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This systematic review and meta-analysis compares depression rating outcomes with ketamine vs electroconvulsive therapy in adults with major depressive episode and compares response and remission rates, number of sessions to response and remission, and adverse effects.
This randomized clinical trial investigates whether first-line treatment with nivolumab plus ipilimumab vs nivolumab alone improves objective response rate in adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
This cross-sectional study of data from the Surveillance, Epidemiology and End Results database assesses temporal trends in the use of active surveillance and watchful waiting vs definitive treatment in men with low- and favorable intermediate–risk prostate cancer in the US between 2010 and 2018.
Neonatologi, ‘necessità in aumento, garantirla in tutta Italia’
Neonatologi, ‘necessità in aumento, garantirla in tutta Italia’
To the Editor The recent CAPLA multicenter trial reported that patients had no improvement in arrhythmia-free survival after single ablation in persistent atrial fibrillation (AF) with posterior wall isolation (PWI) in addition to pulmonary vein isolation (PVI) vs PVI alone. This finding contradicts outcome data from multiple randomized trials, which have demonstrated incremental benefit of PWI. We are concerned that there appear to have been some major weaknesses in the study design and the ablation strategy, which may have affected the results of this study.
In Reply The CAPLA study was the first and largest (N = 338) randomized multicenter international study to compare PVI alone with PVI with PWI using radiofrequency ablation in patients with persistent AF. First, we agree with the goal expressed by Dr Mohanty and colleagues to improve outcomes with ablation in patients with persistent AF, and we share their disappointment with the lack of improvement in arrhythmia outcomes with the addition of PWI. However, the findings from CAPLA were consistent with those from similarly rigorous multicenter randomized trials with intensive follow-up, which have not reported a benefit of any add-on strategy to PVI in patients with persistent AF. In fact, contrary to the assertion by Mohanty and colleagues, a meta-analysis that included 17 studies (14 observational, 3 randomized) in patients with paroxysmal and persistent AF did not confirm an incremental benefit with PWI. Indeed, a small randomized study of 110 patients with persistent AF using the cryoballoon showed no significant reduction in all atrial arrhythmias with addition of PWI to PVI alone.
Circulation, Ahead of Print. Background:Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As pre-specified secondary endpoints, the TRANSFORM-HF trial compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF.Methods:TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2,859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomized in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on pre-specified secondary endpoints, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (PHQ-2) (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months.Results:Baseline data were available for 2,787 (97.5%) patients for KCCQ-CSS and 2,624 (91.8%) patients for PHQ-2. Median baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12-months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference 0.06 [95% CI, -2.26 to 2.37];P=0.96) or the proportion of patients with PHQ-2 score ≥3 (15.1% vs 13.2%:P=0.34). Results for KCCQ-CSS were similar at 1-month (adjusted mean difference 1.36 [95% CI, -0.64 to 3.36];P=0.18) and 6-month follow-up (adjusted mean difference -0.37 [95% CI, -2.52 to 1.78];P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent prior to hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization.Conclusions:Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, prior loop diuretic use, and baseline health status.
In Reply The TRANSFORM-HF investigators thank Dr Wolowich for his comments on our trial. We appreciate his perspectives related to CYP sequence variants and a potential impact on torsemide metabolism. These metabolism issues were not overlooked in the trial, but rather were antithetical to the question of loop diuretic strategy that we designed the trial to assess. Specifically, we evaluated these therapies head to head regardless of a multitude of patient and clinician considerations, including dosing conversion ratio and dosing frequency as well as factors such as intraparticipant or interparticipant variation in response. Genetic testing for CYP sequence variants is not routinely performed in clinical practice, whether for diuretics or other common cardiovascular medications. For instance, even for medications such as clopidogrel, which has well-documented differences in CYP metabolism, these evaluations are not standard of care. Furthermore, heart failure guidelines do not recommend routine assessment of genetic variants for medication management aside from specific cardiomyopathies (eg, cardiac amyloid). Moreover, the mechanistic and outcome studies that informed our hypothesis for TRANSFORM-HF did not incorporate such testing. Therefore, genetic testing in the context of a pragmatic trial would have challenged the fundamental study design, execution, and generalizability.
