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.

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.

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.

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.

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.

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.

Analysis of the 2007-2018 National Health Interview Survey (NHIS): Examining Neurological Complications among Children with Sickle Cell Disease in the United States.

This study compared neurological complications among a national sample of United States children with or without sickle cell disease (SCD) and evaluated health status, healthcare and special education utilization patterns, barriers to care, and association of SCD status and demographics/socioeconomic status (SES) on comorbidities and healthcare utilization. Data was acquired from the National Health Interview Survey (NHIS) Sample Child Core questionnaire 2007-2018 dataset that included 133,542 children. An affirmation from the guardian of the child determined the presence of SCD. Regression analysis was used to compare the associations between SCD and demographics/SES on neurological conditions at p < 0.05. Furthermore, adjusted odds ratios (AORs) were estimated for having various neurological conditions. Of the 133,481 children included in the NHIS, the mean age was 8.5 years (SD: 0.02) and 215 had SCD. Of the children with SCD, the sample composition included male (n = 110), and Black (n = 82%). The SCD sample had higher odds of having neuro-developmental conditions (p < 0.1). Families of Black children (55% weighted) reported household incomes < 100% of federal poverty level. Black children were more likely to experience longer wait times to see the doctor (AOR, 0.3; CI 0.1-1.1). Compared to children without SCD, those with SCD had a greater chance of seeing a medical specialist within 12 months (AOR 2.3; CI 1.5-3.7). This representative sample of US children with SCD shows higher odds of developing neurological complications, increased healthcare and special education services utilization, with Black children experiencing a disproportionate burden. This creates the urgency to address the health burden for children with SCD by implementing interventions in healthcare and increasing education assistance programs to combat neurocognitive impairments, especially among Black children.

Implementation outcomes and strategies for delivering evidence-based hypertension interventions in lower-middle-income countries: Evidence from a multi-country consortium for hypertension control.

Guidance on contextually tailored implementation strategies for the prevention, treatment, and control of hypertension is limited in lower-middle income countries (Lower-MIC). To address this limitation, we compiled implementation strategies and accompanying outcomes of evidence-based hypertension interventions currently being implemented in five Lower-MIC. The Global Research on Implementation and Translation Science (GRIT) Coordinating Center (CC) (GRIT-CC) engaged its global network sites at Ghana, Guatemala, India, Kenya, and Vietnam. Purposively sampled implementation science experts completed an electronic survey assessing implementation outcomes, in addition to implementation strategies used in their ongoing hypertension interventions from among 73 strategies within the Expert Recommendations for Implementing Change (ERIC). Experts rated the strategies based on highest priority to their interventions. We analyzed the data by sorting implementation strategies utilized by sites into one of the nine domains in ERIC and summarized the data using frequencies, proportions, and means. Seventeen implementation experts (52.9% men) participated in the exercise. Of Proctor's implementation outcomes identified across sites, all outcomes except for appropriateness were broadly assessed by three or more countries. Overall, 59 out of 73 (81%) strategies were being utilized in the five countries. The highest priority implementation strategies utilized across all five countries focused on evaluative and iterative strategies (e.g., identification of context specific barriers and facilitators) to delivery of patient- and community-level interventions, while the lowest priority was use of financial and infrastructure change strategies. More capacity building strategies (developing stakeholder interrelationships, training and educating stakeholders, and supporting clinicians) were incorporated into interventions implemented in India and Vietnam than Ghana, Kenya, and Guatemala. Although robust implementation strategies are being used in Lower -MICs, there is minimum use of financial and infrastructure change strategies. Our study contributes to the growing literature that demonstrates the use of Expert Recommendations for Implementing Change (ERIC) implementation strategies to deliver evidence-based hypertension interventions in Lower-MICs and will inform future cross-country data harmonization activities in resource-constrained settings.

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.

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.

Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Assessing descriptions of scalability for hypertension control interventions implemented in low-and middle-income countries: A systematic review.

BACKGROUND: The prevalence of hypertension continues to rise in low- and middle-income- countries (LMICs) where scalable, evidence-based interventions (EBIs) that are designed to reduce morbidity and mortality attributed to hypertension have yet to be fully adopted or disseminated. We sought to evaluate evidence from published randomized controlled trials using EBIs for hypertension control implemented in LMICs, and identify the WHO/ExpandNet scale-up components that are relevant for consideration during "scale-up" implementation planning. METHODS: Systematic review of RCTs reporting EBIs for hypertension control implemented in LMICs that stated "scale-up" or a variation of scale-up; using the following data sources PubMed/Medline, Web of Science Biosis Citation Index (BCI), CINAHL, EMBASE, Global Health, Google Scholar, PsycINFO; the grey literature and clinicaltrials.gov from inception through June 2021 without any restrictions on publication date. Two reviewers independently assessed studies for inclusion, conducted data extraction using the WHO/ExpandNet Scale-up components as a guide and assessed the risk of bias using the Cochrane risk-of-bias tool. We provide intervention characteristics for each EBI, BP results, and other relevant scale-up descriptions. MAIN RESULTS: Thirty-one RCTs were identified and reviewed. Studies reported clinically significant differences in BP, with 23 studies reporting statistically significant mean differences in BP (p < .05) following implementation. Only six studies provided descriptions that captured all of the nine WHO/ExpandNet components. Multi-component interventions, including drug therapy and health education, provided the most benefit to participants. The studies were yet to be scaled and we observed limited reporting on translation of the interventions into existing institutional policy (n = 11), cost-effectiveness analyses (n = 2), and sustainability measurements (n = 3). CONCLUSION: This study highlights the limited data on intervention scalability for hypertension control in LMICs and demonstrates the need for better scale-up metrics and processes for this setting. TRIAL REGISTRATION: Registration PROSPERO (CRD42019117750).

