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Health research mentorship in low-income and middle-income countries: a global qualitative evidence synthesis of data from a crowdsourcing open call and scoping review.
Get PDFINTRODUCTION: Research mentorship is critical for advancing science, but there are few practical strategies for cultivating mentorship in health research resource-limited settings. WHO/TDR Global commissioned a group to develop a practical guide on research mentorship. This global qualitative evidence synthesis included data from a crowdsourcing open call and scoping review to identify and propose strategies to enhance research mentorship in low/middle-income country (LMIC) institutions.
METHODS: The crowdsourcing open call used methods recommended by WHO/TDR and solicited descriptions of strategies to enhance research mentorship in LMICs. The scoping review used the Cochrane Handbook and predefined the approach in a protocol. We extracted studies focused on enhancing health research mentorship in LMICs. Textual data describing research mentorship strategies from the open call and studies from the scoping review were coded into themes. The quality of evidence supporting themes was assessed using the Confidence in the Evidence from Reviews of Qualitative research approach.
RESULTS: The open call solicited 46 practical strategies and the scoping review identified 77 studies. We identified the following strategies to enhance research mentorship: recognising mentorship as an institutional responsibility that should be provided and expected from all team members (8 strategies, 15 studies; moderate confidence); leveraging existing research and training resources to enhance research mentorship (15 strategies, 49 studies; moderate confidence); digital tools to match mentors and mentees and sustain mentorship relations over time (14 strategies, 11 studies; low confidence); nurturing a culture of generosity so that people who receive mentorship then become mentors to others (7 strategies, 7 studies; low confidence); peer mentorship defined as informal and formal support from one researcher to another who is at a similar career stage (16 strategies, 12 studies; low confidence).
INTERPRETATION: Research mentorship is a collective institutional responsibility, and it can be strengthened in resource-limited institutions by leveraging already existing resources. The evidence from the crowdsourcing open call and scoping review informed a WHO/TDR practical guide. There is a need for more formal research mentorship programmes in LMIC institutions
Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway.
Get PDFOBJECTIVES: This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group.
DESIGN AND SETTING: Test-negative design (TND), multicentre case-control study with additional population controls in South-Eastern Norway.
PARTICIPANTS: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls.
PRIMARY OUTCOME MEASURES: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group.
RESULTS: In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8).
CONCLUSIONS: Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case-control study designs during the pandemic
Sleeplessness and incident diabetes above the Arctic circle: a secondary analysis of cohort data from the Tromsø Study.
Get PDFINTRODUCTION: Circadian misalignment and sleep quality are intertwined processes that are both associated with diabetes. The association between sleep quality and incident diabetes has not been previously investigated in populations living at polar latitudes who experience extreme seasonal daylight variation and may be at greater risk of circadian misalignment. Using data from adult residents of Tromsø, Norway, this study investigates the association of poor sleep quality, as indicated by self-reported sleeplessness, and incident diabetes above the Arctic circle.
RESEARCH DESIGN AND METHODS: Secondary analysis of cohort data from the Tromsø Study. The study cohort consists of adults who attended both the fourth (Tromsø4) and seventh (Tromsø7) surveys conducted in 1995 and 2016, respectively. Only individuals with complete data were included. Multivariable logistic regression was used to examine the association between sleeplessness measured in Tromsø4 and incident diabetes measured in participants followed up to Tromsø7, adjusted for other diabetes risk factors. RESULTS: Among 10 875 individuals (mean 41 years of age at baseline, 53.6% women), 21.2% (n=2302) reported experiencing sleeplessness at baseline. Diabetes incidence risk over follow-up (20 years) was 7.2% (n=784); incidence risk among individuals reporting sleeplessness was 8.8%, compared with 6.8% among unexposed individuals. After adjustment, sleeplessness-exposed individuals in the study cohort were found to have 23% greater odds (ORadj 1.23, 95% CI 1.03 to 1.47, p=0.022) of incident diabetes.
CONCLUSIONS: Sleep quality is associated with incident diabetes in a population living above the Arctic circle. The direction and strength of association is consistent with findings from other geographical regions
Constipation preceding depression: a population-based cohort study.
