Search Results for: Le cause della polmonite nei bambini

Introduction
Liver cirrhosis and its severe complication, oesophageal variceal bleeding (EVB), pose significant health risks. Standard treatment for EVB combines non-selective beta-blockers (NSBB) with endoscopic variceal ligation (EVL). Carvedilol, an NSBB with additional benefits, is preferred for compensated cirrhosis. However, no randomised controlled trial (RCT) has compared carvedilol with propranolol, a conventional NSBB, in combination with EVL for secondary prophylaxis. This study aims to compare the effectiveness and safety of these treatments in preventing variceal rebleeding or death in patients with cirrhosis and EVB.

Methods and analysis
This multicentre, RCT is scheduled to begin in December 2024, with recruitment and follow-up continuing until December 2026. Eligible participants are patients with liver cirrhosis and EVB. Participants are randomly assigned in a 1:1 ratio to receive EVL combined with either carvedilol or propranolol. The primary endpoint is the incidence of variceal rebleeding or all-cause death. Secondary endpoints include all-cause death, liver-related death, each of the complications of portal hypertension (overt ascites, overt hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis), hepatocellular carcinoma, changes in liver function (assessed by Child-Pugh and Model for End-Stage Liver Disease scores), changes in liver stiffness, changes in spleen stiffness, and adverse events. Subgroup and sensitivity analyses will be conducted to evaluate the consistency and robustness of the treatment effects. A total sample size of 524 patients (262 per group) is required to detect a significant difference between the treatment arms.

Ethics and dissemination
The study protocol has been approved by the ethics committee of the First Hospital of China Medical University (No. 2024-656-2). The study will follow the Declaration of Helsinki and Good Clinical Practice guidelines. The findings of this trial will be disseminated through peer-reviewed publications, conference presentations and healthcare professionals to guide future clinical practice.

Trial registration number
Chinese Clinical Trial Registry (Registration number: ChiCTR2400089692).

Circulation, Ahead of Print. Background: Intramural site of origin is a major cause of ablation failure of ventricular arrhythmias and the optimal strategy is unclear. This study investigated the efficacy of a stepwise ablation approach for intramural outflow tract (OT) premature ventricular complexes (PVCs) guided by mapping of the septal coronary venous system.Methods: Consecutive patients with OT PVCs were included in which an intramural origin was confirmed by demonstration of earliest activation in a septal coronary vein. Radiofrequency ablation was performed from the closest endocardial site in the left (LVOT) and/or right ventricular OT (RVOT) independent of the local activation time. If there was no suppression by endocardial ablation, retrograde transvenous ethanol infusion with a single or double balloon technique was performed, targeting the earliest septal coronary vein. If venous anatomy was not suitable for ethanol ablation or if this failed, bipolar ablation was performed.Results: Sixty patients (age 61±12 years, 78% male) were included. The mean QRS duration of the PVC was 150.8±17.6 ms with a maximum deflection index of 0.51±0.11, and the most common ECG pattern was a left bundle branch block with inferior axis and V3 transition (63%) followed by a right bundle branch block with inferior axis and no transition (27%). Earliest ventricular activation (28.6±11.2 ms pre-QRS) was recorded in the left ventricular annular vein in 15 cases and a septal perforator vein in 45 cases. Acute PVC suppression at the end of the procedure was achieved in all cases. In 87% of cases (n=52), endocardial ablation from the endocardial LVOT, RVOT or both was successful in eliminating the PVC. In the remaining 8 patients, the PVC was eliminated with ethanol infusion (n=7) and bipolar ablation (n=1). Complications included one case of pericardial effusion related to venous mapping. During follow-up (17±24 months), the PVC burden was reduced from 28±12% to 2.3±4.7% and long-term success (≥80% burden reduction) was 88%.Conclusions: Most intramural OT PVCs can be successfully eliminated with endocardial ablation adjacent to the earliest intramural activation site. A high success rate is achieved when following a stepwise approach, with bailout ablation strategies required in a minority of cases.

Introduction
Out-of-hospital cardiac arrest is a public health concern with a high mortality rate. Hypoxic ischaemic brain injury is the primary cause of death in patients admitted to the intensive care unit (ICU) after return of spontaneous circulation (ROSC). Several systemic factors, such as hypotension, can exacerbate brain injuries. International guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg. Several observational studies suggest that a higher MAP may be associated with better outcomes, but no randomised trials have shown an effect of higher MAP. The ongoing METAPHORE (mean arterial pressure after out-of-hospital cardiac arrest) trial aims to compare a standard MAP threshold (MAP ≥65 mm Hg) with a high MAP threshold (MAP ≥90 mm Hg) to evaluate whether implementing a higher MAP threshold can improve neurological outcomes in patients admitted to ICU after cardiac arrest.

Methods and analysis
METAPHORE is a randomised, controlled, multicentre, open-label trial with a blinded primary outcome assessor, comparing two parallel groups of patients 18 years of age or older, receiving invasive mechanical ventilation for coma defined by a Glasgow Coma Score ≤8/15 after out-of-hospital cardiac arrest and sustained ROSC. Eligible patients are randomly assigned in a 1:1 ratio to either a MAP target threshold of 65 mm Hg or higher throughout the ICU stay (control group) or a MAP target threshold of 90 mm Hg or higher during the first 24 hours after randomisation, followed by 65 mm Hg or higher for the remainder of the ICU stay (intervention group). Both groups receive the same general care concerning post-cardiac arrest syndrome management according to international guidelines. The primary endpoint is the proportion of patients with a favourable neurological outcome as defined by a modified Rankin scale (mRS) of 0 to 3 measured on day 180 after inclusion by a psychologist blinded to the allocation of the intervention. Secondary outcomes are the proportion of patients alive at ICU and hospital discharge, at day 28 and day 180; proportion of patients alive at ICU discharge with a mRS of 0 to 3; the EuroQOL-5D-5L at day 180; the Clinical Frailty Scale at day 180; the number of ICU-free days, ventilator-free days, catecholamine-free days and renal replacement therapy-free days at day 28; the proportion of patients with acute kidney injury stage 3 and need for renal replacement therapy within ICU stay and proportion of patients with persistent need for renal replacement therapy at ICU discharge; and safety outcomes (cardiovascular, neurological, cutaneous, digestive and haemorrhagic complications within 7 days after inclusion). Subgroup analyses are planned according to initial cardiac arrest rhythm (shockable or non-shockable), chronic hypertension and Cardiac Arrest Hospital Prognosis score. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in October 2024 in 27 French ICUs, and a sample of 1380 patients is expected by October 2027.

Ethics and dissemination
The study received approval from the national ethics review board on 8 February 2024 (Comité de Protection des Personnes Sud-Est V – 2023-A00257-38). Patients are included after informed consent has been obtained either from a proxy or through an emergency procedure. Results will be submitted for publication in peer-reviewed journals.

Trial registration number
ClinicalTrials.gov: NCT05486884.

Stroke, Ahead of Print. BACKGROUND:Diagnosing cerebral amyloid angiopathy (CAA) after spontaneous lobar intracerebral hemorrhage has significant clinical implications. A previous postmortem study found that the presence of both subarachnoid hemorrhage (SAH) and hematoma finger-like projections (FLP) on acute-stage computed tomography strongly rules in CAA. In the present study, we assessed the diagnostic value of these imaging markers against histopathologic diagnosis in less severe presentations.METHODS:This retrospective (2002–2022) multicenter study included patients aged ≥45 years with lobar intracerebral hemorrhage of unknown cause, for whom acute-stage computed tomography or magnetic resonance imaging and neuropathological samples from hematoma evacuation or biopsy were available. Centralized consensus reading (2 raters) of imaging and neuropathological data (including Aβ immunohistochemistry) were performed. Analysis was restricted to samples containing at least 10 vessels. The diagnostic performance was evaluated against the neuropathological reference, that is, CAA/no CAA.RESULTS:We analyzed data from 66 patients (age, 65±9 years; men, 33%; hematoma volume, 45±26 mL; death within 1 year, 14%) from 6 French centers. Neuropathological material included samples from hematoma evacuation (n=48) and biopsy (n=18). CAA was present in 38 patients (58%), and FLP and SAH were observed in 29 (44%) and 50 (76%) patients, respectively. FLP had a sensitivity of 0.58 (95% CI, 0.41–0.74) and a specificity of 0.74 (95% CI, 0.54–0.89) for the diagnosis of CAA. SAH demonstrated a high sensitivity of 0.92 (95% CI, 0.78–0.98; negative predictive value=0.80 [0.52–0.96]) but moderate specificity of 0.43 (95% CI, 0.24–0.63). The combined presence of FLP and SAH had a specificity of 0.54 (95% CI, 0.37–0.71) and a sensitivity of 0.79 (95% CI, 0.59–0.92).CONCLUSIONS:This study is the first to evaluate the diagnostic performance of FLP and SAH with histopathologic reference in nonautopsied patients. The results suggest these markers have lower diagnostic performance than previously reported in severe hematomas leading to early death. However, the high sensitivity of SAH suggests its potential clinical utility in ruling out CAA when absent.

Stroke, Ahead of Print. BACKGROUND:Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear.METHODS:This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024. The study included 4552 adults (2005 female; median age, 73 years) with ischemic stroke and no seizure history. Seizures were classified using International League Against Epilepsy definitions. We examined ASyS occurring within seven days after stroke. The main outcomes were all-cause mortality and epilepsy. Validation of the updated SeLECT score (SeLECT-ASyS) was performed in 3 independent cohorts (Switzerland, Argentina, and Japan) collected between 2012 and 2024, including 74 adults with ASyS.RESULTS:The 10-year risk of poststroke epilepsy ranged from 41% to 94%, and mortality from 36% to 100%, depending on ASyS type and timing. ASyS on stroke onset day had a higher epilepsy risk (adjusted hazard ratio [aHR], 2.3 [95% CI, 1.3–4.0];P=0.003) compared with later ASyS. Status epilepticus had the highest epilepsy risk (aHR, 9.6 [95% CI, 3.5–26.7];P

Objective
To characterise patients with metabolic dysfunction-associated steatohepatitis (MASH) in England and to estimate its associated healthcare resource use (HCRU) and costs, both overall and by progression status and comorbidities.

Design
This was a retrospective observational study of adults with a MASH-coded primary and/or secondary care recorded diagnosis in England (2011–2020). The analysis used data from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and death registrations. Annualised all-cause and MASH-related (ie, coded as MASH, end-stage liver disease or major adverse cardiovascular event) HCRU and costs were calculated for patients with incident MASH. Subgroup analyses were conducted for patients with type 2 diabetes, overweight/obesity, cardiovascular disease or progression to cirrhosis. Comparative cost analysis was conducted between those with progressed MASH and those who did not progress.

Results
A total of 2696 patients were included (mean follow-up: 4 years). Incidence of MASH was estimated at 4.7 per 100 000 person-years overall and increased among patients with key comorbidities. Patients who had type 2 diabetes had greater HCRU and costs than those who did not (eg, mean 1.8 vs 1.0 all-cause inpatient admissions and £2227 vs £1151 all-cause inpatient costs per-patient per-year). Some patients with MASH progressed to compensated (8.6%) or decompensated cirrhosis (6.5%) during the study. HCRU and costs were substantially higher among patients who progressed than among those who did not (eg, mean 2.4 vs 1.1 all-cause inpatient admissions and £3620 vs £1290 all-cause inpatient costs per-patient per-year).

Conclusion
HCRU and costs associated with MASH are higher among patients who have cardiometabolic comorbidities or who progress to advanced disease stages. Therefore, efforts to detect cases early and prevent disease progression could reduce healthcare burden.

Stroke, Ahead of Print. BACKGROUND:Stroke is a leading cause of long-term disability, but advances for rehabilitation have lagged those for acute treatment. Large biological studies (eg, omics) may offer mechanistic insights for recovery but require collecting detailed recovery phenotypes at scale, for example, in thousands of people with minimal burden for participants and researchers. This study investigates the concurrent validity between remotely collected wearable sensor data and in-clinic assessments of motor recovery poststroke.METHODS:Utilizing a large, harmonized multisite dataset of adults at various stages of recovery poststroke, we analyzed cross-sectional (N=198; from 0 to >52 weeks) and longitudinal (N=98; from 0 to 26 weeks) changes in the use ratio, the Action Research Arm Test, and the Fugl-Meyer Assessment upper extremity subscale. The use ratio is the ratio of the time the paretic arm is active divided by the time the nonparetic arm is active.RESULTS:Our findings indicate strong concurrent validity of the use ratio, the Action Research Arm Test, and the Fugl-Meyer Assessment upper extremity subscale both cross-sectionally (differences between people) and longitudinally (changes within a person), for example,r=0.87 (95% CI, 0.80–0.91) at 0 to 6 weeks, declining tor=0.58 (95% CI, 0.39–0.72) at ≥52 weeks for correlations between use ratio and Action Research Arm Test.CONCLUSIONS:Although the use ratio strongly correlated with the Fugl-Meyer Assessment upper extremity subscale and Action Research Arm Test early after stroke, these correlations reduced with longer elapsed time poststroke. This decreasing correlation might be explained by the increasing influence that personal and environmental factors play as recovery progresses.

Background
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, with conventional treatments often limited by radiation resistance, systemic toxicity and poor outcomes in advanced stages. Iodine-125 (I-125) seed implantation, combined with chemotherapy and immunotherapy, has emerged as a promising therapeutic strategy, but its efficacy and safety compared with conventional external beam radiotherapy combined with systemic therapies remain unclear. This systematic review and meta-analysis aims to synthesise the available evidence to evaluate the comparative benefits and risks of these treatment modalities.