Toward a Theory of the Underpinnings and Vulnerabilities of Structural Racism: Looking Upstream from Disease Inequities among People Who Use Drugs.

Structural racism is increasingly recognized as a key driver of health inequities and other adverse outcomes. This paper focuses on structural racism as an "upstream" institutionalized process, how it creates health inequities and how structural racism persists in spite of generations of efforts to end it. So far, "downstream" efforts to reduce these health inequities have had little success in eliminating them. Here, we attempt to increase public health awareness of structural racism and its institutionalization and sociopolitical supports so that research and action can address them. This paper presents both a theoretic and an analytic approach to how structural racism contributes to disproportionate rates of HIV/AIDS and related diseases among oppressed populations. We first discuss differences in disease and health outcomes among people who use drugs (PWUD) and other groups at risk for HIV from different racial and ethnic populations. The paper then briefly analyzes the history of racism; how racial oppression, class, gender and other intersectional divisions interact to create health inequities; and how structural racism is institutionalized in ways that contribute to disease disparities among people who use drugs and other people. It examines the processes, institutions and other structures that reinforce structural racism, and how these, combined with processes that normalize racism, serve as barriers to efforts to counter and dismantle the structural racism that Black, indigenous and Latinx people have confronted for centuries. Finally, we discuss the implications of this analysis for public health research and action to undo racism and to enhance the health of populations who have suffered lifetimes of racial/ethnic oppression, with a focus on HIV/AIDS outcomes.

Development of the ASSESS tool: a comprehenSive tool to Support rEporting and critical appraiSal of qualitative, quantitative, and mixed methods implementation reSearch outcomes.

BACKGROUND: Several tools to improve reporting of implementation studies for evidence-based decision making have been created; however, no tool for critical appraisal of implementation outcomes exists. Researchers, practitioners, and policy makers lack tools to support the concurrent synthesis and critical assessment of outcomes for implementation research. Our objectives were to develop a comprehensive tool to (1) describe studies focused on implementation that use qualitative, quantitative, and/or mixed methodologies and (2) assess risk of bias of implementation outcomes. METHODS: A hybrid consensus-building approach combining Delphi Group and Nominal Group techniques (NGT) was modeled after comparative methodologies for developing health research reporting guidelines and critical appraisal tools. First, an online modified NGT occurred among a small expert panel (n = 5), consisting of literature review, item generation, round robin with clarification, application of the tool to various study types, voting, and discussion. This was followed by a larger e-consensus meeting and modified Delphi process with implementers and implementation scientists (n = 32). New elements and elements of various existing tools, frameworks, and taxonomies were combined to produce the ASSESS tool. RESULTS: The 24-item tool is applicable to a broad range of study designs employed in implementation science, including qualitative studies, randomized-control trials, non-randomized quantitative studies, and mixed methods studies. Two key features are a section for assessing bias of the implementation outcomes and sections for describing the implementation strategy and intervention implemented. An accompanying explanation and elaboration document that identifies and describes each of the items, explains the rationale, and provides examples of reporting and appraising practice, as well as templates to allow synthesis of extracted data across studies and an instructional video, has been prepared. CONCLUSIONS: The comprehensive, adaptable tool to support both reporting and critical appraisal of implementation science studies including quantitative, qualitative, and mixed methods assessment of intervention and implementation outcomes has been developed. This tool can be applied to a methodologically diverse and growing body of implementation science literature to support reviews or meta-analyses that inform evidence-based decision-making regarding processes and strategies for implementation.

Using a Syndemics Framework to Understand How Substance Use Contributes to Morbidity and Mortality among People Living with HIV in Africa: A Call to Action.

Substance use is increasing throughout Africa, with the prevalence of alcohol, tobacco, cannabis, and other substance use varying regionally. Concurrently, sub-Saharan Africa bears the world's largest HIV burden, with 71% of people living with HIV (PWH) living in Africa. Problematic alcohol, tobacco, and other substance use among PWH is associated with multiple vulnerabilities comprising complex behavioral, physiological, and psychological pathways that include high-risk behaviors (e.g., sexual risk-taking), HIV disease progression, and mental health problems, all of which contribute to nonadherence to antiretroviral therapy. Physiologically, severe substance use disorders are associated with increased levels of biological markers of inflammation; these, in turn, are linked to increased mortality among PWH. The biological mechanisms that underlie the increased risk of substance use among PWH remain unclear. Moreover, the biobehavioral mechanisms by which substance use contributes to adverse health outcomes are understudied in low- and middle-income countries (LMIC). Syndemic approaches to understanding the co-occurrence of substance use and HIV have largely been limited to high-income countries. We propose a syndemic coupling conceptual model to disentangle substance use from vulnerabilities to elucidate underlying disease risk for PWH. This interventionist perspective enables assessment of biobehavioral mechanisms and identifies malleable targets of intervention.

