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A registry-based retrospective study comparing pre-dialysis care and early outcomes in native vs transplant kidney failure.
Get PDFBACKGROUND: Starting dialysis is associated with morbidity and mortality. Outcomes for people with failed transplants can be poorer than for people with native kidney failure. We aimed to determine whether dialysis modality, place of initiation and mortality outcomes differed in the first 90 days between people starting dialysis for transplant and native kidney failure. METHODS: Retrospective cohort using linked UK Renal Registry data and Hospital Episode Statistics. Modality, place of initiation and outcomes compared with Day 90 for 16 417 adults starting dialysis in England between January 2018 and December 2019. RESULTS: Relative to those with native kidney failure (90.6%), those with transplant failure (9.4%) were younger (median 55.2 vs 66.3 years) and commenced more in-centre haemodialysis [86.8% vs 82.2%, adjusted odds ratio (OR) 1.72, 95% confidence interval (CI) 1.47-2.01; P < .0001]. Compared with individuals reported to have native chronic kidney disease, and accounting for age, sex, diabetes and ethnicity, those with transplant failure had increased odds of starting dialysis in hospital (adjusted OR 2.26, 95% CI 1.84-2.76; P < .0001), at higher estimated glomerular filtration rates (eGFRs) (8.9 vs 7.9 mL/min/1.73 m²; P = .0001), and death [adjusted OR 1.95, 95% CI 1.31-2.90; P = .001). DISCUSSION: UK patients starting dialysis for transplant failure do so at higher eGFRs than those receiving specialist chronic kidney disease care. Those with transplant failure appear disproportionately likely to start as inpatients, receive haemodialysis or die within 90 days. These findings are likely to reflect differences between both patient groups and care pathways. Deeper understanding may inform improvements in care
Adherence to Perinatal Asphyxia or Sepsis Management Guidelines in Low- and Middle-Income Countries.
Get PDFIMPORTANCE: Most of the 2.3 million annual neonatal deaths occur in sub-Saharan Africa and South Asia, with perinatal asphyxia and neonatal sepsis being the leading causes of neonatal mortality. Most neonatal deaths are considered preventable through high-quality clinical care, which includes adherence to clinical care guidelines. OBJECTIVE: To assess adherence to World Health Organization clinical care guidelines for management of perinatal asphyxia and neonatal sepsis and to identify patient-level factors in adherence among neonates who died from these conditions. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study obtained data from December 2015 through October 2023 from the Child Health and Mortality Prevention Surveillance (CHAMPS) catchment areas in 7 low- and middle-income countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and South Asia (Bangladesh). Participants were neonates who were born alive and were aged 0 to 28 days at the time of death and had either perinatal asphyxia or neonatal sepsis. EXPOSURE: Medical records of neonates who died from perinatal asphyxia or neonatal sepsis determined by postmortem diagnostics. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of deceased neonates who received guideline-adherent treatments before they died. Mixed-effect multivariable logistic regression analyses were performed to identify factors associated with administration of at least bag-valve-mask (BVM) ventilation for perinatal asphyxia. RESULTS: Of the 1194 neonates (median [IQR] age at the time of death, 2 [1-6] days; 692 males [58.0%]) who died and were enrolled in CHAMPS with available clinical data, 476 (39.9%) died from perinatal asphyxia, 562 (47.0%) died from neonatal sepsis, and 156 (13.1%) from both conditions. These neonates had a median (IQR) birth weight of 2130 (1266-2988) g. For cases with perinatal asphyxia, guideline adherence ranged from 12.2% (n = 77) for adrenaline administration to 85.4% (540) for supplemental oxygen administration. Only 4.4% of neonates (28) with perinatal asphyxia received all recommended treatments. Among cases with neonatal sepsis, antibiotics were administered to 86.8% (623), although the recommended treatment was administered to only 61.0% (438). In multivariable analyses, neonates in whom clinicians accurately identified perinatal asphyxia were more likely to receive BVM ventilation than those who had received discordant antemortem and postmortem diagnoses (adjusted odds ratio, 2.00; 95% CI, 1.29-3.12). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, clinical care guideline adherence was suboptimal among neonates who died from perinatal asphyxia or neonatal sepsis. This finding underscores the critical need to increase adherence in regions with high rates of neonatal mortality and may inform strategies for strengthening health systems to support compliance with clinical care guidelines
HIV-1 Gag-protease-driven replicative capacity influences T-cell metabolism, cytokine induction, and viral cell-to-cell spread.
