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"Butterflies in a jar": How girls and young women conceptualise wellbeing in conflict-affected Myanmar
Get PDFSince the 2021 coup in Myanmar, the country has been driven into further social, political and economic turmoil. The United Nations estimates that 18.6 million people need humanitarian support. Among those most affected are adolescent girls aged 10–19 years who, as adolescents and young women, face unique risks to their health and wellbeing and require tailored interventions to promote their health and wellbeing both now and in the future. Supporting adolescent girls and young women during conflict means addressing their increased risk of gender-based violence, forced marriage, disrupted education, and access to health services. There is limited evidence on the effects of Myanmar's current political situation on adolescent girls and young women, and even less on what can be done to support their health and wellbeing during this period of protracted instability. In this qualitative study, we used the capabilities approach to conceptualise wellbeing from the perspectives of adolescent girls and young women in Myanmar. Collaborating with four young female peer-researchers, we conducted 12 participatory focus group discussions with 73 girls from Yangon, Sagaing and Mandalay. Our findings identified key themes of wellbeing that were prioritised by our study population: education, agency, hope and happiness, which were being undermined by gender inequality and the ongoing conflict. This study highlights the benefits of the capabilities approach in identifying the complex wellbeing needs of adolescent girls and young women in crisis settings as a basis for programme design and implementation
"Ashamed of being seen in an HIV clinic": a qualitative analysis of barriers to engaging in HIV care from the perspectives of patients and healthcare workers in the Daraja clinical trial.
Get PDFBACKGROUND: There is high post-hospital discharge mortality among persons with HIV who are hospitalized, and post-hospital survival is strongly associated with early HIV clinic linkage, clinic attendance, and antiretroviral therapy adherence. The Daraja intervention, a context-tailored case management strategy implemented and tested through a randomized trial in Tanzania, was associated with improved HIV clinic linkage, retention, and ART initiation and adherence. METHODS: We conducted in-depth interviews (IDIs) in a sub-sample of 40 study participants (20 control and 20 intervention) 12 months after enrollment into the trial to gain an in-depth understanding of the barriers to HIV care engagement and the perceived mechanisms through which the Daraja intervention impacted these barriers. We also conducted IDIs with 20 health care providers. We used a thematic analysis approach to generate themes following the Gelberg-Andersen behavioral model for vulnerable population domains. RESULTS: Perceived stigma, coupled with the mistrust of healthcare providers, underemployment or lack of reliable income, unreliable transport, and a lack of social support, were identified as key barriers to HIV clinic attendance and ART adherence. Perceived stigma complicated not only linking to and attending an HIV clinic but also decision-making regarding the choice of the clinic's location. The Daraja intervention was reported to help normalise HIV diagnosis, plug the social support gap, increase patients' self-efficacy and their capacity of participants to navigate the HIV clinic during HIV clinic linkage. CONCLUSION: These qualitative research results identified several important barriers to engaging in HIV care and provide insights into the mechanisms through which the Daraja intervention operated to affect the perceived stigma, social support, self-efficacy, and increased capacity of participants to navigate the HIV clinic during HIV clinic linkage. DARAJA TRIAL REGISTRATION: ClinicalTrials.gov, NCT03858998. Registered on 01 March 2019
Blood Transfusions for Chronic Malaria Anemia in Prisoners of War on the Thai-Burma Railway 1943-1945.
Get PDFAllied prisoners of war (POWs) working on the Imperial Japanese Army's railroad from Thailand to Burma during 1943-1945 devised a blood transfusion service to rescue severely ill fellow prisoners who were otherwise unlikely to survive the war. Extant transfusion records (1,251 recipients, 1,189 donors) in ledger books held by the United Kingdom National Archives at Kew were accessed and analyzed. Survival to the end of the war in 1945 was determined from Commonwealth War Graves Commission records. The records examined indicate that freshly donated whole blood was manually defibrinated and transfused after crossmatches based on POW medic sera. Overall survival to the end of the war was 74% in recipients and 88% in donors. Postwar survival rates were significantly higher for transfusion recipients with malaria (89.3%) than for other diagnoses: 52.6% for malnutrition, 59.3% for dysentery, 67.2% for skin ulcers, and 75.4% for other causes (odds ratio: 3.97; 95% CI: 2.79-5.28; P <0.0001). By 1945, the vast majority of blood transfusions were given for severe anemia caused by chronic relapsing vivax malaria. Although the POW situation was admittedly extreme, our data provide evidence that blood transfusions to treat severe anemia were associated with higher survival among patients with Plasmodium vivax infection than among those with other morbidities
A Blueprint for Building Resilience and Food Security in MENA and SSA Drylands: Diversifying Agriculture With Neglected and Underutilized Species
Get PDFABSTRACT