HIV, Tuberculosis, and Food Insecurity in Africa-A Syndemics-Based Scoping Review.

The double burden of HIV/AIDS and tuberculosis (TB), coupled with endemic and problematic food insecurity in Africa, can interact to negatively impact health outcomes, creating a syndemic. For people living with HIV/AIDS (PWH), food insecurity is a significant risk factor for acquiring TB due to the strong nutritional influences and co-occurring contextual barriers. We aim to synthesize evidence on the syndemic relationship between HIV/AIDS and TB co-infection and food insecurity in Africa. We conducted a scoping review of studies in Africa that included co-infected adults and children, with evidence of food insecurity, characterized by insufficient to lack of access to macronutrients. We sourced information from major public health databases. Qualitative, narrative analysis was used to synthesize the data. Of 1072 articles screened, 18 articles discussed the syndemic effect of HIV/AIDS and TB co-infection and food insecurity. Reporting of food insecurity was inconsistent, however, five studies estimated it using a validated scale. Food insecure co-infected adults had an average BMI of 16.5-18.5 kg/m2. Negative outcomes include death (n = 6 studies), depression (n = 1 study), treatment non-adherence, weight loss, wasting, opportunistic infections, TB-related lung diseases, lethargy. Food insecurity was a precursor to co-infection, especially with the onset/increased incidence of TB in PWH. Economic, social, and facility-level factors influenced the negative impact of food insecurity on the health of co-infected individuals. Nutritional support, economic relief, and psychosocial support minimized the harmful effects of food insecurity in HIV-TB populations. Interventions that tackle one or more components of a syndemic interaction can have beneficial effects on health outcomes and experiences of PWH with TB in Africa.

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.

The Role of Implementation Science in Advancing Resource Generation for Health Interventions in Low- and Middle-Income Countries.

Low- and middle-income countries (LMICs) bear the brunt of communicable and non-communicable diseases and experience higher mortality and poor health outcomes compared to resource-rich countries. Chronic resource deficits in LMICs impede their ability to successfully address vexing health issues. Implementation science provides researchers with an approach to develop specific interventions that can generate and/or maximize resources to facilitate the implementation of other public health interventions, in resource-constrained LMIC settings. Resources generated from these interventions could be in the form of increased health workers' skills, task shifting to free up higher-skilled health workers, increasing laboratory capacity, and using supply chain innovations to make medications available. Pivotal to the success of such interventions is ensuring feasibility in the LMIC context. We selected and appraised three case studies of evidence-based resource-generating health interventions based in LMICs (Zambia, Zimbabwe, and Madagascar), which generated or maximized resources to facilitate ongoing health services. We used a determinant implementation framework-Consolidated Framework for Implementation Research (CFIR) to identify and map contextual factors that are reported to influence implementation feasibility in an LMIC setting. Contextual factors influencing the feasibility of these interventions included leadership engagement, local capacity building and readiness for research and implementing evidence-based practices (EBPs), infrastructural support for multilevel scale-up, and cultural and contextual adaptations. These factors highlight the importance of utilizing implementation science frameworks to evaluate, guide, and execute feasible public health interventions and projects in resource-limited settings. Within LMICs, we recommend EBPs incorporate feasible resource-generating components in health interventions to ensure improved and sustained optimal health outcomes.

An Emerging Syndemic of Smoking and Cardiopulmonary Diseases in People Living with HIV in Africa.

BACKGROUND: African countries have the highest number of people living with HIV (PWH). The continent is home to 12% of the global population, but accounts for 71% of PWH globally. Antiretroviral therapy has played an important role in the reduction of the morbidity and mortality rates for HIV, which necessitates increased surveillance of the threats from pernicious risks to which PWH who live longer remain exposed. This includes cardiopulmonary comorbidities, which pose significant public health and economic challenges. A significant contributor to the cardiopulmonary comorbidities is tobacco smoking. Indeed, globally, PWH have a 2-4-fold higher utilization of tobacco compared to the general population, leading to endothelial dysfunction and atherogenesis that result in cardiopulmonary diseases, such as chronic obstructive pulmonary disease and coronary artery disease. In the context of PWH, we discuss (1) the current trends in cigarette smoking and (2) the lack of geographically relevant data on the cardiopulmonary conditions associated with smoking; we then review (3) the current evidence on chronic inflammation induced by smoking and the potential pathways for cardiopulmonary disease and (4) the multifactorial nature of the syndemic of smoking, HIV, and cardiopulmonary diseases. This commentary calls for a major, multi-setting cohort study using a syndemics framework to assess cardiopulmonary disease outcomes among PWH who smoke. CONCLUSION: We call for a parallel program of implementation research to promote the adoption of evidence-based interventions, which could improve health outcomes for PWH with cardiopulmonary diseases and address the health inequities experienced by PWH in African countries.