69832 research outputs found
Sort by
Effect of intrapartum azithromycin on early childhood gut mycobiota development: post hoc analysis of a double-blind randomized trial.
Get PDFIntrapartum azithromycin prophylaxis reduced maternal infections but showed no effect on neonatal sepsis and mortality. Although antibiotic exposure may indirectly alter the mycobiota (community of fungi that live in a given environment), there is no data available on how intrapartum azithromycin impacts gut mycobiota development. We hereby assess the impact of intrapartum azithromycin on gut mycobiota development from birth to the age of three years, by ITS2 gene profiling of rectal samples from 102 healthy Gambian infants selected from a double-blind randomized placebo-controlled clinical trial (PregnAnZI-2 - ClinicalTrials.org NCT03199547). In the trial, women received 2 g oral azithromycin or placebo (1:1) during labour with the intension of assessing effect on neonatal sepsis or mortality. Secondary objectives included effects on bacterial carriage and resistance, puerperal infections, and infant growth. Our analysis show that season and parity were key factors that influenced gut mycobiota development. Intrapartum azithromycin increased the abundance of Candida orthopsilosis but only in the wet season and did not show different effects by sex of the child. These data suggest that season and parity can be key factors influencing gut mycobiota development and may inform strategies for a wider implementation of intrapartum azithromycin intervention
Socioeconomic pattern of breastfeeding in sub-Saharan Africa: an individual participant data meta-analysis of six longitudinal cohorts.
Get PDFBACKGROUND: Breastfeeding rates in sub-Saharan Africa (SSA) are declining, and at the current rate, only four African countries will meet the WHO's 2030 exclusive breastfeeding target. We examined the association between maternal socioeconomic status (SES) and breastfeeding practices in SSA. METHODS: Six cohorts in Ethiopia, Malawi, Uganda and Zambia, with 11 863 participants, were analysed. Data for the cohorts were collected between 2000 and 2021, covering births from 2000 to 2019. SES exposures were maternal education and household income. Breastfeeding outcomes included ever breastfed, early initiation of breastfeeding (Ethiopia only), exclusive breastfeeding for ≥4 months or ≥6 months, and continued breastfeeding for ≥1 year. Risk ratios from multivariable Poisson regression models for individual cohorts were pooled in a random-effects meta-analysis to assess the effects of SES on breastfeeding, adjusting for confounders. RESULTS: Meta-analysis found no evidence of a difference in ever breastfeeding between mothers with secondary or tertiary education and those with primary/no education. Mothers with secondary education (adjusted risk ratio (aRR)=1.11, 95% CI=1.01 to 1.21) and those from middle-wealth households (aRR=1.12, 95% CI=1.01 to 1.24) were more likely to initiate breastfeeding early than those with primary/no education or low household wealth, but there was no evidence of association in the tertiary education and higher-wealth groups. The association between maternal education and exclusive breastfeeding for ≥4 months and ≥6 months varied across cohorts, with no evidence of association in most cohorts. Overall, household wealth was not associated with exclusive breastfeeding for ≥4 months or ≥6 months. The meta-analysis showed no evidence of association between household wealth and breastfeeding for ≥1 year, but mothers with tertiary education were less likely (aRR=0.93, 95% CI=0.88 to 0.99) to breastfeed for ≥1 year than those with primary or no education. CONCLUSION: We observed no clear socioeconomic pattern in breastfeeding, contrasting with patterns observed in high-income countries
Causes and MEchanisms foR non-atopic Asthma in Children (CAMERA) study: rationale and protocol.
