to the growing and unknown HIV trends throughout the region.

Evidence-based interventions to reduce maternal malnutrition in low and middle-income countries: a systematic review.

Introduction: Despite remarkable strides in global efforts to reduce maternal mortality, low-and middle-income countries (LMICs) continue to grapple with a disproportionate burden of maternal mortality, with malnutrition emerging as a significant contributing factor to this enduring challenge. Shockingly, malnourished women face a mortality risk that is twice as high as their well-nourished counterparts, and a staggering 95% of maternal deaths in 2020 occurred within LMICs. The critical importance of addressing maternal malnutrition in resource-constrained settings cannot be overstated, as compelling research studies have demonstrated that such efforts could potentially save thousands of lives. However, the landscape is marred by a scarcity of evidence-based interventions (EBIs) specifically tailored for pregnant individuals aimed at combatting maternal malnutrition and reducing mortality rates. It is against this backdrop that our study endeavors to dissect the feasibility, adoption, sustainability, and cost-effectiveness of EBIs designed to combat maternal malnutrition. Methods: Our comprehensive search encompassed eight prominent databases covering the period from 2003 to 2022 in LMICs. We began our study with a comprehensive search across multiple databases, yielding a total of 149 studies. From this initial pool, we eliminated duplicate entries and the remaining studies underwent a thorough screening process resulting in the identification of 63 full-text articles that aligned with our predefined inclusion criteria. Results: The meticulous full-text review left us with a core selection of six articles that shed light on interventions primarily centered around supplementation. They underscored a critical issue -the limited understanding of effective implementation in these countries, primarily attributed to inadequate monitoring and evaluation of interventions and insufficient training of healthcare professionals. Moreover, our findings emphasize the pivotal role of contextual factors, such as cultural nuances, public trust in healthcare, the prevalence of misinformation, and concerns regarding potential adverse effects of interventions, which profoundly influence the successful implementation of these programs. Discussion: While the EBIs have shown promise in reducing maternal malnutrition, their true potential for feasibility, adoption, cost-effectiveness, and sustainability hinges on their integration into comprehensive programs addressing broader issues like food insecurity and the prevention of both communicable and non-communicable diseases.

Systematic review of end stage renal disease in Pakistan: Identifying implementation research outcomes.

AIM AND OBJECTIVES: The aim of this study was to conduct a systematic review analysis to identify and evaluate the available literature on implementation science outcomes research in relation to End Stage Renal Disease (ESRD) in Pakistan. METHODS: A systematic database search of PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and Ovid was conducted through October 22nd, 2022, without any restrictions on publication dates. A screening and data extraction tool, Covidence, was used to evaluate the literature against our inclusion and exclusion criteria. Furthermore, a Mixed Methods Appraisal Tool (MMAT) was used to evaluate the selected studies. RESULTS: We identified four studies that presented findings of implementation outcomes research which were related to appropriateness, feasibility, and acceptability. Appropriateness was examined using knowledge scores (p = 0.022) and medication adherence scores (p < 0.05) that showed statistical significance between the control and intervention groups. Acceptability was assessed through a cross sectional quantitative descriptive study that evaluated the reasons for refusal and acceptance of treatment in a cohort of patients suffering from ESRD. Feasibility was examined in one cross sectional, and one mixed methods study that aimed to evaluate and understand the impact of initiating dialysis treatment and the feasibility of maintaining it in low-income families that care for children or adults with ESRD. CONCLUSION: The preliminary results of this review indicate a gap in the availability of implementation research studies about ESRD in Pakistan. The burden of ESRD, and the implementation methods by which it is treated is notable in Pakistan and requires evidence-based measures to be implemented to support the critical healthcare delivery platforms that provide treatment.

Characterisation of medical conditions of children with sickle cell disease in the USA: findings from the 2007-2018 National Health Interview Survey (NHIS).

OBJECTIVES: We used the National Health Interview Survey (NHIS) data set to examine the prevalence of comorbid medical conditions; explore barriers to accessing healthcare and special educational services; and assess the associations between sickle cell disease (SCD) status and demographics/socioeconomic status (SES), and social determinants of health (SDoH) on comorbidities among children in the USA. DESIGN: Cross-sectional. SETTING: NHIS Sample Child Core questionnaire 2007-2018 data set. PARTICIPANTS: 133 481 children; presence of SCD was determined by an affirmative response from the adult or guardian of the child. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to compare the associations between SCD status, SES and SDoH for various medical conditions for all races and separately for black children at p<0.05. RESULTS: 133 481 children (mean age 8.5 years, SD: 0.02), 215 had SCD and ~82% (weighted) of the children with SCD are black. Children with SCD were more likely to suffer from comorbid conditions, that is, anaemia (adjusted OR: 27.1, p<0.001). Furthermore, children with SCD had at least two or more emergency room (ER) visits (p<0.001) and were more likely to have seen a doctor 1-15 times per year (p<0.05) compared with children without SCD. Household income (p<0.001) and maternal education were lower for children with SCD compared with children without SCD (52.4% vs 63.5% (p<0.05)). SCD children with a maternal parent who has < / > High School degree were less likely to have no ER visits or 4-5 ER visits, and more likely to have 2-3 ER visits within 12 months. CONCLUSION: Children with SCD experienced significant comorbid conditions and have high healthcare usage, with black children being disproportionately affected. Moreover, maternal education status and poverty level illustrates how impactful SES can be on healthcare seeking behaviour for the SCD population. SDoH have significant implications for managing paediatric patients with SCD in clinical settings.

A Review of the COVID-19 Mental Health Impact in Post-Conflict Settings: Bridging the Mental Health Gap with Case Exemplars from an Implementation Science Lens.

The COVID-19 pandemic has further aggravated the burden of mental health and presents an opportunity for public health research to focus on evidence-based interventions appropriate for populations residing in resource-constrained, post-conflict settings. Post-conflict settings have a higher service gap in mental health and fewer protective factors, such as economic and domestic security. Post-conflict settings are defined as locations where open warfare has ended but resulting challenges have remained for years. A strong emphasis on the engagement of diverse stakeholders is needed to arrive at sustainable and scalable solutions to mental health service delivery. This review discusses mental health service delivery gaps in post-conflict settings, highlights the urgency of the matter in the context of the COVID-19 pandemic, and provides recommendations for service gaps from evidence-based case study exemplars with an implementation science lens using the Consolidated Framework for Implementation Research (CFIR) as guide to improving adaptation and uptake.