Get PDFHigh replicative capacity (RC) HIV-1 strains are associated with elevated viral loads and faster disease progression in the absence of antiretroviral therapy. Understanding the mechanisms by which high RC strains adversely affect the host is essential for developing novel anti-HIV interventions. This study investigates cellular metabolism, cytokine induction, and cell-to-cell spread as potential mechanisms differentiating clinical outcomes between low and high RC strains of HIV-1. We constructed chimeric viruses containing patient-derived gag-proteases from HIV-1 subtypes B and C in the NL4-3 backbone. Viral RC was determined using a green fluorescent protein (GFP)-reporter T-cell line assay and cytokine production in T-cells was assessed using Luminex. Virus cell-to-cell spread efficiency was measured through flow cytometry-based detection of p24, while nutrient uptake assays and mitotracker dye detection served as surrogate markers for T-cell metabolism and mitochondrial function. Chimeric subtype C viruses exhibited significantly lower RC compared to subtype B viruses (P = 0.0008). Cytokine profiling revealed distinct cytokine signatures associated with low RC subtype C viruses. Viral RC negatively correlated with tumor necrosis factor alpha (TNF-α), IL-8, and IL-13 induction, while it positively correlated with platelet-derived growth factor (PDGF-bb), IL-7, monocyte chemoattractant protein-1 (MCP-1), fibroblast growth factor (FGF)-basic levels, viral spread efficiency (P = 0.008, r = 0.5), and cellular glucose uptake (P = 0.02, r = 0.5). Conversely, RC was negatively correlated with glutamine levels (P = 0.001, r = -0.7), indicating a link between RC and nutrient utilization. Furthermore, mitochondrial depolarization was elevated in subtype B infections when compared to subtype C infections (P = 0.0008). These findings indicate that high RC strains exert distinct cellular effects that may influence HIV-1 pathogenesis, highlighting the need to develop novel therapeutic strategies.IMPORTANCEVirus replicative capacity (RC) influences disease progression following HIV-1 transmission; however, the mechanisms underlying the differential clinical outcomes remain poorly understood. Our study reveals variations in cytokine induction and cellular metabolism in T-cells infected with HIV-1 subtype B and C viruses exhibiting high or low RC. T-cells infected with high RC strains showed increased induction of IL-7 and platelet-derived growth factor (PDGF-bb), along with heightened glucose uptake and elevated glutamine consumption compared to those infected with low RC strains. By contrast, low RC strains induced higher levels of IL-8, IL-13, and tumor necrosis factor alpha (TNF-α) and demonstrated reduced efficiency in modulating cellular metabolism and virus cell-to-cell spreadability. These findings highlight distinct biological differences between high and low RC viruses, providing valuable insights into the mechanisms that may underpin varying clinical outcomes. This knowledge may inform the development of novel interventions aimed at limiting viral virulence or transmission
Contemporary digital marketing techniques used in unhealthy food campaigns targeting young people.
