A retrospective study of HIV antiretroviral treatment persistence in a commercially insured population in the United States

This study examined factors associated with persistence (time from initiation to discontinuation of treatment) on initial antiretroviral (ARV) therapy in commercially insured HIV patients in the United States, a population not well researched. This retrospective analysis of US health insurance claims data from 1 January 2003 to 30 June 2008 included treatment-naive patients aged 18–65 years with an HIV diagnosis receiving ARV therapy consisting of at least two individual nucleoside reverse transcriptase inhibitors (NRTIs) or one fixed-dose combination NRTI, plus at least one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor (PI), with or without ritonavir. Descriptive statistics, Kaplan-Meier survival estimation, and Cox proportional hazards regression models were completed. Patients were considered persistent until any component of the regimen was modified or there was a gap in treatment > 90 days. A total of 2460 patients met full inclusion criteria (1388 NNRTI and 1072 PI). Mean (SD) time to discontinuation for NNRTI- vs PI-based regimens was 370 (346) vs 295 (338) days (p < 0.001). Female sex, substance use, low comorbidity score, index year before 2007, geographical region, and taking a lopinavir/ritonavir regimen predicted discontinuation. Relative to NNRTI-based regimens, PI-based regimens demonstrated a greater risk of discontinuation (hazard ratio [HR], 1.32; p <0.001). The fixed-dose efavirenz/emtricitabine/tenofovir combination yielded the lowest risk of discontinuation (HR, 0.39; p < 0.001). HIV treatment persistence was longer with NNRTI-based regimens than PI-based regimens. The fixed-dose regimen of once-daily efavirenz/emtricitabine/tenofovir had the lowest risk of discontinuation

Effectiveness of introducing pulse oximetry and clinical decision support algorithms for the management of sick children in primary care in Kenya and Senegal on referral and antibiotic prescription: the TIMCI quasi-experimental pre-post study.

Acute illnesses are leading causes of death among children under-five, who often receive antibiotics unnecessarily, contributing to antimicrobial resistance. Pulse oximetry and digital Clinical Decision Support Algorithms (CDSAs) can strengthen the detection and management of severe childhood illnesses, and support antibiotic stewardship in primary care, but lack evidence for scale-up. This study sought to understand the real-world impact of these tools on urgent referrals and antibiotic prescription for children under-five. A quasi-experimental pre-post study of the implementation of pulse oximetry and CDSAs for healthcare providers (HCPs) managing sick children at primary care level was conducted in Kenya and Senegal. Sick children 0-59 months attending study facilities were eligible. Trained research assistants collected data from caregivers and facility records on Day 0, with a follow-up phone call at Day 7. Providers were advised to use pulse oximetry for all sick children in Kenya, and in Senegal for all 1-59 days, and for 2-59 months with cough or difficulty breathing, or a moderate to severe illness. Urgent referral was recommended for SpO &lt;sub&gt;2&lt;/sub&gt; &lt;90% in Kenya and SpO &lt;sub&gt;2&lt;/sub&gt; &lt;92% in Senegal. Primary outcomes were antibiotic prescription and urgent referral rates at Day 0. They were assessed using generalised estimating equations for logistic regression. Results were estimated in terms of odds ratios and risk differences (RDs), adjusted where computable. The study is registered with clinicaltrials.gov (NCT05065320). A total of 50,580 sick children (1-59 days: 979 pre, 1748 post; 2-59 months: 16,782 pre, 31,071 post) were enrolled from September 13, 2021 to February 8, 2023 in Kenya and August 16, 2021 to March 31, 2023 in Senegal. In the pre-intervention period, urgent referrals were rare (0.6% in 1-59 days; 0.4% in 2-59 months), while antibiotic prescriptions were common (53.9% in 1-59 days; 74.9% in 2-59 months). Intervention uptake was 75% in Kenya and 40% in Senegal where a protracted HCP strike affected the intervention. The prevalence of SpO &lt;sub&gt;2&lt;/sub&gt; values prompting an urgent referral recommendation was 1.3% in 1-59 days and 0.8% in 2-59 months, but few of them resulted in actual referrals (26.1% in 1-59 days; 11.4% in 2-59 months). There was no change in overall urgent referrals (RD 0.2% [-0.5%, 0.9%] in 1-59 days; adjusted RD 0.2% [-0.2%, 0.5%] in 2-59 months). Antibiotic prescription rate was reduced by 14.6% [8.7%, 20.6%] in 1-59 days and by 22.6% [18.3%, 26.9%] in 2-59 months in the post-intervention period while caregiver-reported recovery rates at Day 7 remained stable. When implemented in routine health systems at primary care level in Kenya and Senegal, pulse oximetry and CDSAs were not found to be associated with an increase in urgent referrals but likely mediated antibiotic prescription reductions. The absence of referral increase may stem from limited severe illness detection due to low hypoxaemia prevalence and barriers to referral, also affected in Senegal by a protracted post-intervention HCP strike. Strengthening the referral system and implementing broader antibiotic stewardship strategies are likely to be needed to improve the effectiveness of the intervention and its impact on child health outcomes. Unitaid grant n°2019-35-TIMCI: Tools for Integrated Management of Childhood Illness

