Search Results for: Libro sugli antibiotici del WHO AWaRe (Access, Watch, Reserve)

Background
Despite global improvements in antiretroviral therapy (ART) access for children and adolescents living with HIV (CALHIV), a significant proportion continue to experience unsuppressed viral load (USVL). Limited studies focus on the factors contributing to USVL among CALHIV in the Democratic Republic of the Congo (DRC), especially in the context of evolving treatment landscapes. Understanding these determinants is crucial for enhancing ART outcomes.

Objective
This study aimed to determine the prevalence of USVL and identify factors associated with USVL among CALHIV receiving ART in Lubumbashi, DRC.

Design
A multicentre retrospective cross-sectional study was conducted. Data were gathered using an observational checklist based on assessing patient file data and entered into Microsoft Excel. Analysis was performed using STATA V.16. Variables with a p value of 0.20 from the bivariable analysis were included in a multivariable logistic regression model, and significant variables (p

Introduction
The COVID-19 pandemic amplified the need for robust multisectoral coordination; yet the specific mechanisms, benefits and challenges of such collaboration particularly in low- and middle-income countries (LMICs) remain poorly synthesised. This review aims to delineate the key elements, benefits, challenges and improvement strategies of multisectoral coordination during COVID-19 and to compare patterns between LMICs and high-income countries (HICs).

Methods and analysis
Eligible studies will include empirical qualitative, quantitative or mixed-methods research published in English between 1 January 2020 and 15 August 2024 that examines formal coordination mechanisms (eg, task forces, public-private partnerships, inter-agency committees) within the context of COVID-19. Searches will be conducted across PubMed, EBSCOhost, Emerald Insight, Google Scholar and selected grey-literature repositories. Citation chaining will be employed to identify additional sources.
Two reviewers will independently screen all records using Covidence, applying pre-piloted eligibility criteria to 5% of citations and proceeding only if inter-rater reliability achieves ≥0.70. Data will be extracted into a Consolidated Framework for Implementation Research (CFIR)-informed template. Qualitative data will be analysed through framework synthesis, structured by the five CFIR domains. Quantitative data will be narratively summarised and, where outcomes are sufficiently similar across at least two studies, synthesised using a fixed-effect model.
Risk of bias will be assessed using Critical Appraisal Skills Programme for qualitative and Risk Of Bias In Non-randomised Studies of Interventions for non-randomised studies. Studies with serious or critical risk will be excluded from pooling. Subgroup analyses (LMIC vs HIC), sensitivity analyses (model and risk) and confidence grading using Confidence in the Evidence from Reviews of Qualitative Research and Grading of Recommendations, Assessment, Development and Evaluations will be conducted.

Ethics and dissemination
No primary data will be collected; thus additional Research Ethics Committee approval is unnecessary. The results will be disseminated via open-access publication, conference presentations and policy briefs for Nairobi County health stakeholders.

PROSPERO registration number
CRD42023466849.

Introduction
The National Family Health Survey-5 has reported an under-five mortality rate of 41.9 per 1000 live births in India. Pneumonia, one of the leading causes of under-five mortality, contributes substantially to this figure. The Indian government has made efforts through multiple national programmes, but pneumonia-specific mortality remains high. The Government of India revised their Childhood Pneumonia Management Guidelines in 2019 to improve under-five pneumonia prevention and management. This implementation study aims to achieve a high population-based coverage of pneumonia treatment for under 5 yearold children in the Palwal district of India.

Method and analysis
This implementation study uses a quasi-experimental pre-post design and a mixed-methods approach, conducted in three phases: (i) formative research, (ii) model optimisation through iterative testing in a learning block and (iii) scale-up and concurrent evaluation. The study is set in Palwal district, Haryana, and the primary catchment/study area will be the Health and Wellness Centres, the most accessible public health facilities for the community. Approximately 4167 households will be surveyed to capture ~2400 under-five children, among whom about 120 pneumonia cases (based on an estimated 5% prevalence) will be included in the analysis of treatment coverage and outcomes. Quantitative data will be analysed using descriptive statistics and generalised linear models, while qualitative data from focus group discussions and in-depth interviews will be thematically analysed using NVivo software.