Get PDFThe digital marketing of unhealthy foods and non-alcoholic beverages has a detrimental impact on children's eating behaviours, leading to adverse diet-related health outcomes. To inform the development of evidence-based strategies to protect children online, this study aimed to describe contemporary digital marketing techniques and industry reported impacts from unhealthy food and beverage marketing campaigns aimed at young people aged 3-17. We conducted a qualitative conceptual content analysis of 111 industry reports detailing the nature and impact of unhealthy food and beverage marketing campaigns from around the world that directly or indirectly targeted children through digital channels. We categorised and narratively describe how food and beverage companies are using digital marketing techniques, across four conceptual groups: (i) leveraging data and technology to optimise marketing, (ii) profiling and segmenting audiences, (iii) targeting and personalisation, and (iv) generating participation and engagement. Industry reported impacts on young people as a result of campaigns included i) increased exposure to, and engagement with, unhealthy food marketing, ii) purchases and consumption of unhealthy foods and beverages iii) formation of emotional brand connections and enhanced future marketing through data collection. Our findings support and extend existing literature revealing how multinational food and beverage companies are using advanced digital marketing techniques, including artificial intelligence and new technologies, to shape children's food behaviours and influence their diets worldwide. Policy actions are needed to protect children from the sophisticated digital marketing techniques used by the food and beverage industry
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: This study aims to investigate the association among coprescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality. METHODS: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011 to March 29, 2021. We used a cohort design to estimate hazard ratios (HRs) 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 with different drug initiation patterns for all outcomes in hazard window vs referent window within an individual was also conducted. RESULTS: Of 483,815 DOAC users, we identified 21,701 coprescribed clarithromycin, 4532 coprescribed erythromycin, and 4840 coprescribed fluconazole. We observed an increased risk of gastrointestinal bleeding over 7 days following coprescription of DOAC + erythromycin vs DOAC alone (HR 3.66; 99% confidence interval [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 DOACs. 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
Longitudinal Trends in Physical Activity Among Older Adults With and Without HIV in Uganda.
Get PDFIntroductionPhysical Activity (PA) and its links to frailty, quality of life (QoL), and other comorbidities in older Ugandans living with HIV remain under-explored.MethodsWe analyzed data from three annual assessments of older people living with HIV (PLWH) and age- and sex-similar people not living with HIV (PnLWH). We fitted linear generalized estimating equations (GEE) regression models to estimate the correlates of PA, including demographics, frailty, QoL, HIV, and other comorbidities.ResultsWe enrolled 297 PLWH and 302 PnLWH. Older age (b = -157.34, 95% CI [-222.84, -91.83]), living with HIV (b = -979.88 [95% CI: -1878.48, -81.28]), frailty (b = -3011.14 [95% CI: -4665.84, -1356.45]), and comorbidities (b = -2501.75 [95% CI: -3357.44, -1646.07]) were associated with lower overall PA. Higher general QoL (b = 89.96 [95% CI: 40.99, 138.94]) was associated with higher PA.ConclusionPA interventions may support wellbeing of older people in the region, and tailored interventions should be explored
Emerging models to study competitive interactions within bacterial communities.
Get PDFWithin both abiotic and host environments, bacteria typically exist as diverse, multispecies communities and have crucial roles in human health, agriculture, and industry. In these communities, bacteria compete for resources, and these competitive interactions can shape the overall population structure and community function. Studying bacterial community dynamics requires experimental model systems that capture the different interaction networks between bacteria and their surroundings. We examine the recent literature advancing such systems, including (i) in silico models establishing the theoretical basis for how cell-to-cell interactions can influence population level dynamics, (ii) in vitro models characterizing specific interbacterial interactions, (iii) organ-on-a-chip models revealing the physiologically relevant parameters, such as spatial structure and mechanical forces, that bacteria encounter within a host, and (iv) in vivo plant and animal models connecting the host responses to interbacterial interactions. Each of these systems has greatly contributed to our understanding of bacterial community dynamics and can be used synergistically to understand how bacterial competition influences population architecture
Identifying barriers and potential solutions to improve equitable access to community eye services: an exploratory sequential mixed methods study protocol.
