Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies.

In the rapidly evolving landscape of biotechnologies, cell and gene therapies are being developed and adopted at an unprecedented pace. However, their access and adoption remain limited, particularly in low- and middle-income countries (LMICs). This study aims to address this critical gap by exploring the potential of applying a hub and spoke model for cell and gene therapy delivery in LMICs. We establish the identity and roles of relevant stakeholders, propose a hub and spoke model for cell and gene therapy delivery, and simulate its application in Brazil and the Middle East and North Africa. The development and simulation of this model were informed by a comprehensive review of academic articles, grey literature, relevant websites, and publicly available data sets. The proposed hub and spoke model is expected to expand availability of and access to cell and gene therapy in LMICs and presents a comprehensive framework for the roles of core stakeholders, laying the groundwork for more equitable access to these lifesaving therapies. More research is needed to explore the practical adoption and implications of this model.

Maternal health outcomes in the context of fragility: a retrospective study from Lebanon.

BACKGROUND AND AIMS: The Lebanese healthcare system faces multiple challenges including limited capacities, shortage of skilled professionals, and inadequate supplies, in addition to hosting a significant number of refugees. While subsidized services are available for pregnant women, representing the majority of the refugee population in Lebanon, suboptimal access to antenatal care (ANC) and increased maternal mortality rates are still observed, especially among socioeconomically disadvantaged populations. This study aimed to review the maternal health outcomes of disadvantaged Lebanese and refugee pregnant women seeking ANC services at primary healthcare centers (PHCs) in Lebanon. METHODS: A retrospective chart review was conducted at twenty PHCs in Lebanon, including Ministry of Public Health (MOPH) and United Nations Relief and Works Agency for Palestine refugees (UNRWA) facilities. Data was collected from medical charts of pregnant women who visited the centers between August 2018 and August 2020. Statistical analysis was performed to explore outcomes such as the number of ANC visits, delivery type, and onset of delivery, using bivariate and multivariable logistic regression models. RESULTS: In the study, 3977 medical charts were analyzed. A multivariate logistic regression analysis, revealed that suboptimal ANC visits were more common in the Beqaa region and among women with current abortion or C-section. Syrians had reduced odds of C-sections, and Beqaa, Mount Lebanon, and South Lebanon regions had reduced odds of abortion. Suboptimal ANC visits and history of C-section increased the odds of C-section and abortion in the current pregnancy. As for preterm onset, the study showed an increased likelihood for it to occur when being Palestinian, having current C-section delivery, experiencing previous preterm onset, and enduring complications at the time of delivery. CONCLUSION: This study suggests the need for low-cost interventions aiming at enhancing access to ANC services, especially among pregnant women in fragile settings.

Evaluating a research training programme for frontline health workers in conflict-affected and fragile settings in the middle east.

BACKGROUND: Health Research Capacity Building (HRCB) is key to improving research production among health workers in LMICs to inform related policies and reduce health disparities in conflict settings. However, few HRCB programmes are available in the MENA region, and few evaluations of HRCB globally are reported in the literature. METHODS: Through a qualitative longitudinal design, we evaluated the first implementation of the Center for Research and Education in the Ecology of War (CREEW) fellowship. Semi-structured interviews were conducted with fellows (n = 5) throughout the programme at key phases during their completion of courses and at each research phase. Additional data was collected from supervisors and peers of fellows at their organizations. Data were analysed using qualitative content analysis and presented under pre-identified themes. RESULTS: Despite the success of most fellows in learning on how to conduct research on AMR in conflict settings and completing the fellowship by producing research outputs, important challenges were identified. Results are categorized under predefined categories of (1) course delivery, (2) proposal development, (3) IRB application, (4) data collection, (5) data analysis, (6) manuscript write-up, (7) long-term effects, and (8) mentorship and networking. CONCLUSION: The CREEW model, based on this evaluation, shows potential to be replicable and scalable to other contexts and other health-related topics. Detailed discussion and analysis are presented in the manuscript and synthesized recommendations are highlighted for future programmes to consider during the design, implementation, and evaluation of such programmes.

Reproductive health of Syrian refugee women in Lebanon: a descriptive analysis of the Sijilli electronic health records database.