Get PDFBACKGROUND: The Causes And MEchanisms foR non-atopic Asthma in children (CAMERA) study was designed to investigate risk factors and mechanisms of non-atopic asthma in children and young adults in Brazil, Ecuador, Uganda, and New Zealand. Initial epidemiological analyses using existing datasets identified and compared risk factors for both atopic and non-atopic asthma. The focus of this paper is the protocol for sample collection and analysis of clinical data on possible non-atopic mechanisms. METHODS: In each of the four centres, the CAMERA study will enroll 160 participants aged 10-28 years, equally distributed among atopic asthmatics (AA), non-atopic asthmatics (NAA), atopic non-asthmatics and non-atopic non-asthmatics. Participants will be new recruits or returning World ASthma Phenotypes (WASP) study participants. Phase I consists of skin prick tests to define atopy, a general CAMERA questionnaire that covers respiratory and general health to identify asthma cases, followed by an asthma control questionnaire for asthmatics only. Phase II consists of a stress questionnaire and the following clinical assessments: lung function, nasal cytology, blood sampling, in vitro whole blood stimulation to assess IFN-γ production, hair cortisol concentration, dry air and capsaicin challenges, plus in a subset, cold air challenges. Analyses will compare inflammatory, physiological and clinical parameters across the four groups overall and by country. DISCUSSION: Here, we present the protocol for the CAMERA study, to provide relevant methodological details for CAMERA publications and to allow other centres globally to conduct similar analyses. The findings of this mechanistic multi-centre study will inform new and phenotype-specific prevention and treatment approaches. CLINICAL TRIAL NUMBER: Not applicable
Methodological opportunities in genomic data analysis to advance health equity.
Get PDFThe causes and consequences of inequities in genomic research and medicine are complex and widespread. However, it is widely acknowledged that underrepresentation of diverse populations in human genetics research risks exacerbating existing health disparities. Efforts to improve diversity are ongoing, but an often-overlooked source of inequity is the choice of analytical methods used to process, analyse and interpret genomic data. This choice can influence all areas of genomic research, from genome-wide association studies and polygenic score development to variant prioritization and functional genomics. New statistical and machine learning techniques to understand, quantify and correct for the impact of biases in genomic data are emerging within the wider genomic research and genomic medicine ecosystems. At this crucial time point, it is important to clarify where improvements in methods and practices can, or cannot, have a role in improving equity in genomics. Here, we review existing approaches to promote equity and fairness in statistical analysis for genomics, and propose future methodological developments that are likely to yield the most impact for equity
Pay-it-forward and social network distribution to increase doxycycline post-exposure prophylaxis uptake among men who have sex with men and transgender women in China: study protocol for a three-arm randomised controlled trial.
Get PDFINTRODUCTION: Doxycycline postexposure prophylaxis (doxy-PEP) can prevent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW). STI rates are high among MSM and TGW in China, and implementation strategies are needed to optimise doxy-PEP services. Pay-it-forward and social network distribution approaches may increase uptake of STI services and could increase the uptake of doxy-PEP. We present the protocol for a randomised controlled trial evaluating the effectiveness of pay-it-forward strategies with and without adjunctive social network distribution among MSM and TGW in China.
METHODS AND ANALYSIS: A total of 399 MSM and TGW will be recruited at seven sites in China and randomly allocated in a 1:1:1 ratio to (1) self-pay, (2) pay-it-forward alone or (3) pay-it-forward with adjunctive social network distribution of doxy-PEP. Participants assigned to the self-pay arm can purchase a doxy-PEP packet out-of-pocket. Participants in the pay-it-forward arm will be offered a free doxy-PEP packet and the opportunity to donate to support doxy-PEP for future participants. Participants in the pay-it-forward arm with social network distribution will receive the pay-it-forward intervention as well as additional free doxy-PEP packets to distribute to peers. Those randomised to the self-pay and the pay-it-forward with social network distribution arms (ie, index participants) will receive and distribute referral cards to recruit additional peers (ie, alter participants). Alter participants recruited through the control arm will be referred to the clinic to purchase doxy-PEP. Alter participants recruited through the pay-it-forward with adjunctive social network distribution arm will receive doxy-PEP directly from referring index participants. Both index and alter participants in each arm will be asked to complete a follow-up survey 3 and 6 months after enrolment. The primary outcome will be the proportion of participants who report using doxy-PEP within 72-hours of condomless anal or oral sex on one or more occasions during follow-up.
ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics review committee of the Dermatology Hospital of Southern Medical University (Approval number: 2023109). The findings will be disseminated in peer-reviewed publications.
TRIAL REGISTRATION NUMBER: The study has been registered with the Chinese Clinical Trial Registry (trial ID ChiCTR2300074903). Date of registration: 18 August 2023
Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review.
Get PDFABSTRACT: Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data-driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti-inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms. HIGHLIGHTS: ·We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia.·Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment.·Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue.·Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia
War-time mortality in Sudan: a multiple systems estimation analysis.
Get PDFBACKGROUND: The mortality impact of war in Sudan, which began in April 2023, remains largely unmeasured due to sparse and methodologically weak data that reflect sparse pre-war vital registration systems and actively restricted access to affected communities. Our study aimed to quantify undocumented war-time mortality levels and patterns in Sudan. METHODS: We conducted a retrospective observational study collecting lists of people deceased since April 15, 2023, from three sources: a public social media survey, a survey disseminated through private networks, and public social media obituaries. After probabilistically matching decedent records within and across lists, we described age and cause-of-death patterns by region and month. For Khartoum State, where data were sufficiently abundant, we used multiple systems estimation to estimate all-cause and intentional-injury mortality. FINDINGS: In the war's first 14 months, most reported deaths were from preventable causes, while intentional-injury deaths were disproportionately high in Khartoum State and Gezira State, and highest in the Kordofan and Darfur regions. We estimate that 61 202 all-cause deaths (95% CI 22 286-209 151) occurred in Khartoum State between April 2023, and June 2024, corresponding to a conservatively estimated crude death rate of 9·7 per 1000 persons per year. 26 024 deaths (95% CI 12 571-58 704) in Khartoum were due to intentional injuries. INTERPRETATION: Between April 2023, and June 2024, Sudan's war likely caused a substantial, largely undocumented rise in mortality in Khartoum State, with intentional-injury deaths in the capital alone exceeding the ACLED reported fatalities toll for the same period (ie, 20 178). Across the country mortality was driven by preventable disease and hunger, with intentional-injury deaths predominating in the Darfur and Kordofan regions. Urgent diplomatic and humanitarian action is critical to prevent further avoidable deaths, deter human rights violations, and to support post-conflict recovery and reconciliation. FUNDING: Centers for Disease Control and Prevention of the US Department of Health and Human Services (as part of financial assistance award U01GH002319) and the UK Foreign, Commonwealth & Development Office
Relative and attributable risks of neurological and perinatal adverse outcomes among children with and without prenatal Zika virus exposure in Northeast Brazil: A prospective cohort study (2015-2018).
Get PDFBACKGROUND: Although there has been substantial progress in the characterization of Congenital Zika Syndrome, the lack of a control group in the majority of published studies on Zika virus (ZIKV) infections during pregnancy limits our understanding of, first, the magnitude by which prenatal ZIKV exposure may increase risks of adverse outcomes for offspring and, second, the fraction of abnormalities that are attributable to this exposure. METHODS: To overcome this limitation, this study harmonized and integrated data collected prospectively in Recife, Pernambuco, Brazil, from offspring of ZIKV-exposed women in the Microcephaly Epidemic Research Group (MERG) Pregnant Women Cohort and from offspring of ZIKV-unexposed women in the Zika in Infants and Pregnancy (ZIP) Study. We compared the data to estimate the relative risk (RR) and attributable risk percent (AR%) of: (i) adverse birth outcomes including low birth weight (LBW), prematurity and small for gestational age (SGA) and (ii) developmental abnormalities including microcephaly and neurological, ophthalmological, audiological, and neuroimaging alterations. FINDINGS: We observed similar odds of adverse birth outcomes and ophthalmological deficits in ZIKV-exposed and unexposed children. However, as compared to ZIKV-unexposed children, ZIKV-exposed children presented with markedly increased risks of microcephaly (RR, 95%-CI: 3.61, 1.70 to 7.63 AR 72%), neurological abnormalities (RR, 95%-CI: 5.64, 3.04 to 10.47.79AR 82%), audiological screening failures (RR, 95%-CI: 9.20, 2.59 to 32.69 AR 89%), and neuroimaging abnormalities (RR, 95%-CI: 22.06, 2.90 to 167.5; AR 95%). The risk of having concurrent abnormalities was lower than the risk of having just one abnormality. Our results provide new insights into the relative and attributable risks related to prenatal ZIKV exposure and demonstrate that, overall, the risks of congenital abnormalities are elevated among children exposed to ZIKV during pregnancy compared to their ZIKV-unexposed peers
Towards a universal implementation of labor companionship: a synthesis of the policy and facility environment of eight low-and-middle income countries.
