Search Results for: Terapia antibiotica: breve durata vs. lunga durata

This individual participant data meta-analysis compares the association between antipsychotic (vs placebo) acute-phase treatment and outcomes in individuals who were not recently treated to recently treated individuals.

This randomized clinical trial examines the efficacy and safety of zilebesiran vs placebo when added to a standard antihypertensive medication in adult patients with uncontrolled hypertension.

Background
High blood pressure (BP) is a significant global health issue, with many treated patients failing to achieve BP control. The Triple Pill vs Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial evaluated the effectiveness, cost-effectiveness and acceptability of early use of low-dose triple fixed-dose combination of BP-lowering drugs (‘triple pill’) compared with usual care in the management of hypertension. The TRIUMPH trial showed superior BP control with the triple pill strategy compared with usual care. This process evaluation of the TRIUMPH trial aimed to explore the contextual factors that influenced the trial outcomes, implementation of the triple pill strategy, mechanisms of its effects and potential barriers and facilitators for implementing the triple pill strategy in routine practice.

Methods
Guided by the UK Medical Research Council’s framework, semistructured interviews were conducted with 23 patients and 13 healthcare providers involved in the TRIUMPH trial. Data were analysed using the framework analysis method in NVivo.

Results
Hypertension care in Sri Lanka was hindered by the absence of systematic screening and overcrowded public clinics. Despite free medication provision at public clinics, long waiting times and occasional stock-outs posed challenges. In the TRIUMPH trial, both intervention and usual care were delivered in the context of ‘better than usual’ care, including team-based management, reduced waiting times, monetary assistance for travel, routine adherence monitoring and intensive follow-up. The triple pill strategy provided a simplified regimen, better access to BP-lowering medications and better BP-lowering efficacy. Key barriers to implementation in routine practice included the triple pill’s large size, therapeutic inertia and restrictive regulatory policies regarding fixed-dose combinations.

Conclusions
Implementation of the triple pill strategy into routine practice requires health system strengthening, provider training and supportive policy measures to replicate its effectiveness seen in the trial.

Trial registration number
ACTRN12612001120864, SLCTR/2015/020.

Objectives
This systematic review investigated available evidence on the stand-alone and incremental predictive performance of ophthalmic artery Doppler (OAD) for pre-eclampsia.

Design
Systematic review.

Data sources
We conducted a literature search from PubMed (Medline), the Cochrane CENTRAL, EMBASE and Scopus from inception to 8 April 2025.

Eligibility criteria
Studies eligible for inclusion were prospective or retrospective cohort studies, case-control studies or randomised controlled trials that reported on the predictive performance of OAD for pre-eclampsia in singleton pregnancies; and conducted in either high-income country (HIC) or low- and middle-income country (LMIC).

Data extraction and synthesis
Two reviewers independently screened and assessed articles for inclusion. One reviewer then extracted data using a standardised data extraction sheet, and any uncertainties were discussed with a second reviewer. The Prediction model Risk of Bias Assessment Tool was used for quality and risk of bias assessment. Findings were summarised and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and synthesised qualitatively.

Results
We identified and included 11 observational studies (3 from HIC and 8 from LMICs) with a total of 12 150 singleton pregnancies, of which 517 (4.3%) were complicated by pre-eclampsia at end of follow-up. The included studies were of varied quality, with three at low risk of bias, four at unclear risk and four at high risk. No interventional study was identified. Three studies (27.3%) recruited high-risk pregnancies (defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as one or more of the following: chronic hypertension, personal or family history of pre-eclampsia, early (≤18 years) or late (≥40 years) first pregnancy, primipaternity, chronic kidney disease, increased body mass index >30 kg/m2, presence of diabetes mellitus prior to pregnancy, autoimmune disease and thrombophilia), while eight studies (72.7%) recruited undetermined risk pregnancies. Stand-alone performance of OAD (interpreted by area under the receiver operating curve at 95% CI) showed that in the first trimester, the peak systolic velocity (PSV) ratio demonstrated very good predictive ability (0.97, 95% CI 0.92 to 1.0) (n=1 study), and the second PSV (PSV2) demonstrated very good predictive ability (0.91, 95% CI 0.82 to 0.99) (n=1 study). Also, PSV2 demonstrated fair predictive ability (0.61, 95% CI 0.42 to 0.79; and 0.53, 95% CI 0.40 to 0.66) for early and late pre-eclampsia, respectively (n=1 study). In the second trimester, the PSV ratio demonstrated very good predictive ability (0.88, 95% CI 0.84 to 0.91) (n=1 study), and PSV2 demonstrated good predictive ability (0.73, 95% CI 0.66 to 0.81; and 0.76, 95% CI 0.71 to 0.81) for pre-eclampsia (n=2 studies). In the third trimester, the PSV ratio demonstrated good predictive ability (0.82, 95% CI 0.73 to 0.89; and 0.77, 95% CI 0.71 to 0.82) for preterm and term pre-eclampsia, respectively (n=1 study). Also, PSV2 demonstrated good predictive ability 0.70 (0.57 to 0.84) (n=1 study).
Subsequently, in the second trimester, PSV ratio demonstrated better incremental predictive performance than uterine artery pulsatility index for preterm pre-eclampsia, when added to maternal factors and mean arterial pressure (MAP) (56.1%–80.2% vs 56.1%–74.8% detection rate (DR) at 10% FPR) (n=1 study). Also in the third trimester, adding PSV ratio to maternal factors and MAP was superior to soluble fms-like tyrosine kinase-1/placental growth factor ratio in predicting pre-eclampsia at