BACKGROUND: The Syrian conflict has been responsible for the highest exodus of refugees, with Lebanon hosting the greatest number of refugees per capita, which placed a significant strain on an already overburdened healthcare system. Women are the most vulnerable group in times of conflict and displacement, with sexual and reproductive health and rights often neglected. This study focuses on the obstetric characteristics and pregnancy outcomes of Syrian Refugee (SR) women in Lebanon, in Comparison to their pre-displacement data. METHODS: This study is a secondary analysis of de-identified data from the Sijilli database. The data reported and analyzed were the refugees' socio-demographics, obstetric history, pregnancy outcomes, experienced maternal and neonatal complications, breastfeeding history and duration, and contraception use and types. Data were reported in both frequencies and means/medians. Chi-square test, t-test, and ANOVA tests were used to compare pregnancies in Syria to those that happened in Lebanon. RESULTS: A total of 1065 female records were included in this study, with 634 ever-pregnant women and the total number of pregnancies being 3272. SR women were shown to get pregnant in Lebanon at a younger age compared to cases in Syria. The number of gravidities is equal in women who got pregnant in Syria and those who moved later to Lebanon. The mean spacing between pregnancies has decreased comparing SR women who got pregnant in Syria only versus those who got pregnant in Lebanon only. Among the mixed group, the mean spacing between pregnancies as well as the prevalence of spontaneous abortions significantly increased after displacing to Lebanon. C-section rate was higher among SR women after moving to Lebanon. Also, maternal complications and not breastfeeding have increased after moving to Lebanon. A prior pregnancy was significantly associated with higher contraception use rate. The most common methods of contraception were oral contraceptive pills and intra-uterine devices. CONCLUSION: The C-section deliveries, spontaneous abortions and maternal complications have all increased among SR women after being displaced to Lebanon. While the age at first pregnancy, mean spacing between their pregnancies and breastfeeding rates have decreased after moving to Lebanon. SR women are less likely to use contraceptives after their displacement. It is necessary to address access to reproductive healthcare and antenatal care delivery among displaced refugee women living in informal tented settlements.

Genuine policy learning is fundamental: the journey of the United Arab Emirates toward the establishment of health technology assessment.

The launch of innovative technologies has been credited with significant improvements in health indicators, but it comes at a high financial impact, and the value of certain innovations may not be well documented. Health technology assessment (HTA) is a universally established process to assess the incremental value of innovations. Despite its acknowledged value, almost one-third of the countries around the globe have not established yet a formal HTA in their health systems. The UAE is one of the pioneering countries worldwide in adopting innovative health technologies. This emphasizes the importance of exploring the key elements in the UAE's journey toward the establishment of HTA. Our study aims to articulate an academic insight that can support the ongoing endeavors to establish the HTA in the UAE. This case study was guided by an analytical framework. Data was collected from document review and semistructured interviews, then analyzed by applying the codebook thematic analysis technique. The findings outline multiple facilitators and challenges in the perspective process, as they show a multidimensional interlink between all identified elements. Markedly, leveraging the role of specialized academia and building HTA genuine knowledge are the areas that need the most attention. The originality of this research is associated with analyzing the three health policy pillars: the context, actors, and content in a prospective HTA establishment process. The main practical implications generated from this study are supporting global health organizations, HTA policy entrepreneurs, and academics in improving their strategies and designing more effective HTA policy learning programs.

Ulnar Superficialis Slip Resection Versus Radial Superficialis Slip Resection: A Biomechanical Pilot Study.

BACKGROUND: There are numerous clinical scenarios during which the surgeon contemplates whether the radial or ulnar slip of the flexor digitorum superficialis (FDS) should be sacrificed. To date no study has assessed the point of failure of each one of the FDS slips in each digit, aiding the avid surgeon in deciding which slip to sacrifice. METHODS: A total of 41 digits were assessed, each digit was dissected, and a specimen containing the denuded bone of the middle phalanx with the attachments of the ulnar and radial FDS slips was obtained. An Instron 4502 device was utilized to biomechanically assess the point of failure of each slip of each digit. RESULTS: There was no statistical difference between ulnar and radial slip point of failure when compared across all digits and subjects. There was no statistical difference between male and female subject's specimens. The point of failure was higher in the ulnar slips of the second and third digits, whereas the point of failure was higher in the radial slips of the fourth and fifth digits. CONCLUSIONS: Sacrifice of a FDS slip may cause loss of grip strength. In several clinical scenarios one may be faced with the dilemma which FDS slip to sacrifice. Our findings show this is not an arbitrary choice. Hand surgeons should keep our findings in mind when deciding which slip to sacrifice, in effort to preserve function and strength in the injured hand.

Cancer registration in the Middle East, North Africa, and Turkey (MENAT) region: A tale of conflict, challenges, and opportunities.

Cancer registration is a core component of national and regional cancer control strategies. In the Middle East, North-Africa and Turkey (MENAT) region, capacity and resources for cancer registration is variable and shaped by multiple contextual challenges. This viewpoint maps out practical recommendations around cancer registration, in an attempt to inform cancer control planning, policy, and implementation. The recommendations laid out in this viewpoint are informed by the discussions held at the Initiative for Cancer Registration in the MENAT (ICRIM) virtual workshop, which convened registry managers, policy makers, and international agencies from 19 countries in the MENAT region. The discussions were distilled in four categories of recommendations, revolving around cancer registration procedures, collaborative governance, putting cancer registration on the map, and capacity building. This viewpoint provides a much-needed mapping of practical recommendations around cancer registration, informed by direct key stakeholders in the region. These practical recommendations offer a road map for policy making, cancer control planning, and future regional capacity strengthening initiatives.

[DE QUERVAIN'S TENOSYNOVITIS - CLINICAL PRESENTATION AND TREATMENT].

INTRODUCTION: De-Quervain tenosynovitis, named after the Swiss surgeon Fritz De Quervain, is a condition characterized by pain and tenderness over the first extensor compartment of the wrist. This compartment contains the extensor pollicis brevis (EPB) and abductor pollicis longus (APL) tendons in their individual retinacular sheath. Non-inflammatory thickening of the tendinous sheath leads to entrapment of the individual tendons and increased friction. The condition is more common in women, particularly aged 30-50 years old and those 4-6 weeks in their post-partum period. It can be associated with trauma or repetitive motion but is typically of unknown etiology. While most cases are self-limiting, treatment is often required and comprises of non-operative treatment: anti-inflammatory medication, wrist splints and local steroid injection; and operative treatment: surgical release of the 1st dorsal compartment.

[MULTIPLE GIANT CELL TUMOR OF TENDON SHEATH: A CASE REPORT OF THREE LESIONS ON THE SAME FLEXOR TENDON].

INTRODUCTION: We present a case report of a triple location Giant Cell Tumor of tendon sheath appearance on the same flexor tendon sheath of a single digit. There have been scarce descriptions of multiple Giant Cell Tumors of tendon sheath. Multiple tumors may predispose patients to a higher recurrence rate; therefore, recognition and treatment of this rare entity is important.

[MEDIAL EPICONDYLITIS (GOLFER'S ELBOW) - CLINICAL PRESENTATION AND TREATMENT].

INTRODUCTION: Medial epicondylitis, which is also called "Golfer's Elbow" is a pathology which typically presents as medial elbow pain. It affects 1% of the general population, yet affects 3.8% to 8.2% of work-related complaints. Golfer's elbow is common in the 40 to 60-year-old age group so those suffering from it are part of the workforce and hence, its economic impact. Women and men alike suffer from golfer's elbow, and microtrauma combined with attritional changes in the common flexor tendon origin at the medial aspect of the elbow are the culprit of this pathology. The first line of treatment is conservative therapy and only when it fails is an open surgical approach utilized. New approaches to treating this ailment such as use of Extra Corporeal Shock Wave therapy and the use of injectable blood derivatives, as well as new surgical techniques are also being applied.

The determinants of the quality of clinical management among diabetic and hypertensive patients in a context of fragility: A cross-sectional survey from Lebanon.

