Risultati per: Cardio-oncology: rivista open access

Stroke, Ahead of Print.

Introduction
There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.

Methods and analysis
PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.

Ethics and dissemination
Ethical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.

Trial registration number
ISRCTN30448031; EudraCT number: 2021-005748-31.

New England Journal of Medicine, Ahead of Print.

Introduction
The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming standard of care in many parts of the world. While observational studies in the USA and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real-world data for this technique and generalisability of outcome in other economic regions.

Methods and analysis
The arrhythmias with as low as reasonably achievable X-ray exposure study is a prospective, observational, multicentre and multinational open-label registry study. Up to 700 patients undergoing catheter ablation for right-sided supraventricular arrhythmias (according to national guidelines) will be enrolled for the routine use of the EnSite Precision 3D mapping system. Participating sites are distributed in 13 countries from Central Eastern Europe, North and South Africa, the Middle East and the CIS (Commonwealth of Independent States), with different levels of expertise using minimal fluoroscopic exposure techniques. After electrophysiological procedure, patients will be followed up for 6 months either in-clinic or via telephone interview. Patients will be asked to complete a study questionnaire at enrolment and 6 months after the invasive procedure to assess quality of life changes secondary to the procedure. The study’s primary objective is to describe ionising radiation exposure during catheter ablation when the EnSite Precision 3D mapping system is used in supraventricular tachycardia ablation. The study’s secondary objective is to assess the safety and efficacy of this method. Furthermore, fluoroscopy timing, total procedure time, success rate and complications will be reported.

Ethics and dissemination
The study was approved by the ethics committee at Mohammed Bin Khalifa Specialist Cardiac Centre (BDF/R&REC/2020-504) and the medical ethics committees of all participating sites. Participants will be required to provide informed consent before enrolment in the study. The study results will be published and presented at conferences.

Trial registration number
NCT04716270

Objectives
To examine correlates of Neisseria gonorrhoeae antimicrobial resistance (AMR) to first-line antimicrobials (azithromycin, cefixime and ceftriaxone).

Design and setting
The sentinel surveillance network is an open cohort of gonococcal infection cases from Québec, Canada. Cross-sectional results are reported herein.

Participants
Between 1 January 2016 and 31 December 2019, data from 886 individuals accounting for 941 gonorrhoea cases were included.

Methods
Epidemiological and clinical data were collected using an auto-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. Generalised estimating equations were used for regression.

Results
The prevalence of azithromycin resistance with a minimal inhibitory concentration (MIC) of ≥2 mg/L was 21.3%. In 2016, men who have sex with men were more likely to be infected with an azithromycin-resistant N. gonorrhoeae isolate (adjusted prevalence ratio (aPR)=4.73, 95% CI 1.48 to 15.19) or with an isolate with increased third-generation cephalosporin (3GC) MIC (aPR=5.32, 95% CI 1.17 to 24.11 for cefixime (MIC≥0.06 mg/L) and aPR=4.38, 95% CI 1.53 to 12.54 for ceftriaxone (MIC≥0.03 mg/L)). However, these associations were not maintained between 2017 and 2019, with increased MIC observed in men who have sex exclusively with women and women. Overall, azithromycin resistance was significantly more likely in cases who self-reported HIV infection (aPR=1.65, 95% CI 1.00 to 2.71). Cefixime increased MIC were more likely in individuals 25–34 years old (aPR=2.23, 95% CI 1.18 to 4.21). Cefixime and ceftriaxone increased MIC were both more likely in cases who reported ≥5 sexual partners (cefixime: aPR=2.10, 95% CI 1.34 to 3.27 and ceftriaxone: aPR=1.62, 95% CI 1.14 to 2.30).

Conclusion
Significant correlates of N. gonorrhoeae AMR to first-line antimicrobials were observed. Antimicrobial stewardship may be particularly important for 3GC. Active monitoring and interventions are critical for 3GC non-susceptible strains, especially considering the very low prevalence in Québec.

Introduction
BedMed-Frail explores risks and benefits of switching antihypertensives from morning to bedtime in a frail population at greater risk of hypotensive adverse effects.

Methods and analysis
Design: Prospective parallel randomised, open-label, blinded end-point trial.
Participants: Hypertensive continuing care residents, in either long-term care or supportive living, who are free from glaucoma, and using ≥1 once daily antihypertensive.
Setting: 16 volunteer continuing care facilities in Alberta, Canada, with eligible residents identified using electronic health claims data.
Intervention: All non-opted out eligible residents are randomised centrally by the provincial health data steward to bedtime versus usual care (typically morning) administration of once daily antihypertensives. Timing changes are made (maximum one change per week) by usual care facility pharmacists.
Follow-up: Via linked governmental healthcare databases tracking hospital, continuing care and community medical services.
Primary outcome: Composite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke, or congestive heart failure.
Secondary outcomes: Each primary outcome element on its own, all-cause unplanned hospitalisation or emergency department visit, non-vertebral fracture and, as assessed roughly 135 days postrandomisation, fall in the last 30 days, deteriorated cognition, urinary incontinence, decubitus skin ulceration, inappropriate or disruptive behaviour a minimum of 4 days per week, and receipt of antipsychotic medication or physical restraints in the last 7 days.
Process outcome: Proportion of blood pressure medication doses taken at bedtime (broken down monthly).
Primary outcome analysis: Cox-Proportional Hazards Survival Analysis.
Sample size: The trial will continue until a projected 368 primary outcome events have occurred.
Current status: Enrolment is ongoing with 642 randomisations to date (75% female, mean age 88 years).