Drylands, encompassing 41% of global land and supporting over 2 billion people, face significant challenges, including water scarcity, extreme temperatures, and soil degradation. Dryland spans vast areas of Middle East and North Africa (MENA) and Sub‐Sahara Africa (SSA) regions and poses a threat to food security and resilience. This study examines the potential of neglected and underutilized species (NUS) to improve dryland food and nutrition security, focusing on their agronomic performance, water productivity, economic viability, and nutritional benefits. Using long‐term data from FAOSTAT, USDA Food Data Central, and peer‐reviewed literature, we analyzed trends in the cultivation, yield, and nutritional contributions of 26 NUS across 22 countries in the MENA region comparing them with major staples—rice, wheat, and maize. Between 1961 and 2022, NUS crop areas in MENA fluctuated, decreasing by 7.0% since 2018 to 21.17 Mha. Despite this, NUS demonstrated superior water productivity—up to 30% higher than major cereals. For instance, sorghum and cowpea achieved 2.5 kg/m3 compared to maize (0.83 kg/m3) and wheat (0.91 kg/m3) and exhibited strong heat tolerance, withstanding temperatures of up to 42°C and 38°C, respectively. Despite a negative trade balance, NUS significantly contributed to dietary calories, surpassing wheat. A field experiment in Merchouch, Morocco, confirmed that NUS offered a higher economic value per unit than wheat, and outperformed conventional crops across key indicators. Integrating NUS into dryland farming systems can enhance food security, sustainability, and resilience to climate change. Advancing NUS requires breeding programs, tailored good agricultural practices, value addition and market linkage, supportive policies, and farmer education. Collaborative efforts among international organizations, governments, and civil society are crucial to mainstreaming NUS in agrifood systems and contributing to the diversity, sustainability, and resilience of dryland farming systems in MENA and SSA regions
Socio-economic inequalities in second primary cancer incidence: A competing risks analysis of women with breast cancer in England between 2000 and 2018.
Get PDFWe aimed to investigate socio-economic inequalities in second primary cancer (SPC) incidence among breast cancer survivors. Using Data from cancer registries in England, we included all women diagnosed with a first primary breast cancer (PBC) between 2000 and 2018 and aged between 18 and 99 years and followed them up from 6 months after the PBC diagnosis until a SPC event, death, or right censoring, whichever came first. We used flexible parametric survival models adjusting for age and year of PBC diagnosis, ethnicity, PBC tumour stage, comorbidity, and PBC treatments to model the cause-specific hazards of SPC incidence and death according to income deprivation, and then estimated standardised cumulative incidences of SPC by deprivation, taking death as the competing event. Multiple imputation was performed to account for missing data. Among 649,905 included women, 47,399 SPCs and 171,223 deaths occurred during 4,269,042 person-years of follow-up. Income deprivation was consistently associated with an increased rate of SPC incidence (cause-specific hazard ratio for the most vs. least deprived quintile: 1.29; 95% CI: 1.25, 1.33) and of death (1.36; 1.34, 1.38), translating into an absolute risk difference (the most vs. least deprived quintile) of 1.3% (95% CI: 1.0, 1.5) for SPC incidence and 4.9% (95% CI: 4.6, 5.1) for death at 10 years. Women with PBC from deprived areas in England faced a substantially higher risk of SPC than their counterparts. Future research is warranted to understand mechanisms for observed inequalities to inform strategies to monitor, prevent, and identify SPC in women with PBC
Target-agnostic identification of human antibodies to Plasmodium falciparum sexual forms reveals cross-stage recognition of glutamate-rich repeats
Get PDFCirculating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of Pf in the form of gametes and gametocyte extracts. We isolated mAbs reactive against a range of Pf proteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition of Pf proteins, previously described only for Pf circumsporozoite protein (PfCSP), extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of the Plasmodium parasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response against Pf
Estimating hypothetical estimands with causal inference and missing data estimators in a diabetes trial case study
Get PDFThe ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical trial in type 2 diabetes, targeting the effects of randomised treatment, handling rescue treatment and discontinuation of randomised treatment using the so-called hypothetical strategy. We show how this can be estimated using mixed models for repeated measures, multiple imputation, inverse probability of treatment weighting, G-formula and G-estimation. We describe their assumptions and practical details of their implementation using packages in R. We report the results of these analyses, broadly finding similar estimates and standard errors across the estimators. We discuss various considerations relevant when choosing an estimation approach, including computational time, how to handle missing data, whether to include post intercurrent event data in the analysis, whether and how to adjust for additional time-varying confounders, and whether and how to model different types of intercurrent event data separately
Potential interactions between antimicrobials and direct oral anticoagulants: population-based cohort and case-crossover study.
