Risultati per: Cardio-oncology: rivista open access

Background
Globally, there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID-19). Repurposing existing medications may offer the best hope for treating patients with COVID-19 to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents. The IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC) trial is a randomised controlled trial that will investigate whether time to clinical improvement in patients with COVID-19 is improved following a 14-day course of IMU-838+oseltamivir versus oseltamivir alone.

Methods
IONIC trial is an open-label study in which participants will be randomised 1:1 in two parallel arms: the intervention arm (IMU-838+oseltamivir) and the control arm (oseltamivir only). The primary outcome is time to clinical improvement; defined as the time from randomisation to a two-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and funded by LifeArc.

Discussion
The IONIC protocol describes an overarching trial design to provide reliable evidence on the effectiveness of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (oseltamivir) (IONIC intervention) for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.

Ethics and dissemination
This study has been independently reviewed and approved by Wales Research Ethics Committee. In addition, required regulatory approvals were received from Medicines and Healthcare products Regulatory Agency.

Trial registration number
EudraCT 2020-001805-21, ISRCTN53038326, NCT04516915.

Objective
To investigate and explore the barriers of access and utilisation of sexual and reproductive health (SRH) services among adolescents.

Design
An explanatory sequential mixed-methods design was implemented with two phases. The questionnaire was created and used by five trained research assistants for the quantitative component of the study (phase I). In phase II, the qualitative component of the study included focus group discussions (FGDs) with adolescents.

Setting
This study was conducted in rural areas of five secondary schools in Arsi zone, Ethiopia.

Participants
In both phases, 15–19 years adolescents participated in the study. For the quantitative phase, a total of 800 randomly selected adolescents responded to the questionnaire, while 24 adolescents participated during FGDs until data saturation was reached.

Primary and secondary outcome measures
For outcome variables, the respondents were asked if they used any SRH services in the past 12 months. It was recorded as 0=no and 1=yes.

Results
Overall, SRH service utilisation was 208 (26.1%) among adolescents. Being aged 17–19 years (adjusted OR, AOR 3.44, 95% CI 2.15 to 5.51). Grades 11 and 12 (AOR 2.70, 95% CI 1.22 to 2.32). Lack of income (AOR 0.0.43, 95% CI 0.31 to 0.61). Ever had sexual contact (AOR 3.04 CI 95% CI 2.15 to 4.29) and being knowledgeable on SRH service (AOR 1.47, 95% CI 1.05 to 2.05) were factors associated with outcome variable. The barriers hindering access and use of SRH services were found at the facility level, provider level, community level and personal level.

Conclusion
The research found a low level of SRH services access and utilisation among adolescents due to several factors. Interventions to design-specific policies and educational programmes are needed to promote healthy practices.

Restrictions and supply disruptions brought on by the COVID-19 pandemic reduced access to sexual and reproductive health (SRH) services around the world, according to a review published in BMJ Global Health. These services include contraception, abortion, gender-based and intimate partner violence follow-up, and sexually transmitted infection (STI) treatment and prevention.

Introduction
This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment.

Methods and analysis
This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48.

Ethics and dissemination
The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public.

Trial registration number
jRCTs071200011.

New England Journal of Medicine, Ahead of Print.

Introduction
Donor-derived modified immune cells (MIC) induced long-term specific immunosuppression against the allogeneic donor in preclinical models of transplantation. In a phase I clinical trial (TOL-1 Study), MIC treatment resulted in a cellular phenotype that was directly and indirectly suppressive to the recipient’s immune system allowing for reduction of conventional immunosuppressive therapy. Here, we describe a protocol for a randomised controlled, multicentre phase-IIb clinical trial of individualised immunosuppression with intravenously administered donor MIC compared with standard-of-care (SoC) in living donor kidney transplantation (TOL-2 Study).

Methods and analysis
Sixty-three living donor kidney transplant recipients from six German transplant centres are randomised 2:1 to treatment with MIC (MIC group, N=42) or no treatment with MIC (control arm, N=21). MIC are manufactured from donor peripheral blood mononuclear cells under Good Manufacturing Practice conditions. The primary objective of this trial is to determine the efficacy of MIC treatment together with reduced conventional immunosuppressive therapy in terms of achieving an operational tolerance-like phenotype compared with SoC 12 months after MIC administration. Key secondary endpoints are the number of patient-relevant infections as well as a composite of biopsy-proven acute rejection, graft loss, graft dysfunction or death. Immunosuppressive therapy of MIC-treated patients is reduced during follow-up under an extended immunological monitoring including human leucocyte antigen-antibody testing, and determination of lymphocyte subsets, for example, regulatory B lymphocytes (Breg) and antidonor T cell response. A Data Safety Monitoring Board has been established to allow an independent assessment of safety and efficacy.

Ethics and dissemination
Ethical approval has been provided by the Ethics Committee of the Medical Faculty of the University of Heidelberg, Heidelberg, Germany (AFmu-580/2021, 17 March 2022) and from the Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institute, Langen, Germany (Vorlage-Nr. 4586/02, 21 March 2022). Written informed consent will be obtained from all patients and respective donors prior to enrolment in the study. The results from the TOL-2 Study will be published in peer-reviewed medical journals and will be presented at symposia and scientific meetings.

Trial registration number
NCT05365672.

Il periodico scientifico, diretto da Antonio Gasbarrini, punta a proporsi come punto di riferimento per il settore della nutrizione e della biodiversità

Introduction
Cotreatment of HIV and tuberculosis (TB) reduces morbidity and mortality in coinfected patients. Availability of antiretroviral treatment (ART) drug options, including within drug classes, is important, particularly in high HIV/TB burden low and middle-income countries.