Introduction
Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prophylaxis in non-valvular atrial fibrillation. Yet, DOAC use is regarded as a contraindication for intravenous thrombolysis in acute ischaemic stroke. The stratification of patients into ‘on-therapy’ and ‘off-therapy’ categories based on their plasma DOAC concentrations is particularly crucial in the acute phase of stroke when decisions for thrombolysis or anticoagulation reversal are time-sensitive. The novel point-of-care DOAC dipstick assay (DOASENSE) rapidly assesses urine for clinically significant DOAC levels, potentially broadening eligibility for thrombolysis or targeted reversal therapy. This multicentre prospective observational registry study aims to evaluate the accuracy and clinical utility of DOAC dipstick testing compared with plasma DOAC assays in acute stroke management across regional Australian hospitals.

Methods and analysis
This multicentre, prospective, observational study will enrol participants presenting to hospitals across Victoria and Tasmania with acute ischaemic stroke or intracerebral haemorrhage with DOAC ingestion within 48 hours of presentation. Plasma DOAC concentrations measured by chromogenic assays will be compared with rapid urine dipstick results from DOASENSE testing. There is a target sample size of 146 participants. The primary outcomes are as follows: (1) proportion of ischaemic stroke participants with off-therapy plasma DOAC levels and (2) eligibility for reperfusion therapy based on DOASENSE and plasma DOAC concentrations. Secondary outcomes are follows: (1) ischaemic stroke aetiology for participants with on-therapy vs off-therapy DOAC levels; (2) proportion of participants meeting criteria for pharmacological DOAC reversal based on DOASENSE outcomes; (3) incidence of false-negative and false positive DOASENSE results in clinically significant DOAC plasma concentrations at a threshold of ≥30 ng/mL and (4) an exploratory analysis of any false negative DOASENSE assays to identify potential contributing factors.

Ethics and dissemination
Ethics approval has been granted by the Eastern Health Human Research Ethics Committee (reference number: 99628). Dissemination of findings will occur through peer-reviewed publications and academic conferences.

Studio dell’Istituto nazionale tumori su terapia non chirurgica

Studio dell’Istituto nazionale tumori su terapia non chirurgica

Objectives
Childhood vitamin D deficiency is a public health issue. This study aims to systematically evaluate vitamin D nutritional status among children and adolescents in Mainland China through a quantitative analysis of literature, providing evidence-based strategies for prevention.

Design
This is a systematic review and meta-analysis, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
A comprehensive search strategy was implemented across eight electronic databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang and CBM) from inception to February 2024.

Eligibility criteria
We included cross-sectional studies that measured serum 25-hydroxyvitamin D levels and analysed influencing factors (eg, age, season, region) in healthy children and adolescents aged 0–18 years in Mainland China; studies reporting prevalence data of vitamin D deficiency/insufficiency based on standardised thresholds (deficiency

Importance
Background rates are critical for contextualising safety signals arising from COVID-19-related interventions in investigational or real-world settings.

Objective
To estimate background rates of medical events of interest (MEI) for which COVID-19 infection and/or COVID-19 interventions may be risk factors in two US claims databases.

Design, setting and participants
This retrospective cohort study spans the pre-COVID-19 (2018–2019) and COVID-19 (2020–2021) periods. We constructed three cohorts, in each of Inovalon/HealthVerity (Inovalon/HV) and Optum databases: a COVID-19-positive adult cohort (2020–2021), a paediatric cohort (2018–2021) and a high-risk cohort (2018–2021) comprising patients at increased risk for severe COVID-19. Participants were indexed on the day they first qualified to enter each cohort during the study period. Background rates of 17 MEI were estimated per 1000 person-years (PY) with 95% CIs.

Main outcomes and measures
Annual incidence rates (IRs) of 17 MEI.

Results
Overall, 758 414 (COVID-19-positive adults; 57.8% women), 12 513 664 (high-risk adults; 56.8% women) and 8 510 627 (paediatric patients; 49.1% women) patients were identified in the HV database. IRs of MEI varied substantially by year, data source, study cohort and duration of follow-up. The IRs of MEI were highest among COVID-19-positive adults and lowest among paediatric patients. For example, IR of myocarditis/pericarditis per 1000 PY was 3.0 (95% CI: 2.6 to 3.4) in the COVID-19-positive adult cohort vs 0.36 (95% CI: 0.34 to 0.37) among high-risk adults and 0.05 (95% CI: 0.05 to 0.06) among paediatric patients. In the COVID-19-positive adult cohort, we observed higher IRs during 90-day follow-up (eg, IR of acute myocardial infarction (AMI) 26.5 (95% CI: 25.3 to 27.7)) vs 365-day follow-up (eg, IR of AMI 20.0 (95% CI: 9.2 to 20.8)) and during 2020 compared with 2021. IRs were higher in the high-risk adult and paediatric populations during the pre-COVID-19 period than during the COVID-19 pandemic.

Conclusions
Substantial variability was observed in IRs of MEI by study cohort, year, data source and follow-up duration. When generating background rates for contextualising safety signals from COVID-19 interventions, careful consideration must be given to the indicated subpopulation of interest, COVID-19-related temporal variations and data sources.

A base di cellule pancreatiche derivate da staminali, studio 1/2

Objectives
The New York City (NYC) HIV Care Coordination Programme (CCP) is designed to help people with HIV (PWH) overcome barriers to care and treatment engagement. We assessed preferences for CCP components among programme enrollees (’clients’) and providers. Our objective is to compare client and provider preferences, which were previously analysed separately.

Design
We used a discrete choice experiment to assess preferences for four CCP features (‘attributes’): Help with Adherence to Antiretroviral Therapy (ART), Help with Primary Care Appointments, Help with Issues other than Primary Care and Where Programme Visits Happen. Each of these attributes had 3–4 variants (‘levels’). In the original surveys, levels within Where Programme Visits Happen varied by participant type (client vs provider). We recoded the levels by visit location (VL) or by travel time (TT) to make them comparable and report results from both approaches.

Setting
25 Ryan White Part A-funded NYC CCPs participated.

Participants
152 providers and 181 clients completed the survey.

Primary and secondary outcome measures
Preferences were quantified using the relative importance of the attributes and utility of the levels.

Results
From January 2020 to March 2021, 152 providers and 181 clients completed the survey. Most of the providers (52%) were

Per pazienti di nuova diagnosi non idonei alla chemioterapia

Objective
Amoxicillin-clavulanate is commonly used to prevent infections following snakebites despite the lack of clinical evidence. We aimed to demonstrate that clinically directed initiation of amoxicillin-clavulanate would be non-inferior to routine use in this setting.

Design
Open-label, randomised, non-inferiority trial with blinded adjudication of endpoints.

Setting
Emergency department of a teaching hospital in southern India.

Participants
Adults with local swelling following snakebites within 24 hours of bite.

Interventions
In the routine use strategy, intravenous followed by oral amoxicillin-clavulanate was administered for at least 5 days. In the clinically directed strategy, the antibiotic was only initiated for clinical failures.

Primary and secondary outcome measures
Primary outcomes were protocol-defined clinical failure and total antibiotic consumption. Non-inferiority margin was prespecified as 10%. Secondary outcomes were the length of hospital stay, total antivenom consumption, new-onset organ failure, bleeding requiring transfusion, death/need for surgical intervention and drug-related adverse events.