Contribuição ao estudo da interrelação flúor-manganês em ratos

Devido a numerosas discrepâncias nos resultados de estudos experimentais relativos à interação flúor-manganês, propusemo-nos a verificar se a adição de manganês 5 água fluoretada (1 ppm), em diferentes proporções fluor-manganês, levaria a uma diferente fixaçao do halogênio. Para tanto, 24 ratos Wistar, recém-desmamados, foram mantidos em dieta padrão de caseína a 27%, recebendo na sua água de consumo: 1) H2O destilada (controle); 2) 1,0 ppm de flúor: 3) 1,0 ppm de flúor + 0,5 ppm de manganês (F:Mn = 2,0); 4) 1,0 ppm de flúor +1,0 ppm de manganês (F: Mn = 1,0). Foram anotados o peso ganho e o consumo de alimento e água, durante os 60 dias de experimento, após o qual as patas traseiras, dos animais sacrificados, foram autoclavadas e desossadas, e os femures retirados. Posteriormente, foram estes submetidos à secagem, extração da gordura, pulverização e analise do flúor fixado. Também foram efetuadas analises da composição centesimal da ração e de flúor e manganês nesta e nas diferentes águas de consumo. Os resultados de percentagem do flúor ingerido fixado nos femures, foram analisados estatisticamente pelo teste não-paramétrico de Kruskal-Wallis (níveis de 1% e 5%) mostrando que, para as proporções consideradas, o flúor na taxa de 1 ppm, o manganês, quando administrado após o desmame, parece não afetar a fixaçao do flúor. Contudo, faz-se necessário dar continuidade aos estudos com novas proporções e taxas mais elevadas de flúor e manganês.An experiment to determine the effects of varying the manganese concentration of the diet on the fluorine retention in the femur of rats was made. Four groups of weaning rats were fed ad libitum a 27% casein synthetic diet and were provided with water as follows: 1) distilled (control); 2) containing 1 ppm of fluorine (F); 3) 1,0 ppm F + 0,5 ppm Mn; 4) 1 ppm F + 1 ppm Mn. The weight gain and food and water consumption were measured during 60 days. The results indicated that manganese does not seem to affect the proportional fixation of fluorine in the femur. The authors think that more data should be available before a definite conclusion on the influence of the ratio F:Mn on the fluorine retention could be drawn

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

Enabling equitable and affordable access to novel therapeutics for pandemic preparedness and response via creative intellectual property agreements

The COVID-19 pandemic demonstrated that the current purely market-driven approaches to drug discovery and development alone are insufficient to drive equitable access to new therapies either in preparation for, or in response to, pandemics. A new global framework driven by equity is under negotiation at the World Health Organization to support pandemic preparedness and response. Some believe that the global intellectual property (IP) system itself is part of the problem and propose a purely Open Science approach. In this article, we discuss how existing IP frameworks and contractual agreements may be used to create rights and obligations to generate a more effective global response in future, drawing on experience gained in the COVID Moonshot program, a purely Open Science collaboration, and the ASAP AViDD drug discovery consortium, which uses a hybrid, phased model of Open Science, patent filing and contractual agreements. We conclude that ‘straight to generic’ drug discovery is appropriate in some domains, and that targeted patent protection, coupled with open licensing, can offer a route to generating affordable and equitable access for therapy areas where market forces have failed. The Extended Data contains a copy of our model IP policy, which can be used as a template by other discovery efforts seeking to ensure their drug candidates can be developed for globally equitable and affordable access

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries