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Unmet need for contraceptives and unintended pregnancies among adolescent girls and young women aged 15 to 24 in Zambia: insights from the Yathu Yathu trial.
BACKGROUND: In Sub-Saharan Africa, unmet need for contraceptives often remains high among adolescent girls and young women (AGYW), leading to unintended pregnancies. Yathu Yathu, a cluster-randomised trial of a community-based intervention conducted in two communities in Lusaka, Zambia (2019-2021), aimed to provide sexual and reproductive health services, including contraceptive services, to adolescents and young people. The trial showed no impact on pregnancy related outcomes. Hence, this analysis examined the characteristics of AGYW aged 15-24 with an unmet need for modern contraceptives and who experienced an unintended pregnancy. We also explored access to and reach of contraceptive services through Yathu Yathu.
METHODS: Secondary analysis of Yathu Yathu endline survey data. Using logistic regression, adjusted for cluster, we explored factors associated with unmet need for modern contraceptives and unintended pregnancies among AGYW in the intervention arm and assessed whether these associations differed in the control arm. Using routinely collected service delivery data from the intervention arm, numbers of AGYW accessing hormonal contraceptive services were described by age, community, educational attainment, and marital status.
RESULTS: In the intervention arm, 395 AGYW ever had sex. Unmet need for modern contraceptives was 40.6% (101/249) among AGYW who had sex in the last 12 months and wished to prevent or space childbearing. Unmet need was higher among younger and single/never married AGYW; in control zones unmet need was additionally higher among those currently in school or with infrequent discussion about sexual health promotion with their sexual partners. Among AGYW ever having had sex, 42.1% (165/392) reported an unintended pregnancy. This was higher among AGYW aged 20-24 years and currently not in school, and additionally among those in control zones who reported food absence. According to the routinely collected data, 12.3% (859/7005) of AGYW in intervention zones initiated hormonal contraceptives; 53.6% (460/859) returned for refills. Uptake was higher among AGYW aged 20-24, residing in community 2, with no/primary education and being married/cohabiting (p < 0.001).
CONCLUSIONS: This study highlights persistent challenges in addressing unmet need for modern contraceptives and unintended pregnancies among AGYW, emphasising the need for targeted interventions to improve equitable access among younger and single/never married AGYW.
TRIAL REGISTRATION: NCT04060420; https://clinicaltrials.gov/ct2/show/NCT04060420 ; and ISRCTN75609016. Registration date: 2019-08-12
Implementation and effects of social protection programs for children, older adults, and people with disabilities in Brazil and Ecuador: A scoping review.
We conducted a scoping review to investigate planned (intentional) and unplanned (not intentional) effects of social protection on socioeconomic determinants of health (SDH) and health inequalities among children, adolescents, elders and people with disabilities, and their caregivers. We reviewed seven programs in (i) Brazil (Programa Bolsa Familia (BFP) and Beneficio de Prestacao Continuada (BPC)), and (ii) Ecuador (Bono de Desarrolo Humano (BDH), Bono 1000 días, Pensión Mis Mejores Años/Pensión para Adultos Mayores, Pensión Toda una Vida/Pensión para personas con discapacidad and Bono Joaquín Gallegos Lara). We searched PubMed, EMBASE, LILACS, Scopus, Econlit, PsycINFO, Global Health, Global Index Medicus and grey literature for studies evaluating program implementation and effects on health outcomes or SDH from 1990 to 2023. We extracted data from 114 studies (84 on BFP, 17 on BDH and 13 on BPC). No studies were identified for the remaining programs. In Brazil, we found substantial evidence of BFP planned effects on children's health and some SDH but little evidence on its unplanned effects in adults and caregivers. Evidence effects of BPC on health outcomes were scarce, with only one study in elders and none among people with disabilities. In Ecuador, we found evidence only for BDH, with some studies on planned health effects and few on SDH and its unplanned effects. Very few studies used longitudinal data, quasi-experimental designs, or comparison groups of eligible non-recipients. Finally, we found large variations coverage and implementation of programs. In summary, our review highlights the lack of evidence on the overall impacts of social protection in Ecuador, particularly those targeting older adults and people with disabilities. In Brazil, further research is needed on unplanned health effects of the BFP and on the impacts of social protection targeting elders and people with disabilities
Validation of high-throughput oxford nanopore technology for HIV-1 transmitted/founder virus identification.
HIV-1 Transmitted/Founder (T/F) viruses cause 80-90% of heterosexual transmissions, making their rapid identification vital for vaccine and cure development. Single-genome amplification (SGA) followed by Sanger sequencing is the gold standard for T/F virus detection, but low throughput and high cost limit its scalability. Here, we evaluated the Oxford Nanopore Technology (ONT) as a high-throughput alternative. We sequenced 195 archived HIV-1 single genome amplicons (SGAs) from 20 acutely infected participants, encompassing both 3' and 5' genome halves. Libraries were prepared via end repair, native barcoding, and adapter ligation, and then sequenced on a MinION MK1C device with R9.4 flow cells. Data processing included read filtering, error correction, and haplotype reconstruction. T/F viruses were identified using Highlighter plots and by applying a criterion of intra-patient mean pairwise diversity <0.60%, together with phylogenetic clustering. The sequence most closely related to the most recent common ancestor (MRCA) was designated as the T/F virus. Phylogenetic analysis showed strong concordance between ONT and Sanger sequences, with 100% bootstrap support. ONT identified 35 of 39 T/F viruses detected by Sanger, achieving 89.70% sensitivity. Sequence similarity between ONT and Sanger - derived T/Fs averaged 99.81% (95% CI: 99.76-99.87%), ranging from 99.45-99.96%. These findings demonstrate ONT's promise as a reliable, high-throughput alternative for HIV-1 T/F identification. Advances such as the Dorado basecaller and Q20+ chemistry are expected to further improve ONT's accuracy, supporting its use in large-scale, resource-limited settings
Tracking dietary shifts towards lower carbon footprint in Italian households: a longitudinal analysis
Delivery of care in high mortality hospital settings: a direct observational study examining 1848 h of neonatal nursing in Kenya.
BACKGROUND: In resource-constrained countries, deploying better technologies is expected to improve neonatal care but little attention has been paid to the critical role of nurse staffing. We investigate nursing workloads and their relationship with care provision in recently upgraded Kenyan neonatal units. METHODS: We conducted a cross-sectional analysis using data from direct bedside observations across 8 intermediate-level neonatal units (defined by the World Health organization (WHO) as neonatal units capable of providing specialised but not intensive neonatal care) in Kenya over a 6-week period between February and March 2022. We excluded babies who were so severely ill that they were at risk of imminent death or transfer to a critical care facility and babies with congenital anomalies and surgical conditions. We used a structured observation checklist that had undergone content and face-validity testing in Kenya to collect workload and nursing care provision data. We determined nursing hours per patient per 12-h shift to measure nursing workload (primary exposure variable) and used a composite measure, the nursing care index (NCI), to score the nursing care delivered to a baby (primary outcome variable). The relationship between nursing workload and nursing care provision was assessed using multilevel models. FINDINGS: Across 8 hospitals spanning 1848 h of observation of 597 sick newborns, the median nursing time available for each newborn ranged from 19.2 to 72.0 min on a 12-h shift. Nurses delivered 32% of expected care, completely missed 32%, and informally delegated 36% of tasks. Unsupervised nursing students and mothers played prominent roles in the care of clinically unstable babies. An exploratory model combining qualified nurse and nursing student hours, that considerably expanded the range of the nursing workload metric, demonstrated a 3.1% increase in nurse-delivered care per additional 60 min of nursing time per baby per shift (β: 0.031, 95% CI: 0.019-0.043). INTERPRETATION: The nursing time available to care for sick newborns in Kenya is inadequate resulting in suboptimal care quality. Improving care quality, reducing of newborn mortality and making effective use of new technologies may not be possible without increasing nurse staffing in resource-constrained countries. FUNDING: National Institute for Health and Care Research
Frequency of tuberculosis symptoms at repeat visits amongst adults attending for HIV care in Gauteng province, South Africa.
