Risultati per: Cardio-oncology: rivista open access

Introduction
Raltegravir is a potent HIV-integrase strand transfer inhibitor (INSTI). Despite its strong activity against HIV-1 strains resistant to other antiretroviral drug classes, it is usually used in combination with other antiretroviral drugs due to the empirical requirement for anti-HIV drug combinations to ensure effective anti-retroviral therapy (ART). As an early-arriving INSTI, raltegravir is clinically familiar for its safety, tolerability and treatment effectiveness. High-dose calcium carbonate formulated as an antacid (as opposed to a supplement formulation) taken orally together with raltegravir is known to reduce systemic raltegravir exposure due to chelation and reduced absorption. This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral calcium supplementation, on the steady-state pharmacokinetics (PKs) of once-daily oral raltegravir.

Methods and analysis
This is an open-label, three-treatment series in three periods in a single group, fixed-sequence PK study in 12 healthy adult volunteers with HIV on ART. Subjects will take 1200 mg of raltegravir single QD oral dose alone for 7 days (period one), then raltegravir 1200 mg with calcium carbonate 500 mg from day 8 to day 14 (period two) and raltegravir 1200 mg with calcium carbonate 1000 mg from day 15 to day 22 (period three). We will conduct serial PK sampling from observed dosing on days 7, 14 and 21, with 24-hour PK sampling scheduled for days 8, 15 and 22. Follow-up will continue until day 51.

Ethics and dissemination
This study will adhere to the ICH GCP Guidelines and the Declaration of Helsinki. Ethics approval was obtained from the Ottawa Health Science Network Research Ethics Board under study ID 20190750–01 hour. Informed consent will be obtained from all participants prior to enrolment. This protocol will be published in a peer-reviewed journal prior to the study’s completion and closure. Results generated from this activity will also be reported in a peer-reviewed journal.

Trial registration number
NCT04258475.

Introduction
Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.

Methods and analysis
This phase I, open-label, randomised, exploratory, crossover, single-centre prospective controlled trial will employ pharmacokinetic–pharmacodynamic (PK–PD) modelling to assess the variability in bioavailability of nebulised fentanyl administered via intranasal route versus facial aerosol. 20 healthy volunteers will receive three repeated administrations of fentanyl over two visits. At each visit, blood samples (n=11) will be collected for fentanyl quantification by liquid chromatography–tandem mass spectrometry, and pupillary unrest in ambient light (PUAL) measurements (n=9) will be recorded. The resulting data will be analysed using Monolix 2024R1 to model PK–PD relationships, perform Monte Carlo simulations and determine the optimal dosing and timing required to achieve a reduction of more than 30% in PUAL, while also evaluating safety, comfort and tolerance.

Ethics and dissemination
The study has been approved by the Ethic Committee Île-de-France VII (approval reference number: 000216, February 2024) and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed publications, conference presentations and appropriate data-sharing platforms to support further research and clinical application.

Trial registration number
This trial is registered at ClinicalTrials.gov (Identifier: NCT06281951).

New England Journal of Medicine, Volume 393, Issue 1, Page 82-84, July 3, 2025.

Introduction
Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.

Methods and analysis
This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.

Ethics and dissemination
This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.

Trial registration number
jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov).

Objective
Understanding how patients access and experience long-term care after stroke, including the kind of medical support desired, in a qualitative interview study; analysis with a question-focused approach adapted from grounded theory methodology.

Setting
Recruitment in primary care and physical therapy practices in the metropolitan area of Berlin, Germany.

Participants
15 patients treated in general practice or physical therapy, whose last stroke occurred more than 2 years ago.

Results
‘Shaping relationships’ was the core category extracted from the data as a necessary component to receive appropriate long-term care after stroke. Care is embedded in relationships that must be managed primarily by the study participants and their proxies in the German setting. Study participants used different strategies to shape care relationships. This process is helped or hindered by healthcare institutions. Compared with concepts of patient-centred care, patients play a more active role in shaping relationships. To improve long-term care for chronic diseases, this needs to be taken into account.

Conclusion
Shaping relationships is a composite skill that includes engaging in and sustaining relationships, finding and using information and communication. This skill is essential for adequate long-term care after stroke.

Introduction
Breast cancer survival rates in low-income and middle-income countries significantly differ from those in high-income countries, indicating limited access to first-line systemic therapy for advanced and metastatic tumours. Recent studies have demonstrated the benefits of combining cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) with endocrine therapy in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer. However, in Brazil, the population faces limited access to these drugs, particularly in the public healthcare system.

