Implementation of fixed-dose combination therapy for secondary prevention of atherosclerotic cardiovascular disease among Syrian refugees in Lebanon: a qualitative evaluation.

BACKGROUND: We report findings of a qualitative evaluation of fixed-dose combination therapy for patients with established atherosclerotic cardiovascular disease (ASCVD) attending Médecins Sans Frontières (MSF) clinics in Lebanon. Cardiovascular disease is a leading cause of death and disability worldwide, and humanitarian actors are increasingly faced with the challenge of providing care for chronic diseases such as ASCVD in settings where health systems are disrupted. Secondary prevention strategies, involving 3-5 medications, are known to be effective for patients at risk of heart attack or stroke, but supply and adherence are challenging in humanitarian settings. Fixed dose combination therapy, combining two or more medications in one tablet, may be a strategy to address this. METHODS: The evaluation was nested within a prospective mixed-methods study in which eligible ASCVD patients were followed for 1 year during (i) 6 months of usual care then (ii) 6 months of fixed dose combination (FDC) therapy. After 1 year, we conducted in-depth interviews with a purposive sample of patients, MSF staff and external stakeholders. Interviews focused on acceptability and sustainability of the fixed dose therapy intervention. Interview data were analysed thematically, informed by thea Theoretical Framework of Acceptability. Additional attention was paid to non-typical cases in order to test and strengthen analysis. RESULTS: Patients and health care providers were positive about the FDC intervention. For patients, acceptability was related to ease of treatment and trust in MSF staff, while, for staff, it was related to perceived improvements in adherence, having a good understanding of the medication and its use, and fitting well with their priorities for patient's wellbeing. External stakeholders were less familiar with FDC therapy. While external clinicals expressed concerns about treatment inflexibility, non-clinician stakeholder interviews suggested that cost-effectiveness would have a major influence on FDC therapy acceptability. Sustainability was tied to the future role of MSF care provision and coherence with the local health system. CONCLUSIONS: For patients and clinic staff, FDC was an acceptable treatment approach for secondary prevention of ASCVD disease in two MSF clinics in Lebanon. Sustainability is more complex and calls for better alignment of care with public systems.

Development of a target product profile for a point-of-care cardiometabolic device.

INTRODUCTION: Multi-parameter diagnostic devices can simplify cardiometabolic disease diagnosis. However, existing devices may not be suitable for use in low-resource settings, where the burden of non-communicable diseases is high. Here we describe the development of a target product profile (TPP) for a point-of-care multi-parameter device for detection of biomarkers for cardiovascular disease and metabolic disorders, including diabetes, in primary care settings in low- and middle-income countries (LMICs). METHODS: A draft TPP developed by an expert group was reviewed through an online survey and semi-structured expert interviews to identify device characteristics requiring refinement. The draft TPP included 41 characteristics with minimal and optimal requirements; characteristics with an agreement level for either requirement of ≤ 85% in either the survey or among interviewees were further discussed by the expert group and amended as appropriate. RESULTS: Twenty people responded to the online survey and 18 experts participated in the interviews. Twenty-two characteristics had an agreement level of ≤ 85% in either the online survey or interviews. The final TPP defines the device as intended to be used for basic diagnosis and management of cardiometabolic disorders (lipids, glucose, HbA1c, and creatinine) as minimal requirement, and offering an expanded test menu for wider cardiometabolic disease management as optimal requirement. To be suitable, the device should be intended for level 1 healthcare settings or lower, used by minimally trained healthcare workers and allow testing using self-contained cartridges or strips without the need for additional reagents. Throughput should be one sample at a time in a single or multi-analyte cartridge, or optimally enable testing of several samples and analytes in parallel with random access. CONCLUSION: This TPP will inform developers of cardiometabolic multi-parameter devices for LMIC settings, and will support decision makers in the evaluation of existing and future devices.

Three Steps to Improve Management of Noncommunicable Diseases in Humanitarian Crises.

Kiran Jobanputra and colleagues argue that better evidence, guidance, and tools are needed to improve the effectiveness and feasibility of noncommunicable disease care in humanitarian settings.