Get PDFBACKGROUND: Constipation is generally considered a common physical symptom of depression or a side effect of antidepressant treatments. However, according to the gut-brain axis hypothesis, the association between depression and constipation might be bi-directional. This study investigated the association between premorbid constipation and depression.
METHODS: We conducted a retrospective cohort study using data from UK Biobank. Individuals free of depression between 2006 and 2010 were included. Constipation status was determined using diagnostic codes from electronic health records or a baseline questionnaire. Data on covariates, including socio-demographic characteristics, lifestyle factors, health conditions, and regular medication use, were also collected through a baseline questionnaire. The primary outcome is incident depression, which was extracted from hospital inpatient admissions, primary care, self-report, and death data from baseline to 2022. The secondary outcome is depressive symptoms, which was assessed by Patient Health Questionnaire-9 (PHQ-9) from an online survey in 2016. Cox proportional hazard regression models were employed to assess the prospective association between constipation and incident depression. Logistic regression models were used to assess its association with depressive symptoms.
FINDINGS: Among the 449,459 participants included in the study, 18,596 (4.1%) experienced constipation at baseline, and 18,576 (4.1%) developed depression over a median follow-up period of 12.3 years. Premorbid constipation is associated with a 2.28-fold higher risk of depression. After adjusting the covariates, we found those with constipation still had a 48% higher risk of developing depression (adjusted hazard ratio [aHR] 1.48; 95% CI, 1.41-1.56) than those without constipation. Self-reported and diagnosed constipation were both associated with a higher risk of depression, with the aHR being 1.42 (95% CI: 1.34-1.51) and 1.66 (95% CI: 1.51-1.82), respectively. Participants with constipation were more likely to report depressive symptoms than people without (adjusted odds ratio 2.18; 95% CI, 1.97-2.43). These findings remained consistent in sensitivity analyses.
INTERPRETATION: Diagnosed and self-reported constipation are both prospectively associated with an elevated risk of depression. These explorative findings suggest that constipation may be an independent risk factor or a prodromal symptom of depression. Gastroenterologists and primary care physicians should pay more attention to the depressive symptoms of their constipation patients.
FUNDING: The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences
Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials.
Get PDFAIMS: Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR-Preserved and EMPEROR-Reduced trials.
METHODS AND RESULTS: Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy-terminal propeptide (PICP), a fragment of N-terminal type III collagen (PRO-C3), procollagen type I amino-terminal peptide (PINP), a fragment of C-terminal type VIa3 collagen (PRO-C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO-C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high-sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO-C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO-C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91-0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88-0.97, p = 0.003). Additionally, empagliflozin reduced PRO-C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95-1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89-0.98, p = 0.003), without impact on other collagen markers.
CONCLUSION: Our observations are consistent with experimental observations that empagliflozin down-regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated
Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis.
Get PDFBACKGROUND: Few studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016.
METHODS: We conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015-February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings.
FINDINGS: The average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62.81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisation in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden.
INTERPRETATION: We did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults.
FUNDING: Pfizer clinical research collaboration agreement (contract number: WI236621)
Do children with disabilities have the same opportunities to play as children without disabilities? Evidence from the multiple indicator cluster surveys in 38 low and middle-income countries.
Get PDFBACKGROUND: Play is essential for the cognitive, social, and emotional development of all children. Disparities potentially exist in access to play for children with disabilities, and the extent of this inequity is unknown.
METHODS: Data from 212,194 children aged 2-4 years in 38 Low and Middle-Income Countries were collected in the UNICEF supported Multiple Indicator Cluster Survey (2017-2020). Disability was assessed by the Washington Group-Child Functioning Module. Logistic regression models were applied to investigate the relationship between disability and play opportunities, controlling for age, sex, and wealth status. Meta-analysis was used to pool the estimates (overall, and disaggregated by sex), with heterogeneity assessed by Cochran's Q test.
FINDINGS: Children with disabilities have approximately 9% fewer play opportunities than those without disabilities (adjusted RR [aRR] = 0.88, 95% CI = 0.82-0.93), and this varied across countries. Mongolia and Democratic Republic of São Tomé and Príncipe had the lowest likelihood of play opportunities for children with disabilities ((aRR = 0.26, 95% CI = 0.09-0.75; aRR = 0.46, 95% CI = 0.23-0.93, respectively). Moreover, children with disabilities are 17% less likely to be provided with opportunities to play with their mothers (aRR = 0.83, 95% CI: 0.73-0.93), which is further reduced for girls with disabilities (aRR = 0.74, 95% CI: 0.60-0.90) compared to their peers without disabilities. The associations varied by impairment type, and children with communication and learning impairments are less likely to have opportunities for play with aRR of 0.69 (95% CI: 0.60-0.79) and 0.78 (95% CI: 0.71-0.86), compared to those without disabilities, respectively.
INTERPRETATION: Children with disabilities are being left behind in their access to play and this is likely to have negative impacts on their overall development and well-being. FUNDING: HK and TS are funded by HK's NIHR Global Research Professorship (NIHR301621). SR is funded by a Rhodes Scholarship. This study was funded by the Programme for Evidence to Inform Disability Action (PENDA) grant from the UK Foreign, Commonwealth and Development Office
The Burden of Chagas Disease in the Contemporary World: The RAISE Study.
Get PDFChagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda
Synergism of red blood cells and tranexamic acid in the inhibition of fibrinolysis.
Get PDFBACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. The World Maternal Antifibrinolytic trial showed that antifibrinolytic tranexamic acid (TXA) reduces PPH deaths. Maternal anemia increases the risk of PPH. The World Maternal Antifibrinolytic-2 trial is now assessing whether TXA can prevent PPH in women with anemia. Low red blood cell (RBC) counts promote fibrinolysis by altering fibrin structure and plasminogen activation.
OBJECTIVES: We explored interactions between RBCs and TXA in inhibiting fibrinolysis.
METHODS: We used global fibrinolytic assays (ball sedimentation and viscoelasticity) to monitor the lysis of fibrin containing plasminogen and tissue-type plasminogen activator. We applied a fluorogenic kinetic assay to measure plasmin generation in fibrin clots and scanning electron microscopy to study fibrin structure.
RESULTS: According to parallel-line bioassay analysis of the fibrin lysis-time data, the antifibrinolytic potency of 4-128 μM TXA was increased in the presence of 10% to 40% (v/v) RBCs. Global fibrinolysis assays showed that the joint effect of RBCs and TXA was about 15% larger than the sum of their individual effects in the inhibition of fibrinolysis. In plasminogen activation, TXA added the same increment of inhibition to the effect of RBCs at any cell count in the fibrin clot. Regarding fibrin structure, TXA thickened fibrin fibers, which impaired plasminogen activation, whereas RBCs promoted fine fibers that were more resistant to plasmin. CONCLUSIONS: The antifibrinolytic potency of TXA is enhanced in fibrin formed in the presence of RBCs through inhibition of plasminogen activation and fibrin lysis, which correlates with modifications of fibrin structures
Progress Towards Elimination of Trachoma in Kenya 2017-2020.
Get PDFPURPOSE: Trachoma is endemic in Kenya. Since baseline trachoma surveys in 2004, a concerted programme has been undertaken to reduce the prevalence of disease. Here, we report on trachoma prevalence surveys carried out between 2017 and 2020 after interventions were implemented in some areas for trachoma elimination purposes. METHODS: A total of 48 cross-sectional population-based trachoma prevalence surveys were conducted in 39 evaluation units (EUs; covering 45 subcounties) of Kenya between 2017 and 2020. Thirty EUs were surveyed once and nine EUs were surveyed twice over this period. Individuals ≥ 1 year old were assessed for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI) and trichiasis. Data were collected on household access to water, sanitation and hygiene (WASH). RESULTS: A total of 147,573 people were examined. At the end of 2020, in the 39 EUs surveyed, the prevalence of TF in 1-9-year-olds was ≥5% in 11 EUs and the prevalence of trichiasis unknown to the health system in individuals aged ≥15 years was ≥0.2% in 25 EUs. A small minority of households (median <50% for all indicators) had access to improved WASH facilities. CONCLUSION: Kenya has made excellent progress towards elimination of trachoma as a public health problem. However, there is more work to do. Between one and three rounds of antibiotic mass drug administration are required in 11 EUs. Sustained investment in surgical provision, continued TT case-finding, promotion of facial cleanliness and environmental improvement are required throughout the surveyed area