BACKGROUND: Intensified tuberculosis (TB) case finding is recommended for people living with HIV (PLHIV) at every clinical encounter using the World Health Organization (WHO) screening tool (W4SS), comprising any of current cough, fever, night sweats or weight loss. We determined the frequency of W4SS symptoms at repeat visits among individuals without TB attending for HIV care in Gauteng province, South Africa. METHODS: In a cohort study, we enrolled PLHIV (adults) attending clinics for routine HIV care. At enrolment, patients were screened using W4SS, and categorised into high (cough, body mass index (BMI) ≤ 18.5, CD4 < 100 cells/mm3, fever ≥ 3 weeks, and unintentional weight loss ≥ 10%), medium (1 ≥ W4SS symptoms but not fulfilling criteria for high priority) or low priority (no W4SS symptoms) for TB testing with Xpert MTB/RIF; and anyone diagnosed with TB was excluded. This analysis was restricted to individuals with no TB diagnosis by month three. RESULTS: We enrolled 3,738 patients in the parent study. Of this, 88.5% (3,309/3,738) completed month three follow up visits, of whom 71.0% (2,349/3,309) were female, median CD4 count 427 [interquartile range (IQR) 275-607] cells/mm3, 71.8% (2,377/3,309) on antiretroviral therapy (ART) with median duration 4 [IQR 2-7] years). At enrolment, 29.9% (991/3,309) were positive on W4SS, among whom 62.7% (621/991) were pre-ART. The proportion of patients who reported any of the four symptoms on W4SS was 15.1% (331/2,191) at month one, 13.5% (276/2,052) at month two, and 8.9% (294/3,309) at month three. Cough was the symptom most frequently reported at all time points, followed by weight loss and then night sweats. CONCLUSION: W4SS symptoms remained relatively common at repeat visits among people without TB in HIV care. Repeat testing of symptomatic patients with Xpert MTB/RIF would have substantial resource implications. Sensitive and specific TB screening tools which are not dependent on symptoms are needed
Sand fly saliva reprograms skin fibroblasts to enhance arbovirus infection.
Arbovirus transmission by sand flies is a growing public health concern, yet the early skin events shaping infection outcomes remain undefined. We establish a mouse model of Toscana virus (TOSV) infection that incorporates sand fly salivary factors to mimic natural transmission. Saliva from two distinct sand fly genera significantly enhanced infection and promoted neurological signs and joint inflammation, recapitulating key features of human TOSV disease. In the skin, dermal macrophages and fibroblasts were the main infected cell types, but only fibroblasts generated infectious virus. Saliva reprogrammed fibroblasts into a wound-healing state permissive to viral replication, driving local viral amplification, systemic spread, and thereby clinical disease. These findings identify skin fibroblasts as central determinants of host susceptibility and reveal that sand fly saliva actively remodels the skin to exacerbate viral pathogenesis. This work redefines the skin's role in sand fly-transmitted infection and highlights new targets for therapeutic and vaccine development
Nomenclature, definitions, and methodological approaches to estimate the association between antimicrobial treatment and clinical outcomes of drug-resistant bloodstream infections.