Methods and analysis
This is a phase 2b, open-label, non-comparative randomised controlled trial to assess the antiretroviral activity of a fixed-drug, single tablet, combination of bictegravir (BIC) 50 mg/emtricitabine (FTC) 200 mg/tenofovir alafenamide (TAF) 25 mg (Biktarvy). The primary objective is to determine the efficacy, safety and pharmacokinetics of two times per day, coformulated BIC 50 mg/FTC 200 mg/TAF 25 mg in HIV-positive ART-naïve patients with TB who are receiving a rifampicin-based treatment regimen and to characterise viral suppression rates at week 24 through to week 48 in the BIC/FTC/TAF arm. We will enrol 120 patients randomised in a 2:1 ratio to the intervention or control arm of the study. A non-comparative contemporaneous control arm in which participants receive a dolutegravir-based regimen (standard of care) will also be enrolled.

Ethics and dissemination
The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and the South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval (trial reference numbers: BREC/00001300/2020 and SAHPRA 20200810). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.

Trial registration number
Clinicaltrials.gov; Trial registration number: NCT04734652; South African National Clinical Trials Register (SANCTR DOH-27-012021-6789)

Introduction
Skin cancer is a common disease in the tropics, and oncological resection typically requires reconstruction with skin grafts. Fibrin glue, initially established as a haemostatic agent, has been studied extensively as an adhesive for skin grafts in burns. This study aims to investigate the use of fibrin as an adhesive for split skin grafts in skin cancers.

Methods and analysis
The study design is a prospective randomised controlled trial with the aim of investigating the impact of two different methods of split skin graft fixation. The intervention of fibrin glue will be compared with the control of staples or sutures. The trial will be conducted at two sites, a public hospital and a private hospital in Townsville, Australia, over a 24-month period with 334 participants to be recruited. Consecutive patients presenting for skin excisions and grafting will be eligible to participate in this study. Randomisation will be on the level of the patient. The primary outcome is graft take based on wound healing at 1 month. Secondary outcomes will be pain on dressing changes and operative time.

Ethics and dissemination
The study has been approved by The Townsville University Hospital Human Research Ethics Committee. Findings will be disseminated in conference presentations and journals and through online electronic media.

Trial registration number
ACTRN12618000484246.

Introduction
Breast reconstruction plays an important role for many in restoring form and function of the breast after mastectomy. However, rates of breast reconstruction in the USA vary significantly by race, ethnicity and socioeconomic status. The lower rates of breast reconstruction in non-white women and in women of lower socioeconomic status may reflect a complex interplay between patient and physician factors and access to care. It remains unknown what community-specific barriers may be impacting receipt of breast reconstruction.

Methods and analysis
This is a mixed-methods study combining qualitative patient interview data with quantitative practice patterns to develop an actionable plan to address disparities in breast reconstruction in the local community. The primary aims are to (1) capture barriers to breast reconstruction for patients in the local community, (2) quantitatively evaluate practice patterns at the host institution and (3) identify issues and prioritise interventions for change using community-based engagement.

Ethics and dissemination
Ethics approval was obtained at the investigators’ institution. Results from both the quantitative and qualitative portions of the study will be circulated via peer-review publication. These findings will also serve as pilot data for extramural funding to implement and evaluate these proposed solutions.

Circulation, Ahead of Print. Background:Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care following percutaneous coronary intervention (PCI). However, some adverse non-cardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retain the antithrombotic efficacy, but its combination with a P2Y12 inhibitor is still lack of randomized clinical trial (RCT) evidence.Methods:In this randomized, open-label, non-inferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent (DES) implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75mg/d for 12 months) or conventional DAPT (aspirin 100mg/d plus clopidogrel 75mg/d for 12 months). The primary endpoint was a 1-year composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), ischemic stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) criteria type 2, 3 or 5 bleeding. The endpoints were adjudicated by an independent Clinical Event Committee.Results:Between January 11, 2018 and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary endpoint occurred in 101 (4.47%) patients in the indobufen-based DAPT group and 140 (6.11%) patients in the conventional DAPT group (absolute difference -1.63%, pnon-inferiority 0.05). The occurrence of BARC criteria type 2, 3 or 5 bleeding events was lower in the indobufen-based DAPT group compared to the conventional DAPT group (2.97% vs 4.71%, HR 0.63, 95%CI 0.46 to 0.85, p=0.002), with main decrease in type 2 bleeding (1.68% vs 3.49%, HR 0.48, 95%CI 0.33 to 0.70, p

Evidence-based care for early pregnancy is well established and includes strong evidence for safe abortion as part of the reproductive health care spectrum. Legal interference to provision of safe, accessible abortion diverts the time, attention, and skills of clinicians from other pressing health concerns, especially improving maternal health and birth equity. The rate of maternal mortality in the US, already unacceptably high, surged from 20.1 deaths per 100 000 live births in 2019 to 23.8 deaths per 100 000 live births in 2020; the increases were significantly higher for Black and Hispanic people. Maternal deaths (during pregnancy or within 42 days of the end of pregnancy from any cause related to or aggravated by the pregnancy or its management) are anticipated to increase as evolving abortion restriction laws undermine physicians’ ethical and professional mandate to prioritize patients’ well-being.

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.

The FDA issued new guidance designed to make naloxone more readily available for reversing opioid overdoses in underserved areas.

The Original Investigation “Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post–COVID-19 Conditions,” published online September 7, 2022, was changed to open access status under a CC-BY license. This article was corrected online.

This randomized clinical trial compares the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer.