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Time trends and characteristics associated with abortion method used by young Australian women.
Get PDFOBJECTIVE: To explore time trends in abortion based on method used and characteristics associated with method type by uniquely linking social and behavioral data reported by a population-based cohort of young Australian women. METHODS: We analysed self-reported data from 16 993 women in the Australian Longitudinal Study on Women's Health 1989-95 cohort, aged 18-24 years at recruitment in 2013, linked to abortion data from three population-based administrative data sources. RESULTS: The incidence of medication abortion increased over time whereas surgical abortion decreased, with similar trends across the largest states. The adjusted odds ratio (AOR) of having a medication compared with a surgical abortion increased over time [by each 1-year increase in time, 1.33 (95% confidence interval 1.20, 1.48)]. Women who lived in outer regional/remote/very remote areas [AOR 3.51 (2.15, 5.74)] and inner regional areas [1.80 (1.21, 2.69)] had increased odds of a medication abortion compared with women who were living in major cities. Medication abortions were more common than surgical abortions in outer regional/remote/very remote areas from 2017 whereas, in major cities, surgical abortion remained the most common abortion method throughout the study period. CONCLUSION: Linkage of government-recorded health events with self-reports demonstrated a shift towards increasing use of medication abortion relative to surgical abortion, with greater increases in nonmetropolitan areas. The strong geographical disparities in abortion method suggest that, for those who are living in nonmetropolitan areas, there may be less opportunity to choose surgical abortion due to limited availability of services, with significant implications for women who present later in pregnancy
Rift Valley fever seroprevalence and risk factors among human populations in Uganda's cattle corridor: a cross-sectional study.
Get PDFINTRODUCTION: Rift Valley fever (RVF) is an epidemic-prone zoonotic disease whose distribution of exposure is poorly described in endemic communities. We investigated the seroprevalence and risk factors for RVF among humans in Uganda's cattle corridor. METHODS: This cross-sectional study used data and stored plasma specimens collected by the Uganda population-based HIV impact assessment (UPHIA) survey 2016/2017. Participants were sampled from 35 districts of the cattle corridor. Ethical and regulatory approvals were obtained to use the UPHIA data and to test the specimens for the presence of RVF anti-Gn glycoprotein immunoglobulin G (anti-Gn IgG) antibodies using an enzyme linked immunosorbent Assay (ELISA). RVF seroprevalence was calculated in Stata with household as the random intercept, and associations between potential determinants and RVF seropositivity were assessed using mixed effects logistic regression analysis. RESULTS: Overall, 267 households comprising 1319 individuals were included in the analysis. Over half (56.3%) of the participants were female, median age 22 (IQR 11-34) years. Most (84.2%) were rural and owned cattle (41.2%), sheep/goats (51.7%) and poultry (65%). The overall RVF seroprevalence was 10.24%, 95% CI 8.63% to 12.10%. RVF seropositivity was associated with advanced age (25-44 years adjusted OR 2.79 (95% CI 1.81 to 4.32); and 45-64 years (3.0 (95% CI 1.76 to 5.14)); ethnicity (Iteso 2.54 (95% CI 1.15 to 5.62), Langi 2.61 (95% CI 1.20 to 5.66) and Karamojong 3.70 (95% CI 1.61 to 8.47)); owning cattle (1.59 (95% CI 1.03 to 2.45)) and owning poultry (1.73 (95% CI 1.05 to 2.87)). CONCLUSIONS: RVF seropositivity is common among humans in Uganda's cattle corridor and the risk of exposure is mostly determined by increasing age, ethnicity, owning cattle and poultry. Future RVF seroprevalence and risk evaluation studies should include poultry as potential determinants of infection
Conceptualizing the implementation of post-discharge malaria chemoprevention in Malawi using a co-design approach.
Get PDFBACKGROUND: Severe malaria poses a significant challenge to under-five children in Malawi, leading to high rates of hospitalization and mortality. The World Health Organization has recently recommended post-discharge malaria chemoprevention (PDMC) as a preventive strategy for under-five children with severe anaemia in malaria-endemic regions. In response to this recommendation, Malawi's Ministry of Health (MoH) plans to implement PDMC nationwide. To facilitate effective implementation, the MoH has partnered with the Training and Research Unit of Excellence (TRUE) to conduct PDMC delivery trials to gather evidence for practical implementation in Malawi and similar settings. A key component of this initiative involved the MoH leading the co-design workshops with key stakeholders to foster collaboration, spur innovation, and develop user-centred strategies. This collaborative effort aimed to investigate optimal PDMC implementation strategies to guide the scale-up in Malawi and contribute to policy-making processes that enhance transparency, accountability, and ownership.
METHODS: This participatory action research occurred in the Salima district, Malawi, from 11 to 12 May 2023. Two co-design workshops were utilized, involving policymakers (n = 15), healthcare providers (n = 8), and prospective users (n = 2). The approach consisted of two stages. First, separate information-gathering sessions were held with policymakers, healthcare providers, and prospective users. Second, a structured discussion was facilitated, allowing collaboration between policymakers, healthcare providers, and prospective users to develop strategies for delivering and integrating the intervention. Discussions were audio recorded, transcribed verbatim, and manually analyzed using a thematic approach.
RESULTS: The inductive analysis yielded four overarching themes from the data. These key themes are PDMC adaptability, trialability, implementability, and sustainability. Stakeholders recommended adopting PDMC in Malawi, with health facilities as the optimal delivery option, ensuring that discharged children receive dihydroartemisinin-piperaquine doses for three months. PDMC aligns with existing systems, offering integration opportunities for managing childhood illnesses. However, gaps in policy development, approval, and health system strengthening-including supply chain, monitoring, evaluation, and follow-up-must be addressed to ensure PDMC's sustainability.
CONCLUSIONS: The co-design results indicate stakeholders' willingness to adopt and implement PDMC in Malawi. However, there is an awareness of the challenges that must be addressed to facilitate PDMC's successful implementation and sustainability
Development and validation of a dynamic nomogram for predicting cognitive impairment risk in older adults with dentures: analysis from CHARLS and CLHLS data.
Get PDFBACKGROUND AND AIMS: Cognitive impairment is a common issue among older adults, with denture use identified as a potential, easily recognizable clinical risk factor. However, the link between denture wear and cognitive decline in older Chinese adults remains understudied. This study aimed to develop and validate a dynamic nomogram to predict the risk of cognitive impairment in community-dwelling older adults who wear dentures.
METHODS: We selected 2066 elderly people with dentures from CHARLS2018 data as the development and internal validation group and 3840 people from CLHLS2018 as the external validation group. Develop and treat the concentrated unbalanced data with the synthetic minority oversampling technique, select the best predictors with the LASSO regression ten-fold cross-validation method, analyze the influencing factors of cognitive impairment in the elderly with dentures using Logistic regression, and construct a nomogram. Subject operating characteristic curves, sensitivity, specificity, accuracy, precision, F1 score, calibration curve, and decision curve were used to evaluate the validity of the model in terms of identification, calibration, and clinical validity.
RESULTS: We identified five factors (age, residence, education, instrumental activities of daily living, and depression) to construct the nomogram. The area under the curve of the prediction model was 0.854 (95%CI 0.839-0.870) in the development set, 0.841 (95%CI 0.805-0.877) in the internal validation set, and 0.856 (95%CI 0.838-0.873) in the external validation set. Calibration curves indicated significant agreement between predicted and actual values, and decision curve analysis demonstrated valuable clinical application.
CONCLUSIONS: Five risk factors, including age, place of residence, education, instrumental activities of daily living, and depression level, were selected as the final nomogram to predict the risk of cognitive impairment in elderly denture wearers. The nomogram has acceptable discrimination and can be used by healthcare professionals and community health workers to plan preventive interventions for cognitive impairment among older denture-wearing populations
Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics.
Get PDFThe current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis
The association of maternal mental health with vaccination coverage and timeliness in early childhood - A historical cohort study in England using electronic health records.