Ethics and dissemination
BedMed-Frail has ethical approval from the University of Alberta Health Ethics Review Board (Pro00086129) and will publish results in a peer-reviewed journal.

Trial registration number
NCT04054648.

Introduction
Monkeypox was originally endemic locally in West Africa; however, outbreaks in non-endemic countries have been recognised since May 2022. The effectiveness of tecovirimat has been estimated against smallpox, which belongs to the same Orthopoxvirus genus as monkeypox. Thus, tecovirimat is expected to be effective against monkeypox. This study aims to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox and monkeypox and to prepare a scheme for oral tecovirimat use in Japan.

Methods and analysis
This nationwide, multicentre, non-randomised, open-label, double-arm study will involve viral examination of the blood, throat swabs, urine and skin lesions, performed periodically. Participants will freely decide whether to participate in an administered group (supportive treatment plus oral tecovirimat) or a non-administered group (only supportive treatment). Tecovirimat will be administered for 14 days. To ensure that financial problems do not preclude participation in the study, the research fund will cover the cost of tecovirimat and basic hospitalisation fees. The primary endpoint is the percentage of patients with negative PCR results (cycle threshold value ≥40) for skin lesion specimens at 14 days after inclusion in the study. Secondary endpoints include mortality at 14 and 30 days, viral load in each sample, duration of fever and adverse events. The sample size is estimated to be 50 patients with monkeypox or smallpox.

Ethics and dissemination
Written informed consent will be obtained from all participants. This study was approved by the Certified Review Board of National Center for Global Health and Medicine and published in the Japan Registry of Clinical Trials. The results of this study will be published in peer-reviewed journals and/or in presentations at academic conferences.

Trial registration number
jRCTs031220169.

This Viewpoint explains the history of the Comstock Act, its use by those seeking to restrict abortion, and why it threatens abortion access in the US.

This Viewpoint argues that making a progestin-only contraceptive pill available for sale as an over-the-counter product will help reduce logistic barriers to safe and effective birth control.

The Original Investigation titled “Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma: The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial,” published online March 16, 2023, in the May 2023 print issue, has changed license status to open access (CC-BY-NC-ND license). This article has been updated online.

JAMA Oncology is committed to publishing influential original research, opinions, and reviews that advance the science of oncology and improve the clinical care of patients with cancer.

Annals of Internal Medicine, Ahead of Print.

Introduction
Colistin is a lipopeptide antibiotic administered as an inactive prodrug—colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity, dependent on plasma concentrations. The number of patients with infections caused by multidrug-resistant Gram-negative bacteria sensitive only to colistin and the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment.

Methods and analysis
The COL-ECMO2022 study is a prospective, non-randomised, single-centre, phase IV pharmacokinetic clinical trial designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. Up to 30 patients treated with colistin will be included in the study and assigned to one of two arms, depending on the presence/absence of ECMO. All study participants will receive standard CMS dose intravenously. The plasma concentrations of colistin and CMS taken at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals. A population pharmacokinetic model will be developed to assess the influence of ECMO on pharmacokinetics. A difference greater than 25% is considered clinically significant.

Ethics and dissemination
The study has been approved by the Ethics Committee of St. Anne’s University Hospital Brno (Number 10ML/2022-AM). Related manuscripts will be submitted to peer-review journals.

Trial registration numbers
EudraCT Number 2022-000291-19; NCT05542446.

New England Journal of Medicine, Ahead of Print.

Introduction
Patients with cancer undergoing chemotherapy experience various physical and psychological problems and discomfort. Virtual reality (VR) can be used in technology-based non-pharmacological therapy that can serve as a potential distractor in the symptom management of patients with cancer undergoing chemotherapy. We propose a smartphone-based virtual reality relaxation (S-VR) technique as a complementary modality to provide comfort to patients with cancer, and we will evaluate its effect on patients with cancer undergoing chemotherapy.

Methods and analysis
We will recruit 80 patients from the One Day Chemotherapy ‘Tulip’ Center of Dr. Sardjito General Hospital, Yogyakarta, Indonesia. This will be a two-arm parallel randomised controlled trial, with a 1:1 allocation and the primary outcome assessor blinded. This study will be divided into two groups: (1) an intervention group, with participants receiving 360° panoramic video content and music relaxation intervention through a VR device (head-mounted display) placed on their head during chemotherapy for ±10 min plus standard care and (2) a control group, with participants receiving guided imagery relaxation therapy in the form of a leaflet plus standard care. We will measure the outcomes after one chemotherapy cycle for each participant. The primary outcome is the effectiveness of the S-VR in improving the comfort of patients. The secondary outcome is the effect of the S-VR on the patients’ symptom management self-efficacy, pain, anxiety, blood pressure (systolic blood pressure and diastolic blood pressure) and pulse rate.

Ethics and dissemination
This study was approved by the Medical and Health Research Ethics Committee of the Faculty of Medicine, Public Health and Nursing of Universitas Gadjah Mada—Dr. Sardjito General Hospital, Yogyakarta, Institutional Review Board (approval number: KE/FK/0301/EC/2023). Written informed consent will be obtained from all participants who enrol in the study. Dissemination will be conducted through peer-reviewed publications and conference presentations.

Trial registration number
NCT05756465.

This study estimates changes in geographic access and drive times to gender clinics following legislation enacted to restrict puberty-suppressing medications and hormones for those younger than 18 years.