Methods and analysis
This prospective observational study will enrol 300 female patients from 20 cancer centres across Brazil, divided into two groups based on healthcare coverage: those treated in the public healthcare system (group 1) and those treated in the private healthcare system (group 2). The use or non-use of CDK 4/6 inhibitors is not dictated by the study protocol but rather reflects real-world treatment decisions made by attending physicians. Patients will be followed for 24 months, stratified according to CDK 4/6 inhibitor usage. The project aims to assess health inequities by evaluating the prognosis of patients treated in the public versus private healthcare systems. Outcomes include progression-free survival (PFS), overall survival (OS), quality of life and cost-effectiveness. Kaplan-Meier curves will be used to analyse PFS and OS, while the Cox proportional hazards frailty model will be employed to compare outcomes between healthcare systems, adjusting for prognostic variables.

Ethics and dissemination
The study protocol was approved by the Ethics Committee of the HCor Research Institute (Hospital do Coracão/Associacão Beneficente Síria), which served as the central ethics board for the trial (study number: CAAE 42538621.5.1001.0060; approval letter number: 4.571.507; date: 3 March 2021). All participating centres also obtained approval from their respective local ethics committees prior to patient enrolment: Ethics Committee of Hospital de Câncer de Barretos—Fundacão Pio XII; Ethics Committee of Universidade Estadual de Campinas—UNICAMP; Ethics Committee of Faculdade de Minas Muriaé—FAMINAS; Ethics Committee of Hospital Santa Paula—SP; Ethics Committee of Hospital Alemão Oswaldo Cruz—SP; Ethics Committee of Hospital Regional do Câncer de Presidente Prudente—HRCPP; Ethics Committee of Instituto Brasileiro de Controle do Câncer—IBCC/Oncologia Clínica—SP; Ethics Committee of Instituto de Medicina Integral Prof. Fernando Figueira—IMIP/PE; Ethics Committee of Hospital São Rafael; Ethics Committee of Universidade Federal de São Paulo—UNIFESP; Ethics Committee of Hospital Geral de Fortaleza—HGF; Ethics Committee of Casa de Saúde Santa Marcelina; Ethics Committee of Centro Universitário FMABC; Ethics Committee of Liga Norte Riograndense Contra o Câncer; Ethics Committee of Hospital Mãe de Deus/Associacão Educadora São Carlos—AESC; and Ethics Committee of Instituto do Câncer Brasil—ICB. All patients will provide written informed consent. Study findings will be disseminated through scientific publications and presented to a broad range of stakeholders, including patients, physicians, the general public and policymakers.

Trial registration number
ClinicalTrials.gov identifier: NCT05559528—BRaziLian outcomE for metAStatic breasT cancer (BREAST).

Importance
Access to healthy and affordable foods may play a role in reducing inflammation and in healthy pulmonary immune system development.

Objective
To investigate the association between residing in a low-income and low-food-access (LILA) neighbourhood and risk of childhood asthma. A positive association was hypothesised.

Design, setting and participants
This prospective cohort study consists of 16 012 children from 35 longitudinal studies in the Environmental influences on Child Health Outcomes programme (children born 1998–2021) from across the contiguous USA. We conducted survival analyses adjusted for child sex, race/ethnicity, maternal education, gestational smoking, and parental history of asthma.

Exposure(s)
Several commonly used geospatial food access metrics were linked to residential locations including: LILA census tracts where the nearest supermarket is >1 mile in urban and >10 miles in rural areas (LILA1 and 10), >1 mile in urban and >20 miles in rural areas (LILA1 and 20), >0.5 mile in urban and >10 miles in rural areas (LILA0.5 and 10), and >0.5 mile without a vehicle or >20 miles (LILAvehicle). Each metric was linked to lifetime residential history timelines then dichotomised according to whether the child had spent at least 75% of their life living in a LILA area separately for birth through age 5 years (cumulative early childhood) and birth through age 11 years (cumulative middle childhood).

Main outcomes(s) and measure(s)
Asthma incidence in cumulative early and middle childhood.

Results
Residing in a LILA0.5 and 10 and LILAvehicleneighbourhood was associated with a higher asthma incidence in cumulative early and middle childhood. The LILA0.5 and 10 and LILAvehicle associations were stronger for asthma during cumulative early childhood, where we observed hazard ratios of 1.13 (95% CI 1.02 to 1.24) and 1.13 (95% CI 1.01 to 1.27), respectively. The associations were higher among children who were Hispanic, were female and had lower maternal education.

Conclusion and relevance
Limited residential food access was associated with higher childhood asthma incidence, especially among female and Hispanic children and those with lower maternal education. Our findings support multipronged efforts to increase access to healthy and affordable food options and lower food insecurity in LILA neighbourhoods.