Get PDFINTRODUCTION: Access to care varies by sociodemographic group, with some groups facing higher barriers to care than others. This study will use novel methods to explore barriers and potential solutions as perceived by members of the population groups who are least able to access care. We aim to use rapid yet robust mixed methods that allow us to identify generalisable findings within each programme and testable service modifications to improve equitable access to care; delivering non-tokenistic findings within a matter of weeks. METHODS AND ANALYSIS: This is a multiphased exploratory sequential mixed methods study. We will use the same approach in four different screening programmes, in Botswana, India, Kenya and Nepal. First, we will conduct interviews with people purposively selected from the sociodemographic subgroups with the lowest odds of accessing care within each programme. We will explore their perceptions of barriers and potential service modifications that could boost attendance at eye clinics among people from these 'left-behind' groups. We will use a deductive analytic matrix to facilitate the rapid analysis of qualitative data. Space will be made for the inductive identification of themes that are not necessarily captured in the framework. Sample size will be determined by thematic saturation. Next, we will conduct a survey with a representative sample of non-attenders from the same left-behind groups, asking them to rank each suggested service modification by likely impact. Finally, we will convene a multistakeholder workshop to assess each service modification based on ranking, likely impact, feasibility, cost and potential risks. The most promising service modifications will be implemented and evaluated in a follow-on randomised controlled trial, the methods for which will be reported elsewhere. ETHICS AND DISSEMINATION: This project has been approved by independent research ethics committees in Botswana, Kenya, India, Nepal and the UK. We will disseminate our findings through local community advisory boards, national eye screening meetings, in peer-reviewed journals and at conferences
Clinical Characterization and Outcomes of Human Clade IIb Mpox Virus Disease: A European Multicenter Mpox Observational Cohort Study (MOSAIC).
Get PDFBACKGROUND: The global mpox outbreak that started in May 2022 was caused by a novel clade IIb variant of the mpox virus (Orthopoxvirus monkeypox, MPXV). It differed from the traditional Western and Central Africa disease in transmission patterns and clinical presentation. METHODS: To address the need for detailed clinical and virologic data, we conducted an observational cohort study (MOSAIC) during May 2022-July 2023 in individuals with confirmed MPXV infection enrolled in 6 European countries. Case management decisions were left to the attending physician. Participants were monitored for up to 6 months for clinical signs/symptoms and clinical and virologic outcomes through hospital visits, phone interviews, and self-administered questionnaires. Outcomes included time to lesion resolution, clinical status, and virus clearance. RESULTS: The 518 participants not receiving any specific treatment ("untreated") were diagnosed a median 5 days from symptom onset; 90% were managed as outpatients. Lesions were mostly cutaneous (88%) and perigenital (74%). By day 14 from the first polymerase chain reaction (PCR)-positive sample, 39% had resolved lesions. Time to 95% unculturable virus was longest in cutaneous lesions (52 days). A putative systemic antiviral was available for 57 participants, 44% as inpatients; 34% and 58% had resolved lesions by day 14 from the first PCR-positive sample and from treatment start, respectively. Time to 95% unculturable virus was 60 days in skin and oropharynx. No death or recrudescence occurred by day 180. CONCLUSIONS: MOSAIC provides comprehensive insights into the clinical and virologic characteristics of mpox caused by the clade IIb variant. The study forms the basis of clinical characterization for ongoing mpox outbreaks
Estimating future heat-related and cold-related mortality under climate change, demographic and adaptation scenarios in 854 European cities.
Get PDFPrevious health impact assessments of temperature-related mortality in Europe indicated that the mortality burden attributable to cold is much larger than for heat. Questions remain as to whether climate change can result in a net decrease in temperature-related mortality. In this study, we estimated how climate change could affect future heat-related and cold-related mortality in 854 European urban areas, under several climate, demographic and adaptation scenarios. We showed that, with no adaptation to heat, the increase in heat-related deaths consistently exceeds any decrease in cold-related deaths across all considered scenarios in Europe. Under the lowest mitigation and adaptation scenario (SSP3-7.0), we estimate a net death burden due to climate change increasing by 49.9% and cumulating 2,345,410 (95% confidence interval = 327,603 to 4,775,853) climate change-related deaths between 2015 and 2099. This net effect would remain positive even under high adaptation scenarios, whereby a risk attenuation of 50% is still insufficient to reverse the trend under SSP3-7.0. Regional differences suggest a slight net decrease of death rates in Northern European countries but high vulnerability of the Mediterranean region and Eastern Europe areas. Unless strong mitigation and adaptation measures are implemented, most European cities should experience an increase of their temperature-related mortality burden