Get PDFBACKGROUND: Maternal mental illness (MMI) affects almost a quarter of mothers and may impact a child's development and physical health. It remains unclear whether MMI is associated with altered utilization of vaccination services. Understanding this association could help to identify families in need of additional support. METHODS: Using primary care data from England, we conducted a historical cohort study of 397,519 children born in England between 2006 and 2014 with linked maternal records. Associations between different types of MMI (common mental disorders, severe mental illness and alcohol and substance use disorder) with childhood immunisation were explored using logistic regression for differences in coverage and accelerated failure time models for differences in timeliness before the child's fifth birthday. RESULTS: While there were no differences in vaccination coverage at the age of one, children of mothers with common mental disorders had lower odds of being vaccinated at the ages of two (OR 0.95, 95 %CI: 0.93-0.98) and five (OR 0.86, 95 % CI 0.84-0.89) in comparison to children of mothers with no record of MMI. Vaccination coverage was even lower for children of mothers with comorbid substance disorder and common mental disorder (OR 0.70, 95 % CI: 0.62-0.78 at the age of five). There were no significant differences in timeliness of vaccine receipt by MMI. CONCLUSIONS: Inequalities in vaccination coverage associated with MMI grow with increasing age of the child. Extending support services for women with MMI beyond the child's first year of life could offer potential to improve vaccination uptake and reduce childhood infections
Sex-Specific Differences in the Progression of Huntington's Disease Symptoms - A National Study in China.
Get PDFINTRODUCTION: Huntington's disease (HD) is a rare, inherited neurodegenerative disorder. Despite extensive research on symptom progression and sex differences in Western populations, little is known about these aspects within the Chinese context. The objective of this study was to investigate the temporal trends of symptoms in individuals with HD in China.
METHODS: A nationwide cross-sectional study was conducted in Chinese individuals diagnosed with HD. Symptom progression over time, encompassing physical, psychiatric, and cognitive symptoms, was self-reported. We calculated the proportions of individuals who currently had each symptom by disease duration, and tested corresponding temporal trends by linear regression analyses.
RESULTS: A total of 269 individuals diagnosed with HD were included. Specific symptoms were found to progress more significantly in males compared to females over time, including psychotic symptoms (p = 0.007), urinary incontinence (p = 0.013), reduced concentration (p = 0.005), font alteration (p = 0.029), atypical facial expression (p = 0.037), and suicidal ideation (p = 0.047). In terms of cognitive and psychiatric symptoms, no significant temporal trends were identified in females, while males demonstrated significant increasing trends, with reduced concentration (p = 0.005) and psychotic symptoms (p = 0.007) standing out.
CONCLUSIONS: This study emphasizes the existence of sex-specific symptom progression in HD within the Chinese population, underscoring the importance of considering sex in clinical practice. Further research should investigate the mechanisms behind these differences and explore tailored treatment options
The microevolutionary trajectory of endemic multidrug-resistant tuberculosis strains in Portugal toward increased drug resistance levels and its clinical significance.