Introduction
In the UK National Health Service (NHS), most people with cancer are cared for at oncology outpatient services, where there are no standardised procedures for managing pain. As a result, patients with cancer may receive inadequate care for pain. The Cancer Pain-assessment Toolkit for Use in RoutinE oncology outpatient services aims to assess the feasibility of conducting a multicentre cluster-randomised trial of a systematic pain assessment and management programme integrated within routine care at UK NHS oncology outpatient services. This protocol describes an embedded process evaluation that aims to evaluate the acceptability, fidelity and implementation of the intervention and trial procedures.

Methods and analysis
A combination of methods will be used in the process evaluation. Quantitative data on fidelity and intervention implementation will be collected using case report forms completed at sites, capturing details on training, intervention delivery and adherence. Qualitative data on acceptability and trial experience will be collected through semistructured interviews with intervention recipients (participants), intervention deliverers (healthcare professionals), research nurses and intervention champions. Researcher fieldnotes will also document trial acceptability throughout the trial. Quantitative data will be summarised descriptively. Qualitative data will be analysed using thematic analysis, guided by the framework of acceptability.

Ethics and dissemination
The trial received ethical approval from South Yorkshire Research Ethics Committee and Health Research Authority (21/HRA/5245). Site-specific approvals were obtained from the research and innovation offices at Leeds Teaching Hospital and Hull Teaching Hospital. Trial findings will be disseminated through peer-reviewed publications and via participating sites.

Trial registration number
ISRCTN86926298.

Introduction
Drug-related problems (DRPs) associated with oral anticancer drugs are frequent and require a new healthcare organisation to manage them on an outpatient basis. The aim of this article is to present the study protocol of the Drug Related problems in Oncology Practice (DROP) randomised controlled trial (RCT), endorsed by the French Society for Oncology Pharmacy. The main objective of the DROP RCT is to measure the impact at 6 months of the DROP community/hospital pharmaceutical intervention programme, compared with usual treatment, on the mean number of DRP (ie, adverse effects, drug–drug interactions, medication errors) related to oral anticancer drugs in at-risk outpatients.

Methods and analysis
The DROP protocol is a prospective, multicentre controlled clinical trial, with individual randomisation, comparing in parallel and in open, two groups of outpatients treated with oral anticancer drugs. The interventional group benefits from the DROP multidisciplinary intervention on oral anticancer treatment. The control group receives usual care. The primary outcome of the DROP RCT is the number of DRP due to oral anticancer drugs, per patient, identified between the inclusion of the patient and 6 months after inclusion

Ethics and dissemination
Approval to conduct this study was obtained for all participating centres from an Ethics Committee (Comité de Protection des Personnes Sud-Méditerranée V) in August 2018 in accordance with French law. The trial results will be disseminated at clinical conferences and published in peer-reviewed journals.

Trial registration number
ClinicalTrials.gov: NCT03257969, recruitment started in June 2019. The current protocol version is V.9, 13 December 2023.

Introduction
Neoadjuvant (chemo)radiotherapy (n(C)RT) followed by resection with total mesorectal excision (TME) constitutes the standard treatment for patients with locally advanced rectal cancer of the middle and lower third. However, n(C)RT has demonstrated no significant impact on overall survival but is associated with adverse effects, including impaired sphincter and sexual function. We hypothesise that omitting n(C)RT in selected patients with a clear circumferential resection margin (CRM) >1 mm as determined through preoperative MRI is not inferior regarding local recurrence rate within 3 years after surgery. That treatment approach may show fewer adverse effects and be more cost-effective.

Methods and analysis
Selective neoadjuvant therapy of rectal cancer patients (SELREC) is a randomised controlled, parallel-group, open, multicentre, non-inferiority trial. The experimental intervention involves performing TME surgery without n(C)RT. In contrast, the control intervention adheres to German S3-guidelines, incorporating neoadjuvant radiotherapy (nRT) with a dosage of 5×5 Gy or a total of 50.4 Gy. Additionally, if applicable, concomitant chemotherapy (CT) based on 5-fluorouracil is administered, followed by TME surgery within less than 12 weeks. Adjuvant treatment according to guidelines is allowed depending on the (y)pTNM stage.
The inclusion criteria for this study encompass adult patients with primary adenocarcinoma of the rectum in whom the main tumour mass is located less than 12 cm away from the anal verge, as assessed via proctoscopy. Additionally, eligible participants are required to have a preoperative tumour stage determined by MRI of either T1 or T2 with lymph node involvement (N1) or T3 with no lymph node involvement (N0) or with lymph node involvement (N1) and no distant metastases (M0). The assessment of a clear CRM >1 mm, based on MRI, is another prerequisite for inclusion. A total of 1074 patients in approximately 35 centres are planned to be allocated to the trial.
The primary endpoint of the trial is local recurrence within 3 years after surgery. The primary estimand is based on the full analysis set using a logistic mixed model (margin 3%). The first secondary endpoint is no/minor low anterior resection syndrome (LARS) score at 2 years after surgery, and further secondary endpoints include survival outcomes and quality of life. Safety analysis involves describing the frequencies of major intervention-specific complications, such as the acute toxicity of n(C)RT according to CTCAE and perioperative morbidity and mortality according to Clavien-Dindo criteria.
SELREC is financially supported by the German Federal Ministry of Education and Research.

