Liver Injury Following Isoniazid Preventive Therapy in HIV Patients Attending Halibet National Referral Hospital, Eritrea: A Prospective Cohort Study.

INTRODUCTION: A 6-month course of isoniazid, 300 mg daily, was programmatically introduced in Eritrea in 2014 as tuberculosis preventive therapy in people living with human immunodeficiency virus (PLHIV). The rollout of isoniazid preventive therapy (IPT) in PLHIV was successful in the first 2-3 years. After 2016, rumours based on rare but real incidents of liver injuries following use of IPT spread widely across the country and created concerns amongst healthcare professionals and consumers, that ultimately caused dramatic decline in the rollout of the intervention. Decision makers have been demanding better evidence as previously conducted local studies had inherent methodological limitations. This real-world observational study was conducted to evaluate the risk of liver injury associated with IPT among PLHIV attending Halibet national referral hospital, Asmara, Eritrea. METHODS: A prospective cohort study, that consecutively enrolled PLHIV attending Halibet hospital, was conducted between 1 March and 30 October 2021. Those exposed to anti-retroviral therapy (ART) plus IPT were considered as exposed and those taking only ART were considered as unexposed. Both groups were prospectively followed up for 4-5 months with monthly liver function tests (LFTs). A Cox proportional hazard model was used to explore whether there was increased risk of drug-induced liver injury (DILI) associated with IPT. Probability of survival without DILI was also estimated using Kaplan-Meier curves. RESULTS: A total of 552 patients, 284 exposed and 268 unexposed, completed the study, with a mean follow-up time of 3.97 (SD 0.675) months for the exposed and 4.06 (SD 0.675) months for the unexposed. Twelve patients developed drug-induced liver injury (DILI), with a median time-to-onset of 35 days (interquartile range: 26.8, 60 days). All cases were from the exposed group and all except two cases were asymptomatic. The incidence rate of DILI in the exposed group was 10.6 cases per 1000 person-months and zero for the unexposed group (p = 0.002). CONCLUSION: DILI in PLHIV taking IPT was common; therefore, liver function should be closely monitored to safely administer the product. Despite high levels of deranged liver enzymes, the majority had no symptoms of DILI, emphasising the importance of close laboratory monitoring, especially during the first 3 months of treatment.

Perspectives of Healthcare Professionals on Factors Limiting Implementation of Isoniazid Preventive Therapy in People Living with HIV in Eritrea: A Qualitative Study.

Purpose: In Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals. Materials and Methods: An exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis. Results: Overall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems. Conclusion: The root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.

Use of unstructured text in prognostic clinical prediction models: a systematic review.

OBJECTIVE: This systematic review aims to assess how information from unstructured text is used to develop and validate clinical prognostic prediction models. We summarize the prediction problems and methodological landscape and determine whether using text data in addition to more commonly used structured data improves the prediction performance. MATERIALS AND METHODS: We searched Embase, MEDLINE, Web of Science, and Google Scholar to identify studies that developed prognostic prediction models using information extracted from unstructured text in a data-driven manner, published in the period from January 2005 to March 2021. Data items were extracted, analyzed, and a meta-analysis of the model performance was carried out to assess the added value of text to structured-data models. RESULTS: We identified 126 studies that described 145 clinical prediction problems. Combining text and structured data improved model performance, compared with using only text or only structured data. In these studies, a wide variety of dense and sparse numeric text representations were combined with both deep learning and more traditional machine learning methods. External validation, public availability, and attention for the explainability of the developed models were limited. CONCLUSION: The use of unstructured text in the development of prognostic prediction models has been found beneficial in addition to structured data in most studies. The text data are source of valuable information for prediction model development and should not be neglected. We suggest a future focus on explainability and external validation of the developed models, promoting robust and trustworthy prediction models in clinical practice.

Effectiveness of a 6-Month Isoniazid on Prevention of Incident Tuberculosis Among People Living with HIV in Eritrea: A Retrospective Cohort Study.