Ethics and dissemination
Ethical approval was granted by the ethical committees of the Society for Applied Studies (ERC/IR Pneumonia/2021), the Regional Ethics Committee of Western Norway (2022/531608) and the WHO(ERC.0003652). Additionally, this study has obtained the Government of Haryana state (Memo no. HSHRC/2022/505) and Health Ministry steering committee (approval date: 19 Dec 2022, proposal id 2022–17596) approvals. Informed consent will be obtained from all participants, including caregivers and healthcare workers, prior to data collection. Dissemination meetings in the study country will share results with stakeholders, including Ministry of Health officials, health managers, families of under-five children, community leaders and academia, to discuss national health programme implications. Results will also be shared regionally and globally, with publications and presentations encouraged in national and international forums.

Study registration
Clinical Trials Registry – India, CTRI/2021/03/031622.

Introduction
Histopathological evaluation of prostate biopsies using the Gleason scoring system is critical for prostate cancer diagnosis and treatment selection. However, grading variability among pathologists can lead to inconsistent assessments, risking inappropriate treatment. Similar challenges complicate the assessment of other prognostic features like cribriform cancer morphology and perineural invasion. Many pathology departments are also facing an increasingly unsustainable workload due to rising prostate cancer incidence and a decreasing pathologist workforce coinciding with increasing requirements for more complex assessments and reporting. Digital pathology and artificial intelligence (AI) algorithms for analysing whole slide images show promise in improving the accuracy and efficiency of histopathological assessments. Studies have demonstrated AI’s capability to diagnose and grade prostate cancer comparably to expert pathologists. However, external validations on diverse data sets have been limited and often show reduced performance. Historically, there have been no well-established guidelines for AI study designs and validation methods. Diagnostic assessments of AI systems often lack preregistered protocols and rigorous external cohort sampling, essential for reliable evidence of their safety and accuracy.

Methods and analysis
This study protocol covers the retrospective validation of an AI system for prostate biopsy assessment. The primary objective of the study is to develop a high-performing and robust AI model for diagnosis and Gleason scoring of prostate cancer in core needle biopsies, and at scale evaluate whether it can generalise to fully external data from independent patients, pathology laboratories and digitalisation platforms. The secondary objectives cover AI performance in estimating cancer extent and detecting cribriform prostate cancer and perineural invasion. This protocol outlines the steps for data collection, predefined partitioning of data cohorts for AI model training and validation, model development and predetermined statistical analyses, ensuring systematic development and comprehensive validation of the system. The protocol adheres to Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis+AI (TRIPOD+AI), Protocol Items for External Cohort Evaluation of a Deep Learning System in Cancer Diagnostics (PIECES), Checklist for AI in Medical Imaging (CLAIM) and other relevant best practices.

Ethics and dissemination
Data collection and usage were approved by the respective ethical review boards of each participating clinical laboratory, and centralised anonymised data handling was approved by the Swedish Ethical Review Authority. The study will be conducted in agreement with the Helsinki Declaration. The findings will be disseminated in peer-reviewed publications (open access).

Introduction
Most older adults living in residential aged care facilities (RACFs) have at least one marker of potentially suboptimal prescribing. Pharmacists play a crucial role in medication management, with their effectiveness enhanced by using computerised decision support tools. The Pharmacists Review to Optimise Medicines in Residential Aged Care (PROMPT-RC) study aims to optimise medicine use by providing pharmacists in RACFs with an electronic medicine management app with integrated decision support (AusTAPER App/Pathway) to use as part of medication reviews they undertake.