Results
The trial was prematurely stopped due to the COVID-19 situation after randomising 66 patients—34 to clinically directed initiation and 32 to routine use arms. Russell’s viper was the most common (21 (32%)) biting snake species identified; 52 (79%) patients had evidence of haemotoxic envenomation at baseline, and 24 (36%) patients developed AKI. There were 10 clinical failures—six in the clinically directed initiation arm and four in the routine use arm. The difference in clinical failure between the two arms was 5.2% (–12.0%–21.7%; p=0.291); the upper bound of the CI exceeded the prespecified non-inferiority margin. Total antibiotic consumption, expressed in DDDs, was significantly lower in the clinically directed initiation arm (0 (0–1) vs 5.31 (4.67–6.17); p

Potrebbe sembrare fantascienza, ma è medicina sperimentale con basi molto concrete: 10 persone affette da diabete di tipo 1 non hanno più bisogno di iniettarsi insulina da oltre un anno,…

Circulation, Ahead of Print. BACKGROUND:Combining antiplatelet therapy (APT) with conventional anticoagulants increases the risk of bleeding. In the AZALEA-TIMI 71 trial (Safety and Tolerability of Abelacimab [MAA868] vs Rivaroxaban in Patients With Atrial Fibrillation), the novel factor XI inhibitor abelacimab significantly reduced the risk of bleeding compared with rivaroxaban in patients with atrial fibrillation. Whether the safety of combination antithrombotic therapy differs in the context of factor XI inhibition has not been well characterized.METHODS:This prespecified analysis of AZALEA-TIMI 71 includes patients randomized between March and December of 2021 to 1 of 2 subcutaneous monthly abelacimab doses (90 or 150 mg) or oral rivaroxaban (20 mg daily, dose reduced to 15 mg in patients with creatinine clearance ≤50 mL/min), stratified by planned use of concomitant APT. The primary composite of major or clinically relevant nonmajor bleeding and other safety and efficacy outcomes were examined by concomitant APT and randomized treatment.RESULTS:Of 1287 patients (44% female; median age, 74 years [interquartile range, 69–78]), 318 (24.7%) were on APT at baseline with planned continuation (15.5% aspirin only, 7.5% P2Y12inhibitor only, and 1.6% dual APT). In the rivaroxaban arm, the rate of major or clinically relevant nonmajor bleeding was 10.6% per 100 patient-years with concomitant APT versus 7.7% per 100 patient-years without. In the abelacimab arms, the rates were 2.5% and 3.5% per 100 patient-years for the 90-mg and 150-mg doses, respectively, with concomitant APT and 2.7% and 3.1% per 100 patient-years without. Each abelacimab dose significantly reduced major or clinically relevant nonmajor bleeding compared with rivaroxaban, both in those with concomitant APT (adjusted hazard ratio, 0.26 [95% CI, 0.10–0.70] and hazard ratio, 0.30 [95% CI, 0.12–0.74] for 90 mg and 150 mg of abelacimab, respectively, versus rivaroxaban) and in those without concomitant APT (adjusted hazard ratio, 0.34 [95% CI, 0.19–0.60] and hazard ratio, 0.40 [95% CI, 0.23–0.68] for 90 mg and 150 mg of abelacimab, respectively;Pinteractions=0.56 and 0.60, respectively). Patients with concomitant APT tended to derive greater absolute risk reductions with abelacimab (8.1% and 7.1% for 90 mg and 150 mg of abelacimab, respectively, versus rivaroxaban) than those without concomitant APT (5.0% and 4.6%, respectively).CONCLUSIONS:Inhibition of factor XI with abelacimab consistently reduced bleeding compared with rivaroxaban regardless of concomitant APT use, with greater absolute reductions in bleeding in those requiring concomitant APT. These data suggest that factor XI inhibition may be a safe anticoagulant option in patients with atrial fibrillation requiring concomitant APT.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT04755283.

Study objectives
The longitudinal associations of sleep timing and time in bed (TIB) with all-cause, cardiovascular and non-cardiovascular mortality are unclear in Chinese rural populations.

Methods
This population-based cohort study included 2468 participants who were aged ≥60 years and residing in rural communities in western Shandong Province. Sleep timing and TIB were assessed using standard questionnaires at baseline in 2014. Mid-sleep time was defined as the halfway point between the bedtime and wake-up time. Vital status until December 2022 and causes of death for all participants were ascertained via death registry plus interviews with informants (eg, family members or village doctors). Data were analysed using restricted cubic splines (RCS) and Cox proportional-hazards models.

Results
During the mean follow-up of 7.36 (SD 2.03) years, 657 participants died. The RCS analysis showed non-linear relationships of sleep duration and mid-sleep time at baseline with all-cause and cardiovascular mortality. Specifically, when baseline sleep characteristics were categorised into tertiles, the multivariable-adjusted HR for all-cause mortality was higher for long sleep duration ( >8 vs 7–8 hours; HR 1.27; 95% CI 1.06 to 1.53), long TIB ( >9 vs