Introduction: The management of NCDs is a growing challenge in low- and middle-income settings with the increasing prevalence and the associated demands that such conditions make on health systems. Fragile settings both exacerbate the risk of NCDs and undermine systems capacity. Lebanon is a setting where strategies to address rising NCDs burden have faced particularly acute contextual challenges. Methods: We conducted a cross-sectional survey with patients accessing non-communicable disease across 11 primary care centers within the Greater Beirut and Beqaa areas. Response were received from 1,700 patients. We generated a Clinical Management Index Score as a measure of quality of care, and scores related to a range of socio-demographic characteristics and other context specific variables. Results: Significantly higher clinical management index scores (better quality of care) were associated with patients living in the semi-urban/rural context of Beqaa (compared to Greater Beirut), having health insurance coverage, aged above 60, having high levels of educational attainment, and making partial or full payment for their treatment. Relatively lower index scores (poorer quality of care) were associated with Syrian nationality (compared to Lebanese) and with patients suffering from diabetes or hypertension (compared to comorbid patients). Conclusion: The study identified a wide margin for improving quality of NCDs care in fragile contexts with particular gaps identified in referral to ophthalmology, accessing all prescribed medication and receiving counseling for smoking cessation. Additionally, findings indicate a number of predictors of comparatively poor quality of care that warrant attention, notably with regard to Syrian nationality/legal status, lack of health coverage, seeking free health provision and lower educational attachment. Although these are all relevant risk factors, the findings call on donor agencies, NGOs and provider institutions to design targeted programs and activities that especially ensure equitable delivery of services to diabetic and hypertensive patients with compounded vulnerability as a result of a number of these factors.

[ACUTE INJURY TO FLEXOR TENDONS OF THE HAND: ASSESSMENT, DIAGNOSIS AND TREATMENT].

INTRODUCTION: Hand lacerations are common injuries seen by the primary care physician. Even seemingly small cuts carry a high risk of injury to flexor tendons of the hand which requires surgical treatment by a specialist. Elucidation of the relevant history, along with a dedicated and focused physical examination is imperative for an early intervention which, along with a meticulous surgical technique and dedicated rehabilitation by occupational therapists, will lead to a much improved functional prognosis for the patient. This is a brief review of the anatomy and physiology of flexor tendons injury and repair, with historical milestones of developments in the approach to the injury. The article also highlights the surgical procedure brought forth by the late Professor Isidor Kessler, one of the founders of surgery of the hand in Israel, presented here as an overview and guidance to the primary care physician.

Assessing innovative approaches for global health capacity building in fragile settings in the MENA region: development of the evaluation of capacity building (eCAP) program.

BACKGROUND: Given the magnitude and frequency of conflicts in the MENA region along with their devastating impact on health responses and outcomes, there exists a strong need to invest in contextualized, innovative, and accessible capacity building approaches to enhance leadership and skills in global health. The MENA region suffers from limited (1) continued educational and career progression opportunities, (2) gender balance, and (3) skill-mix among its health workforce, which require significant attention. MAIN TEXT: The Global Health Institute at the American University of Beirut incepted the Academy division to develop and implement various global health capacity building (GHCB) initiatives to address those challenges in fragile settings across low-and middle-income countries in the MENA region. These initiatives play a strategic role in this context, especially given their focus on being accessible through employing innovative learning modalities. However, there exists a dearth of evidence-based knowledge on best practices and recommendations to optimize the design, implementation, and evaluation of GHCB in fragile settings in the MENA region. The present paper describes the development of the evaluation of capacity building program (eCAP), implemented under the Academy division, to assess the effectiveness of its initiatives. eCAP is composed of 3 phases: (1) a situational assessment, followed by (2) production of multiple case studies, and finally (3) a meta-assessment leading to model development. The goal of eCAP is not only to inform the Academy's operations, but also to synthesize produced knowledge into the formation of an evidence-based, scalable, and replicable model for GHCB in fragile settings. CONCLUSION: eCAP is an important initiative for researchers, educators, and practitioners interested in GHCB in fragile settings. Several lessons can be learned from the outcomes it has yielded so far in its first two phases of implementation, ranging from the situational assessment to the production of evaluation case studies, which are expanded on in the manuscript along with pertinent challenges.

Outpatient use patterns and experiences among diabetic and hypertensive patients in fragile settings: a cross-sectional study from Lebanon.