Sodium stibogluconate and paromomycin for treating visceral leishmaniasis under routine conditions in eastern Sudan.

OBJECTIVES: Among patients with primary and relapse visceral leishmaniasis (VL) in eastern Sudan, we determined the proportion eligible for treatment with sodium stibogluconate and paromomycin (SSG/PM) and, of these, their demographic and clinical characteristics; initial treatment outcomes including adverse side effects requiring treatment discontinuation; treatment outcomes by 6 months; and risk factors associated with initial (slow responders) and late treatment failure (relapses and post-kala-azar dermal leishmaniasis, PKDL). METHODS: A retrospective cohort study in Tabarak Allah Hospital, Gedaref Province, eastern Sudan, from July 2011 to January 2014. RESULTS: Of 1252 individuals diagnosed with VL (1151 primary and 101 relapses), 65% were eligible for SSG/PM including 83% children, almost half of them malnourished and anaemic. About 4% of individuals discontinued treatment due to side effects; 0.7% died during treatment. Initial cure was achieved in 93% of 774 primary cases and 77% of 35 relapse cases (P < 0.001). Among the 809 patients eligible for SSG/PM, 218 (27%) were lost to follow-up. Outcomes by six months among the 591 patients with available follow-up data were: definitive cure (n = 506; 86%), relapse (n = 38; 6%), treatment discontinuation (n = 33; 6%), PKDL (n = 7; 1%) and death (n = 7; 1%). Among those completing a full course of SSG/PM, relapses and under-fives were at significantly higher risk of early and late treatment failure, respectively. CONCLUSION: Whether SSG/PM as a first-line regimen is an undeniable progress compared to SSG monotherapy, it excluded a considerable proportion of VL patients due to drug safety concerns. We call for accelerated development of new drugs and treatment regimens to improve VL treatment in Sudan.

Liposomal amphotericin B for complicated visceral leishmaniasis (kala-azar) in eastern Sudan: how effective is treatment for this neglected disease?

OBJECTIVES: The aim of this study was to report the patient profile and treatment outcomes, including relapses, of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (AmBisome) in Gedaref, Sudan. METHODS: AmBisome was offered to two groups of patients: primary VL patients with specific criteria (age ≤2 or ≥45 years, advanced clinical disease, pregnancy, HIV co-infection and contraindications for antimonials) and VL relapses. AmBisome was given at a total dose of 30 mg/kg, over 10 days. Slow responders received up to 50 mg/kg. Treatment failure was confirmed parasitologically. Standardised treatment outcomes were assessed. RESULTS: Between March 2010 and June 2012, a total of 281 (74%) patients with primary VL and 98 (26%) patients with VL relapses received AmBisome (54% male, median age = 11 years, interquartile range 2-30). End-of-treatment outcomes for primary VL were 260 (92%) initial cure including three (1%) slow responders, three (1%) treatment failures, 14 (5%) deaths and four (1%) unknown outcomes. Outcomes for VL relapses were 92 (94%) initial cure with five (5%) slow responders, four (4%) treatment failures, one (1%) death and one (1%) unknown outcome. At 6 months, there were 19 (7%) relapses amongst primary VL and 10 (10%) VL relapses had a new relapse. Loss to follow-up in both groups was 38%. None of the deaths that occurred during the study period was attributed to AmBisome. CONCLUSION: AmBisome appears to be effective for initial cure of VL and the drug seems safe, but is expensive (400 USD/treatment). Sustained mechanisms to allow improved access of this expensive drug particularly in East Africa are urgently needed. Relapses and losses to follow-up require specific investigation.

Fixed dose combination drugs for cardiovascular disease in a prolonged humanitarian crisis in Lebanon: an implementation study.