Methods and analysis
Two reviewers will independently search seven databases—PubMed, Embase, Web of Science and the Cochrane Library—for randomised controlled trials (RCTs). These RCTs should compare the efficacy and safety of I-125 seed implantations combined with chemotherapy and immunotherapy against chemoradiotherapy combined with immunotherapy in patients with NSCLC. The risk of bias in the included studies will be evaluated using the Revised Cochrane risk-of-bias tool V.2. Data synthesis will be conducted using RevMan software. Trial sequential analysis will be applied to the primary outcomes. Additionally, subgroup and sensitivity analyses will be performed to assess the robustness of the findings.

Ethics and dissemination
Ethical approval is not required because this study is a secondary analysis of existing data. We will disseminate the findings through peer-reviewed publications.

PROSPERO registration number
CRD42024591684.

Introduction
A quarter of women experience heavy periods in their lifetime, often significantly impairing their well-being, productivity and quality of life.
Several treatment options are offered for heavy menstrual bleeding; however, there is limited evidence on the effectiveness, safety and cost of available treatments. We aim to conduct a comprehensive systematic review, network meta-analyses and health economic evaluation to compare all available treatment options while considering the views and treatment preferences of women with heavy menstrual bleeding.

Methods and analysis
We will systematically search electronic databases (MEDLINE, EMBASE, CENTRAL) as well as the grey literature, conference proceedings and trial registries to identify all relevant randomised trials that evaluated any medical or surgical treatment for women with heavy menstrual bleeding regardless of their cause compared with placebo or other active treatments.
We will perform pairwise and network meta-analyses using standard methods. We will report primarily on changes in menstrual blood loss (using Pictorial blood loss assessment chart scores or the Alkaline-Haematin method), quality-of-life measures, safety in addition to other important clinical outcomes.
We will develop a health economic model to evaluate the cost-effectiveness of available treatments within a healthcare perspective using data inputs from the planned meta-analyses. We will calculate the incremental cost per change in alternative outcomes and present the net monetary benefit for a range of cost-effectiveness thresholds for quality-adjusted life-year gained. We will conduct consultations and a discrete choice experiment involving patient representatives to capture the factors influencing women’s decision-making and treatment preferences in real life.

Ethics and dissemination
The project was approved by the UCL Institute for Women’s Health Low-Risk Research Ethics Committee (reference: 004_2023_24) and UCL Research Ethics Committee (ID 16351/003) for the planned patient involvement and qualitative research. We will produce an evidence-based decision aid toolkit and will publish the findings in peer-reviewed journals, as well as lay media outputs to inform health professionals, policymakers and the patient community.

PROSPERO registration numbers
https://doi.org/10.17605/OSF.IO/4MUSF, CRD42023468055, CRD42024519622, CRD42024520558 and CRD42024520634.

Chronic back pain is the leading cause of disability worldwide, affecting 1 in 5 adults aged 20 to 59 years. But an analysis of randomized trials and observational studies led a panel of experts to strongly advise against the spine interventions commonly used for chronic axial and radicular back pain in a new clinical guideline. The panel found that the treatments offered little or no relief compared with placebos.

Circulation, Ahead of Print. BACKGROUND:High-volume physical activity (PA) is associated with a higher prevalence of subclinical coronary artery disease (CAD). However, the clinical significance of subclinical CAD among high-volume exercisers remains incompletely understood, and the dose–response relationship between high-volume PA and clinical CAD events remains uncertain.METHODS:Individual participant data from the Cooper Center Longitudinal Study (1987–2018) were linked to Medicare claims files. PA volume was determined by self-report and categorized as

Objectives
Uncertainty exists as to what extent common risk factors are involved in the associations of unemployment with major health outcomes and mortality.

Design
A retrospective and prospective observational study.

Setting
A large population-based French cohort (CONSTANCES).

Participants
99 430 adults at baseline who have been exposed to unemployment during their lifetime and 54 679 of them who were followed for 7 years after baseline.

Primary outcome measures
Testing the mediating roles of several risk factors at baseline in the associations of lifetime unemployment exposure with cardiovascular disease, cancer and mortality rates during a 7-year follow-up. Direct and indirect effects were calculated for each risk factor and all together using logistic regression models adjusted for major confounders including sex, age, parental histories of cardiovascular disease and cancer, social position and working conditions.

Results
Estimates (95% CIs) of the direct and indirect effects for smoking are 0.0083 (0.0044 to 0.0122), p

Herpesviruses and SARS-CoV-2 can disrupt brain cell function and cause neuroinflammation.