BACKGROUND: Antimicrobial resistance increases the risk of misaligned initial antibiotic treatment (IAT), as susceptibility data are typically delayed. The causal effect on patient outcomes, however, is unclear due to reliance on observational studies with methodological heterogeneity. OBJECTIVES: To describe the terminology and definitions for IAT misalignment and evaluate methods used to analyse its association with mortality and hospital length of stay (LOS) for patients with drug-resistant bloodstream infections (BSIs). METHODS: A systematic review. DATA SOURCES: PubMed and EMBASE: January 1990 to August 2024. STUDY ELIGIBILITY CRITERIA: We included studies on drug-resistant BSIs caused by ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and other Enterobacterales). Eligible studies defined IAT misalignment and assessed its effect on mortality/LOS. PARTICIPANTS: Patients with drug-resistant BSIs. EXPOSURE: (mis)aligned IAT. ASSESSMENT OF RISK OF BIAS: Revised versions of the Joanna Briggs Institute tools. METHODS OF DATA SYNTHESIS: Qualitative synthesis. RESULTS: From 3627 screened publications, 187 studies were included, predominantly cohort studies (n = 183). The most common terminology for IAT misalignment was "(in)appropriate" (n = 139, 74.3%), followed by "(in)adequate" (n = 34, 18.2%). Definitions primarily considered in vitro susceptibility to prescribed antibiotic(s) (n = 184, 98.4%), with up to nine additional criteria. Impact of (in)appropriate IAT on mortality (n = 186) was mostly evaluated using logistic or Cox regression, including various confounder selection methods, showing an association in 122 of 186 studies (65.6%). Admission-to-infection time and infection-to-treatment time were rarely considered. Impact of (in)appropriate IAT on LOS was shown in two of nine studies. Only four studies explicitly analysed postinfection LOS. No study scored a low risk of bias, due to residual confounding and time-dependent bias. DISCUSSION: Wide variability of IAT definitions and impact analysis was observed, with a high risk of bias, hindering data aggregation and limiting understanding of the causal effect of inappropriate IAT on clinical outcomes. Guidelines are required to improve study quality and harmonize future research
Improved global air quality health index reveals ozone and nitrogen dioxide as main drivers of air-pollution-related acute mortality.
Ambient air pollutants are leading contributors to global mortality. Despite the well-established risks, most studies have relied on single-pollutant models in limited regions, leaving the combined effects and individual contributions of pollutants unclear, particularly across countries. Here, we integrate daily mortality and air pollutant (nitrogen dioxide [NO2], ozone [O3], fine particulate matter, and sulfur dioxide) data from 482 cities in 12 countries/territories from 1998 to 2021 to assess the joint mortality risks and identify the main contributing pollutant through an air quality health index of multi-pollutant constrained groupwise additive models (AQHI-Multi). AQHI-Multi outperformed commonly used air quality indices in capturing the overall mortality risks. O3 and NO2 were the leading contributors (accounting for over 70% across countries/territories), with O3's share increasing slightly to moderately in most countries/territories. These findings highlight the need for developing air quality indices using advanced multi-pollutant models and the emerging global significance of targeted control of O3 and NO2
Impact of fluoroquinolone resistance on the cost-effectiveness of empiric treatment for multidrug- or rifampicin-resistant tuberculosis.
The WHO recommends the bedaquiline, pretomanid, and linezolid (BPaL) regimen with the additional fluoroquinolone antibiotic moxifloxacin (BPaLM) for initial treatment of multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB). However, fluoroquinolone drug susceptibility testing (DST) coverage for MDR/RR-TB is only around 55% globally, and the efficacy of moxifloxacin may be compromised in settings with high fluoroquinolone resistance. We extended a previous Markov cohort model to assess the cost-effectiveness of the empirical use of BPaLM as a replacement for BPaL for the treatment of MDR/RR-TB in four high MDR/RR-TB burden countries. We obtained fluoroquinolone resistance rates in these countries from WHO surveillance data and parameterised treatment efficacy from recent trial results. We performed scenario analyses across varying fluoroquinolone resistance prevalence and performed Monte Carlo simulations to generate uncertainty intervals for our primary cost-effectiveness estimates. BPaLM incurred higher costs than BPaL but averted more disability-adjusted life years, with incremental cost-effectiveness ratios below 50% of each country's 2019 GDP per capita. This finding remained robust across a feasible fluoroquinolone resistance prevalence range (0-70%). In the absence of fluoroquinolone DST, empirical use of BPaLM resulted in 49-32 (IQR: 53), 28 - 174 (IQR: 209) per DALY averted in Georgia, India, the Philippines, and South Africa respectively. Our findings support the empirical use of BPaLM as a potential replacement for BPaL for the treatment of MDR/RR-TB in the absence of fluoroquinolone DST, even if fluoroquinolone resistance prevalence were to increase, reinforcing recent WHO recommendations