OBJECTIVES: This pre-post implementation study evaluated the introduction of fixed dose combination (FDC) medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention into routine care in a humanitarian setting. SETTING: Two Médecins sans Frontières (MSF) primary care clinics serving Syrian refugee and host populations in north Lebanon. PARTICIPANTS: Consenting patients ≥18 years with existing ASCVD requiring secondary prevention medication were eligible for study enrolment. Those with FDC contraindication(s) or planning to move were excluded. Of 521 enrolled patients, 460 (88.3%) were retained at 6 months, and 418 (80.2%) switched to FDC. Of these, 84% remained on FDC (n=351), 8.1% (n=34) discontinued and 7.9% (n=33) were lost to follow-up by month 12. INTERVENTIONS: Eligible patients, enrolled February-May 2019, were switched to Trinomia FDC (atorvastatin 20 mg, aspirin 100 mg, ramipril 2.5/5/10 mg) after 6 months' usual care. During the study, the COVID-19 pandemic, an economic crisis and clinic closures occurred. OUTCOME MEASURES: Descriptive and regression analyses compared key outcomes at 6 and 12 months: medication adherence, non-high density lipoprotein cholesterol (non-HDL-C) and systolic blood pressure (SBP) control. We performed per-protocol, intention-to-treat and secondary analyses of non-switchers. RESULTS: Among 385 switchers remaining at 12 months, total adherence improved 23%, from 63% (95% CI 58 to 68) at month 6, to 86% (95% CI 82 to 90) at month 12; mean non-HDL-C levels dropped 0.28 mmol/L (95% CI -0.38 to -0.18; p<0.0001), from 2.39 (95% CI 2.26 to 2.51) to 2.11 mmol/L (95% CI 2.00 to 2.22); mean SBP dropped 2.89 mm Hg (95% CI -4.49 to -1.28; p=0.0005) from 132.7 (95% CI 130.8 to 134.6) to 129.7 mm Hg (95% CI 127.9 to 131.5). Non-switchers had smaller improvements in adherence and clinical outcomes. CONCLUSION: Implementing an ASCVD secondary prevention FDC improved adherence and CVD risk factors in MSF clinics in Lebanon, with potential for wider implementation by humanitarian actors and host health systems.

Diabetes Care in Humanitarian Settings.

Despite the increasing prevalence of diabetes in populations experiencing humanitarian crisis, along with evidence that people living with diabetes are at higher risk for poor outcomes in a crisis, diabetes care is not routinely included in humanitarian health interventions. We here describe 4 factors that have contributed to the inequities and lack of diabetes inclusion in humanitarian programmes: (1) evolving paradigms in humanitarian health care, (2) complexities of diabetes service provision in humanitarian settings, (3) social and cultural challenges, and (4) lack of financing. We also outline opportunities and possible interventions to address these challenges and improve diabetes care among crisis-affected populations.

Using Clinical Vignettes to Understand the Complexity of Diagnosing Type 1 Diabetes in Sub-Saharan Africa.

Lack of awareness, access to insulin and diabetes care can result in high levels of morbidity and mortality for children with type 1 diabetes (T1DM) in sub-Saharan Africa (SSA). Improvements in access to insulin and diabetes management have improved outcomes in some settings. However, many people still present in diabetic ketoacidosis (DKA) in parallel to misdiagnosis of children with T1DM in contexts with high rates of communicable diseases. The aim of this study was to highlight the complexity of diagnosing pediatric T1DM in a healthcare environment dominated by infectious diseases and lack of adequate health system resources. This was done by developing clinical vignettes and recreating the hypothetico-deductive process of a clinician confronted with DKA in the absence of identification of pathognomonic elements of diabetes and with limited diagnostic tools. A non-systematic literature search for T1DM and DKA in SSA was conducted and used to construct clinical vignettes for children presenting in DKA. A broad differential diagnosis of the main conditions present in SSA was made, then used to construct a clinician's medical reasoning, and anticipate the results of different actions on the diagnostic process. An examination of the use of the digital based Integrated Management of Childhood Illness diagnostic algorithm was done, and an analysis of the software's efficiency in adequately diagnosing DKA was assessed. The main obstacles to diagnosis were low specificity of non-pathognomonic DKA symptoms and lack of tools to measure blood or urine glucose. Avenues for improvement include awareness of T1DM symptomatology in communities and health systems, and greater availability of diagnostic tests. Through this work clinical vignettes are shown to be a useful tool in analyzing the obstacles to underdiagnosis of diabetes, a technique that could be used for other pathologies in limited settings, for clinical teaching, research, and advocacy.