In Reply In response to the insightful questions by Drs Ashraf and Ashraf, we agree that understanding participants’ prior exposure to infection is generally informative to understanding treatment response in the setting of an infectious disease. Unfortunately, quantifying exposure and infection during the COVID-19 pandemic has been a considerable challenge.
This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.
To the Editor JAMA recently published the TRANSFORM-HF study, which reported that torsemide was no better than furosemide in preventing death due to heart failure in patients with chronic heart failure. The authors urged caution in interpretation of the null result and listed a number of issues with the study, including loss to follow-up, participant crossover, and dosing adherence. However, I believe they overlooked an important aspect of torsemide that could have been responsible for failure to demonstrate a benefit in TRANSFORM-HF.
To the Editor COVID-19 and its treatment have been of great interest to psychiatrists due to its neurological and psychiatric effects. Therefore, we read with great interest the recent randomized clinical trial report and Editorial that examined the effect of fluvoxamine on time to recovery in outpatients with mild to moderate COVID-19. We would like to comment on some concerns we have about this study.
Introduction
The chronic inflammatory state in rheumatoid arthritis (RA) augments the risk of cardiovascular disease (CVD), with pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin 6 (IL-6) playing a vital role. Consequently, biological disease-modifying antirheumatic drugs (bDMARDs) may attenuate that risk. IL-6 is also a myokine, secreted from exercising skeletal muscles, where IL-6 exhibits anti-inflammatory effects that may ameliorate the risk of CVD. In healthy humans treated with IL-6 signalling inhibitors (IL-6i), exercise induced loss of visceral fat mass and cardiac adaptations were abolished. We hypothesise that IL-6 signalling inhibition will impair the cardiac and metabolic adaptions to exercise training compared with TNF inhibition in RA patients.
Methods and analysis
80 RA patients treated with IL-6i (n=40) or TNF inhibitors (n=40) are included in a 12-week randomised investigator-blinded 4×4 min high-intensity interval training (HIIT) study. Patients are stratified for medical treatment and sex and allocated 1:1 to an exercise or a no exercise control group (four groups). The supervised exercise intervention comprises 3 weekly HIIT sessions on an ergometer bicycle. The primary outcome is the change in left ventricular mass (LVM), and key secondary outcome is change in visceral fat mass. Both outcomes are measured by MRI. Primary statistical analysis will evaluate LVM at follow-up in a regression model. Intention-to-treat and per protocol analyses will be conducted. The latter necessitates a minimum attendance rate of 80%, adherence to bDMARDs treatment of ≥80% and minimum 8 min (50%) of maximal heart rate above 85% per session.
Ethics and dissemination
The study has been approved by the Capital Region Ethics Committee (H-21010559 amendments 86424, 87463 and 88044) and the Danish Medicines Agency (2021-b005287-21). The trial will follow ICH-GCP guidelines. Regardless of outcome, results will be published in relevant peer-reviewed journals.
Trial registration numbers
Eudra-CT: 2021-b005287-21 and NCT05215509.
Può ridurre gli effetti collaterali rispetto alla radioterapia
In Reply The Letter by Dr Hsu and colleagues provides further insight into the reasons why children who were randomized to high-flow nasal oxygen therapy had a longer length of hospital stay than children treated with standard oxygen therapy in our study. We agree with the Letter authors’ comments, except that our study protocol provided no additional observation period after cessation of high-flow oxygen therapy, so this factor could not have substantially contributed to the results. We support the notion that there are excessive ICU admissions for infants with bronchiolitis. The PARIS-2 trial excluded infants with bronchiolitis because they were studied in the PARIS-1 trial.