Get PDFBACKGROUND: Although drug interactions between clarithromycin/erythromycin/fluconazole and direct oral anticoagulants (DOACs) are mechanistically plausible, it is uncertain whether they are clinically relevant. OBJECTIVE: To investigate the association between co-prescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality. METHODS: We identified DOAC users in the Clinical Practice Research Datalink Aurum from 1/1/2011-29/3/2021. We used a cohort design to estimate hazard ratios for bleeding outcomes (intracranial bleeding, gastrointestinal bleeding, other bleeding), comparing DOACs+clarithromycin/erythromycin/fluconazole users with DOACs users not receiving these antimicrobials. Cardiovascular outcomes were ischaemic stroke, myocardial infarction, venous thromboembolism, cardiovascular mortality and all-cause mortality. A 6-parameter case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window versus referent window within an individual was also conducted. RESULTS: Of 483,815 DOAC users, we identified 21,701 co-prescribed clarithromycin, 4,532 co-prescribed erythromycin and 4,840 co-prescribed fluconazole. We observed an increased risk of gastrointestinal bleeding over 7-days following co-prescription of DOAC+erythromycin versus DOAC alone (HR:3.66; 99%CI:1.27-10.51), with wide CIs in case-crossover analysis. No evidence of increased risk of bleeding outcomes was seen for DOAC+clarithromycin/fluconazole in cohort and case-crossover analyses. For cardiovascular outcomes, compared with DOAC alone, an increased risk of cardiovascular mortality with DOAC+clarithromycin(HR:3.36; 99%CI:1.73-6.52) and increased risk of all-cause mortality with DOAC+clarithromycin/erythromycin/fluconazole were observed in cohort analysis. However, similar risks were found when initiating erythromycin/fluconazole with and without DOAC. CONCLUSION: We found no strong evidence of increased risks of bleeding and cardiovascular outcomes in DOACs+clarithromycin/fluconazole/erythromycin users except a possible short-term increased risk of gastrointestinal bleeding in DOACs+erythromycin users
Impact of commercial gut health interventions on caecal metagenome and broiler performance.
Get PDFBACKGROUND: Maintaining gut health is a persistent and unresolved challenge in the poultry industry. Given the critical role of gut health in chicken performance and welfare, there is a pressing need to identify effective gut health intervention (GHI) strategies to ensure optimal outcomes in poultry farming. In this study, across three broiler production cycles, we compared the metagenomes and performance of broilers provided with ionophores (as the control group) against birds subjected to five different GHI combinations involving vaccination, probiotics, prebiotics, essential oils, and reduction of ionophore use. RESULTS: Using a binning strategy, 84 (≥ 75% completeness, ≤ 5% contamination) metagenome-assembled genomes (MAGs) from 118 caecal samples were recovered and annotated for their metabolic potential. The majority of these (n = 52, 61%) had a differential response across all cohorts and are associated with the performance parameter - European poultry efficiency factor (EPEF). The control group exhibited the highest EPEF, followed closely by the cohort where probiotics are used in conjunction with vaccination. The use of probiotics B, a commercial Bacillus strain-based formulation, was determined to contribute to the superior performance of birds. GHI supplementation generally affected the abundance of microbial enzymes relating to carbohydrate and protein digestion and metabolic pathways relating to energy, nucleotide synthesis, short-chain fatty acid synthesis, and drug-transport systems. These shifts are hypothesised to differentiate performance among groups and cycles, highlighting the beneficial role of several bacteria, including Rikenella microfusus and UBA7160 species. CONCLUSIONS: All GHIs are shown to be effective methods for gut microbial modulation, with varying influences on MAG diversity, composition, and microbial functions. These metagenomic insights greatly enhance our understanding of microbiota-related metabolic pathways, enabling us to devise strategies against enteric pathogens related to poultry products and presenting new opportunities to improve overall poultry performance and health. Video Abstract
Harmonizing population health data into OMOP common data model: a demonstration using COVID-19 sero-surveillance data from Nairobi Urban Health and Demographic Surveillance System
Get PDFBackground:
Observational health data are collected in different formats and structures, making it challenging to analyze with common tools. The Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) is a standardized data model that can harmonize observational health data.
Objective:
This paper demonstrates the use of the OMOP CDM to harmonize COVID-19 sero-surveillance data from the Nairobi Urban Health and Demographic Surveillance System (HDSS).
Methods:
In this study, we extracted data from the Nairobi Urban HDSS COVID-19 sero-surveillance database and mapped it to the OMOP CDM. We used open-source Observational Health Data Sciences and Informatics (OHDSI) tools like WhiteRabbit, RabbitInAHat, and USAGI. The steps included data profiling (scanning), mapping the vocabularies using the offline USAGI and online ATHENA, and designing the extract, transform, and load (ETL) process using RabbitInAHat. The ETL process was implemented using Pentaho Data Integration community edition software and structured query language (SQL). The target OMOP CDM can now be used to analyze the prevalence of COVID-19 antibodies in the Nairobi Urban HDSS population.
Results:
We successfully mapped the Nairobi Urban HDSS COVID-19 sero-surveillance data to the OMOP CDM. The standardized dataset included information on demographics, COVID-19 symptoms, vaccination, and COVID-19 antibody test results.
Conclusions:
The OMOP CDM is a valuable tool for harmonizing observational health data. Using the OMOP CDM facilitates the sharing and analysis of observational health data, leading to a better understanding of disease conditions and trends and improving evidence-based population health strategies