OBJECTIVES: Assess and describe the health service use and delivery patterns for non-communicable disease (NCD) services in two contrasting fragility contexts and by other principal equity-related characteristics including gender, nationality and health coverage. SETTING: Primary healthcare centres located in the urbanised area of Greater Beirut and the rural area of the Beqaa Valley. DESIGN: This is a cross-sectional study using a structured survey tool between January and September 2020. PARTICIPANTS: 1700 Lebanese and Syrian refugee patients seeking primary care for hypertension and diabetes. PRIMARY AND SECONDARY OUTCOMES: The main outcome is the comprehensiveness of service delivery comparing differences in use and service delivery patterns by fragility setting, gender, nationality and health coverage. RESULTS: Compliance with routine NCD care management (eg, counselling, immunisations, diagnostic testing and referral rates) was significantly better in Beirut compared with Beqaa. Women were significantly less likely to be offered lifestyle counselling advice and referral to cardiologists (58.4% vs 68.3% in Beqaa and 58.1% vs 62% in Beirut) and ophthalmologists, compared with men. Across both settings, there was a significant trend for Lebanese patients to receive more services and more advice related to nutrition and diabetes management (89.8% vs 85.2% and 62.4% vs 55.5%, respectively). Similarly, referral rates were higher among Lebanese refugees compared with Syrian refugees. Immunisation and diagnostic testing were significantly higher in Beirut among those who have health coverage compared with Beqaa. CONCLUSIONS: The study discovered significant differences in outpatient service use by setting, nationality and gender to differentials. A rigorous and comprehensive appraisal of NCD programmes and services is imperative for providing policy makers with evidence-based recommendations to guide the design, implementation and evaluation of targeted programmes and services necessary to ensure equity in health services delivery to diabetic and hypertensive patients. Such programmes are an ethical imperative considering the protracted crises and compounded fragility.

Evaluating an e-learning program to strengthen the capacity of humanitarian workers in the MENA region: the Humanitarian Leadership Diploma.

BACKGROUND: The Middle East and North Africa (MENA) region is consistently plagued with humanitarian crises while having little response capacity. Despite their obvious growing need, there exist limited educational opportunities for humanitarian workers to develop their capacity in humanitarian topics. The present study evaluates an online training program, the Humanitarian Leadership Diploma (HLD), which targeted humanitarian workers across the MENA region. METHODS: A mixed-methods design was used, comprising short and long-term quantitative and qualitative data, targeting individual and organizational-level outcomes. A total of 28 humanitarian workers across the MENA region enrolled in the program starting September 2019 until October 2020, 18 of which completed the full diploma. Short-term quantitative data such as knowledge assessments, course evaluations, and reflective commentaries were collected from all learners, whereas long-term qualitative data was collected only from those who completed the full diploma and from peers at their organizations, 6 months after completion. Data was triangulated, analyzed using qualitative content analysis, and reported as themes. RESULTS: The program was overall successful given multiple factors reported by participants such as enhanced knowledge, high satisfaction, and improved practice, with some important challenges being identified. Themes under the strengths category related to (1) online learning, (2) significance of diploma, (3) course content, (4) instructors, (5) transfer of learning into practice, and (6) personal development. Themes under the challenges category related to (1) barriers to applying changes in behavior and performance, (2) engagement and interaction, and (3) pedagogical approach. CONCLUSION: This is one of very few evaluations of locally developed and delivered online learning programs for humanitarian actors in the MENA region. The findings are especially important as they may inform researchers and humanitarian actors looking to design and deliver similar programs in the MENA region or other fragile settings. Key recommendations are discussed in the manuscript, and include to combine synchronous and asynchronous approaches, design concise course materials, limit theoretical pedagogical approaches, ensure topics are contextualized to the region, and consider continuous engagement strategies for learners.

COVID-19: Marking the Gaps in Migrant and Refugee Health in Some Massive Migration Areas.

The health of migrants and refugees, which has long been a cause for concern, has come under greatly increased pressure in the last decade. Against a background where the world has witnessed the largest numbers of migrants in history, the advent of the COVID-19 pandemic has stretched the capacities of countries and of aid, health and relief organizations, from global to local levels, to meet the human rights and pressing needs of migrants and refugees for access to health care and to public health measures needed to protect them from the pandemic. The overview in this article of the situation in examples of middle-income countries that have hosted mass migration in recent years has drawn on information from summaries presented in an M8 Alliance Expert Meeting, from peer-reviewed literature and from reports from international agencies concerned with the status and health of migrants and refugees. The multi-factor approach developed here draws on perspectives from structural factors (including rights, governance, policies and practices), health determinants (including economic, environmental, social and political, as well as migration itself as a determinant) and the human security framework (defined as "freedom from want and fear and freedom to live in dignity" and incorporating the interactive dimensions of health, food, environmental, economic, personal, community and political security). These integrate as a multi-component 'ecological perspective' to examine the legal status, health rights and access to health care and other services of migrants and refugees, to mark gap areas and to consider the implications for improving health security both for them and for the communities in countries in which they reside or through which they transit.