Heat-stability study of various insulin types in tropical temperature conditions: New insights towards improving diabetes care.

Strict storage recommendations for insulin are difficult to follow in hot tropical regions and even more challenging in conflict and humanitarian emergency settings, adding an extra burden to the management of people with diabetes. According to pharmacopeia unopened insulin vials must be stored in a refrigerator (2-8°C), while storage at ambient temperature (25-30°C) is usually permitted for the 4-week usage period during treatment. In the present work we address a critical question towards improving diabetes care in resource poor settings, namely whether insulin is stable and retains biological activity in tropical temperatures during a 4-week treatment period. To answer this question, temperature fluctuations were measured in Dagahaley refugee camp (Northern Kenya) using log tag recorders. Oscillating temperatures between 25 and 37°C were observed. Insulin heat stability was assessed under these specific temperatures which were precisely reproduced in the laboratory. Different commercialized formulations of insulin were quantified weekly by high performance liquid chromatography and the results showed perfect conformity to pharmacopeia guidelines, thus confirming stability over the assessment period (four weeks). Monitoring the 3D-structure of the tested insulin by circular dichroism confirmed that insulin monomer conformation did not undergo significant modifications. The measure of insulin efficiency on insulin receptor (IR) and Akt phosphorylation in hepatic cells indicated that insulin bioactivity of the samples stored at oscillating temperature during the usage period is identical to that of the samples maintained at 2-8°C. Taken together, these results indicate that insulin can be stored at such oscillating ambient temperatures for the usual four-week period of use. This enables the barrier of cold storage during use to be removed, thereby opening up the perspective for easier management of diabetes in humanitarian contexts and resource poor settings.

Challenges associated with providing diabetes care in humanitarian settings.

The humanitarian health landscape is gradually changing, partly as a result of the shift in global epidemiological trends and the rise of non-communicable diseases, including diabetes. Humanitarian actors are progressively incorporating care for diabetes into emergency medical response, but challenges abound. This Series paper discusses contemporary practical challenges associated with diabetes care in humanitarian contexts in low-income and middle-income countries, using the six building blocks of health systems described by WHO (information and research, service delivery, health workforce, medical products and technologies, governance, and financing) as a framework. Challenges include the scarcity of evidence on the management of diabetes and clinical guidelines adapted to humanitarian contexts; unavailability of core indicators for surveillance and monitoring systems; and restricted access to the medicines and diagnostics necessary for adequate clinical care. Policy and system frameworks do not routinely include diabetes and little funding is allocated for diabetes care in humanitarian crises. Humanitarian organisations are increasingly gaining experience delivering diabetes care, and interagency collaboration to coordinate, improve data collection, and analyse available programmes is in progress. However, the needs around all six WHO health system building blocks are immense, and much work needs to be done to improve diabetes care for crisis-affected populations.

Cardiovascular Disease among Syrian refugees: a descriptive study of patients in two Médecins Sans Frontières clinics in northern Lebanon.