Introduction
Guideline-directed medical therapy (GDMT) for heart failure (HF) reduces adverse events, but is underused. Global barriers to GDMT optimisation include low frequency of visits, clinician inertia and poor patient knowledge, which may be mitigated by digital health interventions (DHI). In Brazil, low digital literacy and reduced access to technology may compromise these potential DHI’s beneficial effects. Our objective is to develop and test the effectiveness of a DHI to optimise GDMT in patients recently hospitalised for HF in the Brazilian public health system (Sistema Único de Saúde (SUS)).

Methods and analysis
This is a randomised, controlled, multicentre, parallel-group, clinical trial in which 154 patients being discharged from an HF-related hospitalisation will be randomised. Inclusion criteria are ≥18 years of age, reduced ejection fraction HF (EF

Introduction
The current diagnostic pathway for patients with a suspected inherited bleeding disorder is long, costly, resource intensive, emotionally draining for patients and often futile, as half of patients will remain without a diagnosis and be labelled ‘bleeding disorder of unknown cause’. Advances in understanding the genetic basis of the inherited bleeding disorders, coupled with both increasing infrastructure for genetic/genomic testing and decreasing costs, have increased the feasibility of introducing genomic testing into the clinical diagnostic pathway as a potential solution to improve the care of these patients. Yet, there remain evidence gaps on the optimal integration of genomic analysis into the diagnostic pathway.

Methods and analysis
Using a multicentre randomised-controlled trial design, we will evaluate an early genomic testing strategy for the diagnosis of newly referred patients with a suspected inherited bleeding disorder. Eligible participants will be randomised to early genomic testing diagnostic pathway (intervention) or standard diagnostic pathway (control) and will be followed for a 12-month period. Patients in the control group who remain undiagnosed at study end will be offered identical early genomic testing to ensure equitable access to the intervention. The study will follow a parallel fixed design with waitlist control group and a 1:1 allocation ratio. The study will be conducted at three tertiary care centres in Ontario, Canada, with a target sample size of 212 participants. Clinical utility will be evaluated via the primary outcome of diagnostic yield, as well as the secondary outcome of time to diagnosis. Additional secondary outcomes will allow for assessment of patient impact via health-related quality of life and patient burden measures, as well as evaluation of economic impact through a cost-effectiveness analysis and budget impact analysis.

Ethics and dissemination
This investigator-initiated study was approved by the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board through Clinical Trials Ontario (CTO-4909). Participant informed consent/assent is required. Findings will be disseminated through academic publications.

Trial registration number
ClinicalTrials.gov, NCT06736158.

Introduction
Around 70% of people with psychosis experience auditory verbal hallucinations (AVHs), which can cause distress and impair the social functioning of the individual. AVATAR therapy works by facilitating a ‘face-to-face’ dialogue between the person and a digital representation (avatar) of their persecutory voice. Although there is cumulative evidence of this way of working with voices, enhancing the therapeutic focus on improved confidence and sense of control of the voices in social situations represents a promising way to boost generalisation of therapy gains into social contexts. We aim to enhance AVATAR therapy by incorporating immersive Virtual Reality (VR) social environments aiming to help the person to deal better with their voices in daily situations.

Methods and analysis
A randomised controlled feasibility trial will be conducted. 40 patients aged 18 or above who are at early stages of psychosis (first episode of psychosis in the last five years) and report distressing and interfering voices will be recruited. Participants will be randomised to receive either a novel, enhanced version of AVATAR therapy (AVATAR_VRSocial) in addition to usual care or usual care alone. Assessor-blinded assessments will be conducted at baseline, 3 months (post-intervention) and 6 months (follow­-up). Key therapeutic targets of AVATAR_VRSocial will be those established by the previous evidence of this approach (ie, power and control, self-esteem and future focus), while introducing exposure and management of distressing voices during social interactions. Analyses will focus on feasibility outcomes (recruitment, retention and completion rates) and preliminary estimates of intervention effects. Qualitative interviews will be carried out with participants allocated to AVATAR_VRSocial to gain a comprehensive understanding of participants’ views on the acceptability of the intervention and research procedures. Thematic analysis of the qualitative interviews will assess the acceptability of the intervention, trial procedures and the new VR technology and software involved.

Ethics and dissemination
The study has received ethical approval from the Ethics Commission at the Faculty of Psychology (Ruhr-Universität Bochum), and there is an independent Trial Steering Committee and Lived Experience Advisory Panel also supporting it. Findings will be disseminated through peer­-reviewed publications, conference presentations and science dissemination events.

Trial registration number
ISRCTN35980117.