INTRODUCTION: A 6-month isoniazid as tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) was nationally introduced in Eritrea in 2014. However, its effectiveness in preventing tuberculosis (TB) and duration of protection was questioned by physicians. This study was, therefore, conducted to evaluate the impact of the isoniazid preventive therapy (IPT) primarily on the prevention of TB and duration of its protection in PLHIV. METHODS: A retrospective cohort study was conducted that selected all eligible PLHIV attending HIV care clinics in all national and regional referral hospitals in Eritrea. Data was collected from patients' clinical cards using a structured data extraction sheet. The association between use of IPT and outcomes of interest was assessed using a Cox proportional hazard regression model and Kaplan-Meier curve. RESULTS: A total of 6803 patients were selected, which accounted for 75% of all PLHIV-accessing HIV care clinics in Eritrea. About 76% of patients were exposed to IPT while the remaining 24% were unexposed. The mean follow-up time was 4.9 years (SD 1.4). The incidence rate of TB was 1.7 and 10 cases per 1000 person-years in the exposed and unexposed, respectively. The unexposed had a higher risk of incident TB (adjusted hazard ratio [aHR] 3.75, 95% confidence interval [CI] 2.89, 6.13) and all-cause mortality (HR 2.41, 95% CI 1.85, 3.14) compared to the exposed. A Kaplan-Meier curve showed that the exposed group had a higher TB-free follow-up probability (98.8%) compared to the unexposed (95%) at 65 months of follow-up (p < 0.001). IPT protection decreased rapidly 6 months after isoniazid completion. CONCLUSION: Use of a 6-month isoniazid as TPT was found to be effective in reducing incident TB in PLHIV-accessing HIV care clinics in Eritrea. However, the protection appeared to diminish soon, namely 6 months after completion of isoniazid, which warrants immediate attention from policy makers.

An assessment of the quality of care provided at primary health care centres in camps for internally displaced persons in Iraq in 2018.

INTRODUCTION: The humanitarian crisis in Iraq remains one of the largest and most unstable in the world. In 2014, over 2.5 million civilians were displaced in Iraq; between 2015 and 2017 more than 3 million people continued to be displaced. While health-related research concerning internally displaced persons (IDPs) population has been conducted in many settings, very few have looked at the quality of care delivered in primary health care centres (PHCC) inside camps. The objective of this operational research is to assess the quality of health care services at PHCC in operational IDP camps supported by local and international NGOs (humanitarian partners) as well as the Directorate of Health (DoH) in Iraq at baseline and after 6 months. METHOD: A framework based on five components was used to assess quality of care by assigning a quality-of-care index score. Using a longitudinal design; data were collected through observations of facilities and of patient consultations, as well as health worker and patient exit interviews, in static PHCC in operational IDP camps of Iraq during two different phases: in June (n = 55), and December 2018 (n = 47). These facilities supported more than 500,000 IDPs. Descriptive and statistical analyses were conducted, and the results compared. RESULT: For all camps (n = 47), the average overall quality of care index score increased between the two phases. No specific type of organisation consistently provided a better quality of care. The camp size was unrelated to the quality of care provided at the respective facility. The domain indicators "Client Care" and "Environment and Safety" mostly related to the variation in the general assessment of quality. Patient satisfaction was unrelated to any other domain score. Compared at 0 and after 6-months, the quality of care index score between the type of organisation and governorate showed that feedback positively impacted service delivery after the first assessment. Positive differences in scores also appeared, with notable improvements in Client care and Technical competence. CONCLUSION: Humanitarian partners and the DoH are able to provide quality care, independent of camp size or the number of camps managed, and their cooperation can lead to quick improvements. This research also shows that quality of care assessment in emergency settings can be carried out in formal IDP camps using non-emergency standards.

Bridging research integrity and global health epidemiology (BRIDGE) statement: guidelines for good epidemiological practice.

BACKGROUND: Research integrity and research fairness have gained considerable momentum in the past decade and have direct implications for global health epidemiology. Research integrity and research fairness principles should be equally nurtured to produce high-quality impactful research-but bridging the two can lead to practical and ethical dilemmas. In order to provide practical guidance to researchers and epidemiologist, we set out to develop good epidemiological practice guidelines specifically for global health epidemiology, targeted at stakeholders involved in the commissioning, conduct, appraisal and publication of global health research. METHODS: We developed preliminary guidelines based on targeted online searches on existing best practices for epidemiological studies and sought to align these with key elements of global health research and research fairness. We validated these guidelines through a Delphi consultation study, to reach a consensus among a wide representation of stakeholders. RESULTS: A total of 45 experts provided input on the first round of e-Delphi consultation and 40 in the second. Respondents covered a range of organisations (including for example academia, ministries, NGOs, research funders, technical agencies) involved in epidemiological studies from countries around the world (Europe: 19; Africa: 10; North America: 7; Asia: 5; South-America: 3 Australia: 1). A selection of eight experts were invited for a face-to-face meeting. The final guidelines consist of a set of 6 standards and 42 accompanying criteria including study preparation, protocol development, data collection, data management, data analysis, dissemination and communication. CONCLUSION: While guidelines will not by themselves guard global health from questionable and unfair research practices, they are certainly part of a concerted effort to ensure not only mutual accountability between individual researchers, their institutions and their funders but most importantly their joint accountability towards the communities they study and society at large.