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Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial

Por: Nevalainen · J. · Raitanen · J. · Natunen · K. · Kilpeläinen · T. · Rannikko · A. · Tammela · T. · Auvinen · A.
Introduction

Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.

The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening.

Methods

The trial aims to recruit at least 111 000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray’s test using intention-to-screen analysis of randomised men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening.

Ethics and dissemination

The trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (2910/2017). Results will be disseminated through publications in international peer-reviewed journals and at scientific meetings.

Trial registration number

NCT03423303

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service

Por: Kiely · D. G. · Hamilton · N. · Wood · S. · Durrington · C. · Exposto · F. · Muzwidzwa · R. · Raiteri · L. · Beaudet · A. · Muller · A. · Sauter · R. · Pillai · N. · Lawrie · A. · ASPIRE consortium · Condliffe · Elliot · Hameed · Charalampopoulos · Rothman · Roger Thompson · Hurdman
Objectives

This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH).

Design

Retrospective observational study.

Setting

Pulmonary hypertension referral centre in the UK.

Participants

Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis.

Primary and secondary outcome measures

Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed.

Results

Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6–18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients.

Conclusions

Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Impact of a pharmacy-led screening and intervention in people at risk of or living with chronic kidney disease in a primary care setting: a cluster randomised trial protocol

Por: Tesfaye · W. · Krass · I. · Sud · K. · Johnson · D. W. · Van · C. · Versace · V. L. · McMorrow · R. · Fethney · J. · Mullan · J. · Tran · A. · Robson · B. · Vagholkar · S. · Kairaitis · L. · Gisev · N. · Fathima · M. · Tong · V. · Coric · N. · Castelino · R. L.
Introduction

Chronic kidney disease (CKD) is increasingly recognised as a growing global public health problem. Early detection and management can significantly reduce the loss of kidney function. The proposed trial aims to evaluate the impact of a community pharmacy-led intervention combining CKD screening and medication review on CKD detection and quality use of medicines (QUM) for patients with CKD. We hypothesise that the proposed intervention will enhance detection of newly diagnosed CKD cases and reduce potentially inappropriate medications use by people at risk of or living with CKD.

Methods and analysis

This study is a multicentre, pragmatic, two-level cluster randomised controlled trial which will be conducted across different regions in Australia. Clusters of community pharmacies from geographical groups of co-located postcodes will be randomised. The project will be conducted in 122 community pharmacies distributed across metropolitan and rural areas. The trial consists of two arms: (1) Control Group: a risk assessment using the QKidney CKD risk assessment tool, and (2) Intervention Group: a risk assessment using the QKidney CKD plus Point-of-Care Testing for kidney function markers (serum creatinine and estimated glomerular filtration rate), followed by a QUM service. The primary outcomes of the study are the proportion of patients newly diagnosed with CKD at the end of the study period (12 months); and rates of changes in the number of medications considered problematic in kidney disease (number of medications prescribed at inappropriate doses based on kidney function and/or number of nephrotoxic medications) over the same period. Secondary outcomes include proportion of people on potentially inappropriate medications, types of recommendations provided by the pharmacist (and acceptance rate by general practitioners), proportion of people who were screened, referred, and took up the referral to visit their general practitioners, and economic and other patient-centred outcomes.

Ethics and dissemination

The trial protocol has been approved by the Human Research Ethics Committee at the University of Sydney (2022/044) and the findings of the study will be presented at scientific conferences and published in peer-reviewed journal(s).

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12622000329763).

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