Ethics and dissemination
This trial has been prospectively registered in the German Clinical Trials Register.
Previously, the study had been approved by the responsible ethics committee of Heidelberg and the local ethics committees of the collaborating institutions before patient enrolment. Any protocol deviation that has an impact on relevant parameters such as study design, endpoints or patient safety will be reported to the responsible ethics committees.
The results will be published in a peer-reviewed scientific journal and on institutional websites.

Trial registration number
German Clinical Trials Register DRKS00030567.

Introduction
African, Caribbean and Black (ACB) communities experience disparities in health outcomes, with higher rates of chronic diseases, such as heart disease and stroke, and lower self-reported health status compared to their White counterparts. Barriers to timely access to healthcare services further exacerbate these inequities. Some studies link racialisation to surgical disparities and subpar surgical outcomes. However, the findings are diverse, and there is no synthesis of the evidence on disparities in surgical care for ACB patients in high-income countries with universal healthcare systems. The objective of the scoping review is to systematically describe, characterise and map the existing literature on disparities in the access to and quality of surgical care among ACB patients in high-income countries with universal healthcare systems, and to identify gaps in the literature on surgical access and quality of surgical care in ACB patients.

Methods and analysis
The scoping review will follow the Joanna Briggs Institute methodology and report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The search strategy will be customised for each database (MEDLINE, Embase, CINAHL, APA PsycINFO and Cochrane Library) using terms for ACB and surgery. Grey literature and references from included studies will be searched for additional sources, with no limitations on publication date or language. All study designs will be eligible. Two independent reviewers will screen titles, abstracts and full texts in duplicate for eligibility. One reviewer will chart data, with a second reviewer validating the data charted. The findings will be synthesised, quantitatively summarised using descriptive statistics and qualitatively analysed through thematic analysis.

Ethics and dissemination
Ethics approval is not required as the study utilises published data. The dissemination of the findings will inform future research and improve understanding of the surgical care experiences of ACB patients. Dissemination will target academics and healthcare professionals through publications, presentations and workshops.

Primary prophylactic administration of G-CSF and loperamide resulted in a clinically relevant reduction of the incidence and severity of sacituzumab govitecan-related neutropenia and diarrhea.

3/o anno Fondazione Onda, servizi gratuiti clinico-diagnostici

3/o anno Fondazione Onda, servizi gratuiti clinico-diagnostici

3/o anno Fondazione Onda, servizi gratuiti clinico-diagnostici

Introduction
Biological disease modifying antirheumatic drugs (bDMARDs) have a central role in the treatment of rheumatoid arthritis (RA). Tumour necrosis factor inhibitors (TNFis) are commonly used as first-line agents, while non-TNFis (tocilizumab, abatacept and rituximab) have shown to be non-inferior to TNFis in head-to-head trials. In case of TNFi inadequate response, using other mechanisms of action provides a better response than using an alternate TNFi. Which non-TNFi bDMARD administered subcutaneously to allow for ambulatory management to choose in case of first line TNFi inadequate response has not been tested in a randomised clinical trial, while observational data support a potential superiority of tocilizumab over abatacept.

Methods and analysis
The SUNSTAR (SUbcutaNeouS Tocilizumab vs Abatacept in TNF Alpha inadequate responders for the treatment of Rheumatoid arthritis) study is a 52-week prospective, randomised, multicentre, open-label, superiority phase IV trial comparing subcutaneous tocilizumab with abatacept in a 1:1 ratio. Patients with active RA (Disease Activity Score-erythrocyte sedimentation rate >3.2 and Clinical Disease Activity Index (CDAI) >10) and with inadequate 3-month response to a first or second TNFi are included in 25 centres in France. The primary outcome is the CDAI improvement at week 24. Intention-to-treat analysis will be applied primarily. The secondary outcome is a composite outcome of the percentage of responders defined as a CDAI