Methods and analysis
The PROMPT-RC study is a parallel cluster randomised controlled trial design involving Australian RACFs. It will assess if pharmacists’ use of the AusTAPER App/Pathway for medication reviews improves medication regimens for RACF residents compared with usual care. Pharmacists in RACFs randomised to the intervention arm will be trained to use the AusTAPER App/Pathway, which flags potentially inappropriate medicines (PIMs) across a person’s entire medicine regimen. Pharmacists in RACFs randomised to the control arm will not have access to the AusTAPER App/Pathway—they will continue to provide usual care. The primary outcome is the difference in the number of regular medicines between treatment arms at 12 months. Secondary outcomes will measure the number of regular and pro re nata medicines, PIMs, medicine administration times, medicine regimen complexity, use of antipsychotics, antidepressants, and benzodiazepines, quality of life, mortality, instances of physical restraint, and the number of falls, hospitalisations and general practitioner/health professional visits. The cost-effectiveness of the AusTAPER App/Pathway compared with usual care will be calculated. Data collection will occur at baseline, 3, 6, 9 and 12 months postrandomisation and 3 and 6 months prebaseline. We aim to recruit 668 participants to adjust for an estimated 10% loss to follow-up, giving 334 participants in each arm. Data analysis will follow an intention-to-treat approach using a linear mixed model.

Ethics and dissemination
Ethical approval was obtained from The University of Western Australia Human Research Ethics Committee (Reference: 2024/ET000525; approved 14 August 2024). Reciprocal approval was also obtained in other states. This study is registered on the Australian New Zealand Clinical Trials Registry (https://anzctr.org.au). Trial findings will be disseminated through national and international peer-reviewed publications and conferences.

Trial registration number
ACTRN12624001409561.

To the Editor On behalf of our coauthors, we write to report an error in an immunoblot for BCL2 for patient 2 in Figure 1B of our article “Association of a MicroRNA/TP53 Feedback Circuitry With Pathogenesis and Outcome of B-Cell Chronic Lymphocytic Leukemia,” published in JAMA on January 5, 2011. Apparently, a careful reader brought concern about this figure panel to the attention of the journal editors, who shared the concern with us. First of all, we would like to thank the reader and the journal editors for bringing this issue to our attention. We take these concerns very seriously and we aim to preserve rigor in science.

No medical diagnosis is more fraught than child physical abuse. Implications are grave for the child, family, and community. If abuse is missed in its earliest stages, children may experience further injury, permanent disability, or death. If not present, an abuse diagnosis risks family disruption, lost trust, and delayed medical diagnoses. Abuse is not a single pathophysiological entity with consistent examination findings, laboratory results, natural history, or imaging. Unlike most pediatric illnesses, caregivers may resist diagnostic efforts, perhaps by providing information that is incomplete or misleading. The diagnosis is often challenged in legal proceedings, occasionally by deploying specious theories of causation with limited scientific support. When available, child abuse pediatricians, who have additional training and experience, can provide subspecialist consultation to address these challenges, but the diagnosis is also often first made by frontline clinicians.

This multicenter randomized clinical trial examines the effect of middle meningeal artery embolization on the recurrence of chronic subdural hematoma in patients who previously underwent an operation and are at high risk of recurrence.

Stroke, Ahead of Print. BACKGROUND:As populations age, there is an increasing need to optimize endovascular treatment (EVT) and to understand country-specific differences in East Asia. We harmonized stroke registries from Korea and Taiwan to enable comparisons of patient characteristics and outcomes, with a particular focus on the impact of age.METHODS:Multicenter prospective stroke registries in Korea (CRCS-K [Clinical Research Collaboration for Stroke in Korea]) and Taiwan (TREAT-AIS [Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke]) were harmonized to form a unified data set of patients undergoing EVT. Outcomes included 3-month modified Rankin Scale, symptomatic intracranial hemorrhage, and successful recanalization. We assessed the association between age and outcomes in the overall population and those who were aged ≥80 years using logistic regression models, adjusting for relevant covariates.RESULTS:A total of 9934 EVT cases (7835 from Korea and 2099 from Taiwan) were included from 2011 to 2023. Patients had a mean age of 70.1±12.9 years (57.6% male; median National Institutes of Health Stroke Scale score, 14 [interquartile range, 9–19]). Compared with Korean patients, Taiwanese patients had a higher prevalence of risk factors and more severe strokes, contributing to lower rates of favorable 3-month outcomes. Increasing age was associated with poorer EVT results; among patients ≥80 years, 18% achieved a modified Rankin Scale score of 0 to 2, compared with 46% of younger patients. However, the risk of symptomatic intracranial hemorrhage did not significantly increase with age (adjusted odds ratio per year, 1.01 [0.99–1.02]; adjusted odds ratio of ≥80 years, 0.98 [0.75–1.29]). Prestroke functional independence, baseline hemoglobin, and bridging thrombolysis were identified as significant modifiers of outcomes in the oldest patients.CONCLUSIONS:Taiwanese EVT patients had more risk factors and worse outcomes than Korean patients. Advanced age is associated with poorer functional recovery, yet selected older patients, particularly those who were functionally independent before the stroke or received bridging thrombolysis, demonstrated meaningful benefit. These results underscore the importance of individualized treatment strategies and careful patient selection, especially as populations continue to age.

Background
Early-onset gastric cancer (EOGC) is a lethal malignancy. It differs from late-onset gastric cancer (LOGC) in clinical and molecular characteristics. The current strategies for EOGC detection have certain limitations in diagnostic performance due to the rising trend in EOGC.

Objective
We developed a liquid biopsy signature for EOGC detection.

Design
We use a systematic discovery approach by analysing genome-wide transcriptomic profiling data from EOGC (n=43), LOGC (n=31) and age-matched non-disease controls (n=37) tissue samples. An extracellular vesicle-derived long non-coding RNA (EV-lncRNA) signature was identified in blood samples from a training cohort (n=299), and subsequently confirmed by qPCR in two external validation cohorts (n=462 and n=438), a preoperative/postoperative cohort (n=66) and a gastrointestinal tumour cohort (n=225).

Results
A three EV-lncRNA (NALT1, PTENP1 and HOTTIP) liquid biopsy signature was developed for EOGC detection with an area under the receiver operating characteristic curve (AUROC) of 0.924 (95% CI 0.889 to 0.953). This EV-lncRNA signature provided robust diagnostic performance in two external validation cohorts (Xi’an cohort: AUROC, 0.911; Beijing cohort: AUROC, 0.9323). Furthermore, the EV-lncRNA signature reliably identified resectable stage EOGC patients (stage I/II) and demonstrated better diagnostic performance than traditional GC-related biomarkers in distinguishing early-stage EOGC (stage I) from precancerous lesions. The low levels of this biomarker in postsurgery and other gastrointestinal tumour plasma samples indicated its GC specificity.

Conclusions
The newly developed EV-lncRNA signature effectively identified EOGC patients at a resectable stage with enhanced precision, thereby improving the prognosis of patients who would have otherwise missed the curative treatment window.

Introduction: the hidden labour behind clinical guidelines The British Society of Gastroenterology’s (BSG) latest 5-year national guideline for inflammatory bowel disease (IBD)1 has recently completed. This adjunct commentary to the guideline contains the reflections of two chairs—one methodological, one clinical—who steered the process. It is not written to seek praise or indulgence but rather to lay bare the pragmatic decisions, structural challenges and emerging questions that surfaced while leading the guideline process. We offer five key insights to inform future BSG guideline work and to contribute to international dialogue on how we produce, update and future-proof clinical guidance in increasingly complex evidence environments. Breadth versus usability: how big is too big? The scope of this guideline is vast—over 100 000 words, 43 recommendations, 114 good practice statements with nearly 800 original manuscripts referenced, prompting peer review to suggest relegating many visual and tabular summaries to supplementary…

This May, the World Health Assembly (WHA) will vote on re-establishing a mandate for the WHO to address the health consequences of nuclear weapons and war.1 Health professionals and their associations should urge their governments to support such a mandate and support the new United Nations (UN) comprehensive study on the effects of nuclear war. The first atomic bomb exploded in the New Mexico desert 80 years ago, in July 1945. Three weeks later, two relatively small (by today’s standards), tactical-size nuclear weapons unleashed a cataclysm of radioactive incineration on Hiroshima and Nagasaki. By the end of 1945, about 213 000 people were dead.2 Tens of thousands more have died from late effects of the bombings. Last December, Nihon Hidankyo, a movement that brings together atomic bomb survivors, was awarded the Nobel Peace Prize for its ‘efforts to achieve a world free of nuclear weapons…

Circulation, Volume 152, Issue 1, Page 58-73, July 8, 2025. The increasing demand for donor hearts presents both a critical challenge and a significant opportunity for innovation in cardiac transplantation. Advancements in immunosuppressive regimens and genetic engineering have reignited recent interest in xenotransplantation. Notably, 2 human patients have received genetically modified pig hearts under expanded-access authorization. They survived for 40 and 60 days, with xenograft failure preceding death in both cases. Concurrently, decedent studies have focused on monitoring the short-term physiological function of genetically modified cardiac xenografts in legally brain-dead recipients, representing a novel experimental paradigm for preclinical testing to help bridge the gap between nonhuman primate studies and clinical trials. These contemporary achievements build on a large body of exploratory efforts in cardiac xenotransplantation in nonhuman primates. Despite significant progress in overcoming hyperacute rejection, adaptive cellular and humoral immunological barriers remain. This review aims to critically evaluate the current advancements in xenotransplantation, to explore ongoing challenges, and to discuss the future potential of this innovative approach in addressing the growing demand for donor organs in cardiac transplantation.

Objectives
COVID-19 in children is generally of short duration, but some may take longer to recover. This study investigated the time to symptom resolution following SARS-CoV-2 infection among children in a community setting on the outskirts of an urban centre in Brazil.

Design
Prospective cohort study.

Setting
This is a community-based cohort of children living in Manguinhos, a favela in Rio de Janeiro. The cohort was followed through home visits and telephone monitoring of symptoms. The analysis focused on symptomatic children from this cohort with confirmed SARS-CoV-2 infection. Recovery time was defined as the interval between the first date with symptoms and the first date without symptoms following a positive SARS-CoV-2 test.

Participants
A total of 1276 children (boys and girls aged 2–

Introduction
Guidelines for symptomatic knee osteoarthritis (OA) dictate the initiation of conservative treatment (physical therapy, analgesics and intra-articular injections with corticosteroids) as a first line defence. When conservative treatment fails, the golden standard is invasive joint replacement surgery, but for a substantial group of patients who do not respond to the current conservative treatment, this is not (yet) indicated. The RADIOPHENOL study investigates if denervation of knee sensory (genicular) nerves can serve the gap between conservative and invasive treatment for younger patients and for patients who cannot undergo joint replacement surgery due to comorbid health conditions.

Methods and analysis
The RADIOPHENOL study is a multicentre unblinded randomised controlled trial with three parallel arms (1:1:1). In total, 192 patients with knee OA Kellgren-Lawrence grades 2–4 but not eligible for joint replacement according to the orthopaedic surgeon due to young age, old age and/or comorbidity or technical reasons are eligible and will be randomised to three groups of 64 patients. Group A: traditional radiofrequency ablation, group B: chemical neurolysis with phenol, group C: conservative medical management. Primary outcome is the Oxford Knee Score at 6 months. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index, knee pain by numeric rating scale, physical functionality, health-related quality of life, mental health, change in medication use, predictive value of a diagnostic block, procedure time, patient discomfort score during the intervention and adverse events.

Ethics and dissemination
The protocol (V.2.0, 15 May 2023), was approved by the Ethics Committee of Amsterdam UMC (NL83410.018.22 – METC2022.0890) on 31 July 2023. We aim to publish our results in international peer-reviewed journals.

Trial registration details
ClinicalTrials.gov NCT06094660, including the WHO Trial Registration data set items. Registered on 20 October 2023, first patient enrolled on 27 November 2023.

Objective
Marked gender differences have been observed in ‘deaths of despair’, with suicides, drug overdoses and alcohol-related diseases more common among men. The present study examines whether men use fewer mental healthcare services than women during the years before dying from diseases of despair.

Design
Retrospective cohort study: population-wide administrative register data, covering all registered inhabitants of Norway, are analysed using descriptive statistics, logistic regression and ordinary least squares linear probability models. The regression models are adjusted for age and sociodemographic covariates (marriage, immigrant background, education and employment status), measured at baseline (2008).

Setting
Norway 2008–2017.

Participants
Men (number of observations (n) = 1 593 044) and women (n=1 569 717) who fell within the 15–69 age range in 2008 and were still alive and residing in Norway in 2014.

Outcome measures
Mental healthcare utilisation during a 6-year period (2009–2014) is monitored in men and women who died prematurely (