Get PDFBACKGROUND: Labor companionship, the presence of a woman's person of choice during childbirth, has benefits to both woman and baby and is recommended by the World Health Organization since 2012. However, implementation remains sub-optimal, especially in low-and-middle-income countries (LMICs). This study aimed to understand the maturity of labor companionship implementation in eight low-and-middle income countries with focus on the policy and facility environment. METHODS: This was a multi-country study nested in two hospital-based implementation research studies: Action Leveraging Evidence to Reduce perinatal mortality and morbidity in Sub-Saharan Africa (ALERT) study and the QUALIty DECision-making by women and providers for appropriate use of caesarean section (QUALI-DEC) study. We included 48 hospitals from eight countries: Argentina, Burkina Faso, Thailand and Viet Nam (QUALI-DEC) and four from each of Benin, Malawi, Tanzania and Uganda (ALERT). We used data from (i) a document review, including national policy documents and (ii) health facility readiness assessment, including physical layouts of maternity wards, all collected between December 2019 and April 2021. Our analysis included two steps, (1) a structured data abstraction with coding to pre-defined categories to analyse the national polices and available resources on a facility level which informed the (2) categorization of implementation maturity in three implementation phases modelled by the framework by Bergh et al. and the logic model developed by Bohren et al. RESULTS: Three of the eight countries lacked any national-level companionship policies, four had some mentioning and only one had detailed guidance on roles of labor companions and implementation guidelines. The physical outlines of maternity wards varied greatly, and lack of space was one of the main implementation barriers to all countries except Argentina. We classified Benin, Thailand and Viet Nam in the pre-implementation phase because of missing guidelines and limited implementation; Burkina Faso, Malawi, Uganda and Tanzania in the early implementation phase; and Argentina in the institutionalization phase where policies and facility resources were conducive. CONCLUSION: Successful implementation was supported by concrete and contextualized implementation guidance. To move to high implementation levels, supporting policies, guidelines and structural changes in the maternity wards are needed
Bivariate Copula Model on Fitting Correlated Time‐to‐Event Outcomes: Age at First Sex and Age at First Marriage Among Youth in Tanzania
Get PDFTraditionally, age at first sex (AFS) and age at first marriage (AFM) have been analysed independently. While useful for summarising risk factors for each outcome individually, these approaches offer limited insight into the interdependence between these events. This study used an Archimedean copula model for bivariate right‐censored data to jointly model AFS and AFM reported by 9726 young people aged 15–24 years in Kisesa, Tanzania. The dependence structure was identified, the degree of association between these events and their associated factors assessed, and the trends of predicted medians examined. Various Archimedean copulas (Ali–Mikhail–Haq, Clayton, Frank, Gumbel, Copula2, and Joe) were evaluated. Copula function selection was based on the Akaike information criterion (AIC), Bayesian information criterion (BIC), and log‐likelihood values, with the Frank copula and a log‐logistic marginal distribution performing best. The Frank copula’s dependency parameter (
θ
) was highly significant, with an estimated
θ
of 39.49, translating to a Kendall’s
τ
of 0.903 in the unadjusted model, which included only sex as a covariate, indicating a strong positive correlation between AFS and AFM. Similar results were observed in the adjusted model (Kendall’s
τ
= 0.89), which incorporated additional variables such as education and residence area. Trends show a better estimation of AFS and AFM for both females and males over the period 1994–2016 when analysed jointly rather than separately. The strong positive correlation suggests these events are highly correlated; hence, using joint models captures interdependence and provides more accurate estimates. This approach can inform targeted interventions to improve youth health outcomes