BACKGROUND: Literature on the burden and management of atherosclerotic cardiovascular disease (ASCVD) in humanitarian settings is limited. This study aimed to describe patient characteristics and explore both service use and use of recommended secondary prevention drugs in Syrian refugee patients with ASCVD attending two Médecins Sans Frontières (MSF) clinics in Lebanon. METHODS: This study comprised a cross-sectional survey of ASCVD patients attending either MSF clinic over a four-week period in early 2017. Using descriptive statistics, we explored patient demographic characteristics, cardiovascular risk factors and assessed ASCVD secondary prevention medication prescription and patient adherence with a 7-day self-report scale. A retrospective study of routine clinical data explored workload and trends in patient loss to follow-up. We performed logistic regression modelling to explore risk factors for loss to follow-up. RESULTS: We included 514 patients with ASCVD in the cross-sectional study, performed in 2017. Most (61.9%) were male and mean age was 60.4 years (95% CI, 59.6-61.3). Over half (58.8%) underwent revascularization and 26.1% had known cerebrovascular disease. ASCVD risk factors included 51.8% with diabetes and 72.2% with hypertension. While prescription (75.7 to 98.2%) and self-reported adherence rates (78.4 to 93.9%) for individual ASCVD secondary prevention drugs (ACE-inhibitor, statin and antiplatelet) were high, the use of all three was low at 41.3% (CI95%: 37.0-45.6). The 5-year retrospective cohort study (ending April 2017) identified 1286 patients with ASCVD and 16,618 related consultations (comprising 24% of all NCD consultations). Over one third (39.7%) of patients were lost to follow-up, with lower risk among men. CONCLUSIONS: The burden of ASCVD within MSF clinics in Lebanon is substantial. Although prescription and adherence of individual secondary prevention drugs is acceptable, overall use of the three recommended drugs is suboptimal. Loss to follow-up rates were high. Further studies are needed to evaluate innovative strategies to increase the use of the multiple recommended drugs, and to increase the retention of patients with ASCVD in the care system.

The burden of diabetes and use of diabetes care in humanitarian crises in low-income and middle-income countries.

Human suffering as a result of natural disasters or conflict includes death and disability from non-communicable diseases, including diabetes, which have largely been neglected in humanitarian crises. The objectives of this Series paper were to examine the evidence on the burden of diabetes, use of health services, and access to care for people with diabetes among populations affected by humanitarian crises in low-income and middle-income countries, and to identify research gaps for future studies. We reviewed the scientific literature on this topic published between 1992 and 2018. The results emphasise that the burden of diabetes in humanitarian settings is not being captured, clinical guidance is insufficient, and diabetes is not being adequately addressed. Crisis-affected populations with diabetes face enormous constraints accessing care, mainly because of high medical costs. Further research is needed to characterise the epidemiology of diabetes in humanitarian settings and to develop simplified, cost-effective models of care to improve the delivery of diabetes care during humanitarian crises.

A cross-sectional assessment of diabetes self-management, education and support needs of Syrian refugee patients living with diabetes in Bekaa Valley Lebanon.

BACKGROUND: Patients with diabetes require knowledge and skills to self-manage their disease, a challenging aspect of treatment that is difficult to address in humanitarian settings. Due to the lack of literature and experience regarding diabetes self-management, education and support (DSMES) in refugee populations, Medecins Sans Frontieres (MSF) undertook a DSMES survey in a cohort of diabetes patients seen in their primary health care program in Lebanon. METHODS: Structured interviews were conducted with diabetes patients in three primary care clinics between January and February 2015. Scores (0-10) were calculated to measure diabetes core knowledge in each patient (the DSMES score). Awareness of long-term complications and educational preferences were also assessed. Analyses were conducted using Stata software, version 14.1 (StataCorp). Simple and multiple linear regression models were used to determine associations between various patient factors and the DSMES Score. RESULTS: A total of 292 patients were surveyed. Of these, 92% had type 2 diabetes and most (70%) had been diagnosed prior to the Syrian conflict. The mean DSMES score was 6/10. Having secondary education, previous diabetes education, a 'diabetes confidant', and insulin use were each associated with a higher DSMES Score. Lower scores were significantly more likely to be seen in participants with increasing age and in patients who were diagnosed during the Syrian conflict. Long-term complications of diabetes most commonly known by patients were vision related complications (68% of patients), foot ulcers (39%), and kidney failure (38%). When asked about the previous Ramadan, 56% of patients stated that they undertook a full fast, including patients with type 1 diabetes. Individual and group lessons were preferred by more patients than written, SMS, telephone or internet-based educational delivery models. CONCLUSIONS: DSMES should be patient and context appropriate. The variety and complexities of humanitarian settings provide particular challenges to its appropriate provision. Understanding patient baseline DSMES levels and needs provides a useful basis for humanitarian organizations seeking to provide diabetes care.