Get PDFPortugal has one of the highest incidence rates of tuberculosis (TB) in Western Europe and, historically, multidrug-resistant (MDR) cases have been strongly associated with Mycobacterium tuberculosis strains pertaining to the endemic Q1 and Lisboa3 clades. Notwithstanding, the contribution of drug resistance-associated allelic configurations in these clades to differing levels of drug resistance and their relationship with drug efficacy has yet to be uncovered. A representative sample of the drug-resistant M. tuberculosis population in Portugal, comprised of 40 clinical strains were subjected to whole genome sequencing for characterization of allelic combinations of drug resistance-associated mutations and their minimum inhibitory concentrations for 12 anti-TB drugs was determined. Pharmacokinetic (PK) models were generated to ascertain the maximum concentration to which each drug remains efficacious. Drug resistance levels were determined and compared between different allelic configurations. Double inhA and embA/B mutation genotypes contributed with increased isoniazid and ethambutol resistance levels compared with single mutation configurations, respectively. Significant differences in drug resistance levels were observed between phylogenetic groups for rifamycin, streptomycin and ethionamide, largely explained by the presence/absence of unique high-level resistance-associated genotypes. The PK models for isoniazid and moxifloxacin suggest an increase in dosage to be ineffective against strains harboring high-level resistance-conferring double inhA mutations and gyrA/B mutations. Cycloserine and para-aminosalicylic acid are the only drugs predicted to remain efficacious against the majority of tested strains, while the effectiveness of newer drugs like bedaquiline, pretomanid and delamanid have yet to be uncovered. Proper diagnosis of drug resistance-associated mutations provides invaluable insights into the treatment of TB, as different allelic configurations lead to differing drug resistance levels, often rendering drugs ineffective
Setting research priorities for sexual and reproductive health in humanitarian settings: a global, stakeholder-informed agenda
Get PDFBackground: Sexual and reproductive health and rights (SRHR) remain critically underfunded and underresearched in humanitarian settings. Existing global research agendas are outdated, lack an implementation focus and often exclude perspectives from frontline practitioners. This exercise aims to identify and rank actionable research priorities globally and by region. Methods: We conducted a cross-sectional global, multiphase prioritisation exercise with information from frontline practitioners. The process included a scoping review and 11 regional consultations (informed by 91 SRHR experts), resulting in a long list of 101 SRHR research needs. Using these, we systematically listed and refined the SRHR research questions. A budget-weighted research prioritisation (BWRP) method was used for a global, multilingual survey to score 73 SRHR implementation questions across nine SRHR topical domains and three crosscutting domains. Domains were weighted equally, and regional priorities were identified. Results: A total of 271 experts contributed to the prioritisation ranking. Themes prioritised within the domains included the delivery of community-based care, self-care strategies, the integration of mental health into SRHR services and the improvement of adolescent access to contraception. A strong consensus emerged on the need to research topics such as human papilloma virus (HPV) vaccination, emergency obstetric and newborn care, and resilient SRHR service delivery amid climate shock. Substantial regional variation underscores the need for locally contextualised agendas, e.g., Europe and Central Asia prioritised quality of care and noncommunicable disease integration, whereas Latin America and the Caribbean emphasised gender-transformative approaches and community leadership. Conclusion: This stakeholder-informed research agenda responds to calls for context-specific SRHR research in humanitarian settings. The importance of tailoring research to local realities, including health system capacity, legal constraints and cultural norms, was a recurrent theme across all regions. The BWRP method enables clear prioritisation while reducing respondent burden, offering a practical model for future exercises. As global funding for SRHR contracts, aligning research with frontline needs is critical to ensuring effective, equitable service delivery
Cobamide metabolism, regulation, and adaptation in Mycobacterium tuberculosis.
Get PDFCobamides play a paradoxical but critical role in the biology of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although Mtb retains nearly all cobalamin (Cbl) biosynthetic genes and encodes multiple cobamide-requiring enzymes, experimental evidence indicates that Mtb is incapable of de novo Cbl synthesis under any tested conditions to date. Instead, an evolutionary shift appears to have occurred toward host dependency for biologically relevant cobamides or their precursors. This review highlights recent advances in our understanding of cobamide-related metabolism in Mtb, including: (i) the progressive erosion of de novo cobamide biosynthetic capacity across Mtb lineages; (ii) the role of host-derived cobamides in sustaining key mycobacterial metabolic pathways, including methionine synthesis and propionate catabolism; (iii) the impact of host immune pressures, including itaconate-mediated inhibition of methylmalonyl-CoA mutase; (iv) strategies employed by Mtb for cobamide and precursor acquisition; and (v) unique adaptations of Cbl-sensing riboswitches that regulate methionine synthesis, virulence-associated gene expression, and dormancy resuscitation. We also highlight unresolved questions, including possible niche-specific synthesis, utilization of alternate cobamide species, and the therapeutic potential of targeting cobamide-related metabolism. We review recent evidence of the centrality of cobamides in the metabolic flexibility of Mtb, virulence, and survival in the host environment, despite apparent loss of de novo biosynthetic capacity. Further mechanistic studies are required which may reveal vulnerabilities for the exploitation of cobamide acquisition, cobamide-related regulation, and the role of cobamides at the Mtb-host interface for innovative therapeutic interventions