Risultati per: Tumore prostata, test della saliva piu’ attendibile del PSA

Objectives
To evaluate the feasibility and reliability of hand-held ultrasound (HUD) examinations with real-time automatic decision-making software for ejection fraction (autoEF) and mitral annular plane systolic excursion (autoMAPSE) by novices (general practitioners), intermediate users (registered cardiac nurses) and expert users (cardiologists), respectively, compared to reference echocardiography by cardiologists in an outpatient cohort with suspected heart failure (HF).

Design
Feasibility study of a diagnostic test.

Setting and participants
166 patients with suspected HF underwent HUD examinations with autoEF and autoMAPSE measurements by five novices, three intermediate-skilled users and five experts. HUD results were compared with a reference echocardiography by experts. A blinded cardiologist scored all HUD recordings with automatic measurements as (1) discard, (2) accept, but adjust the measurement or (3) accept the measurement as it is.

Primary outcome measure
The feasibility of automatic decision-making software for quantification of left ventricular function.

Results
The users were able to run autoEF and autoMAPSE in most patients. The feasibility for obtaining accepted images (score of ≥2) with automatic measurements ranged from 50% to 91%. The feasibility was lowest for novices and highest for experts for both autoEF and autoMAPSE (p≤0.001). Large coefficients of variation and wide coefficients of repeatability indicate moderate agreement. The corresponding intraclass correlations (ICC) were moderate to good (ICC 0.51–0.85) for intra-rater and poor (ICC 0.35–0.51) for inter-rater analyses. The findings of modest to poor agreement and reliability were not explained by the experience of the users alone.

Conclusion
Novices, intermediate and expert users were able to record four-chamber views for automatic assessment of autoEF and autoMAPSE using HUD devices. The modest feasibility, agreement and reliability suggest this should not be implemented into clinical practice without further refinement and clinical evaluation.

Trial registration number
NCT03547076.

Introduction
Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.

Methods and analysis
In this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.

Ethics and dissemination
The study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study’s progress is monitored by Julius Clinical, a science-driven contract research organisation.

Trial registration number
EudraCT: 2017-003900-28.

Introduction
The Prostate Imaging Reporting and Data System (PI-RADS) standardises reporting of prostate MRI for the detection of clinically significant prostate cancer. We provide the protocol of a planned living systematic review and meta-analysis for (1) diagnostic accuracy (sensitivity and specificity), (2) cancer detection rates of assessment categories and (3) inter-reader agreement.

Methods and analysis
Retrospective and prospective studies reporting on at least one of the outcomes of interest are included. Each step that requires literature evaluation and data extraction is performed by two independent reviewers. Since PI-RADS is intended as a living document itself, a 12-month update cycle of the systematic review and meta-analysis is planned.
This protocol is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Protocols statement. The search strategies including databases, study eligibility criteria, index and reference test definitions, outcome definitions and data analysis processes are detailed. A full list of extracted data items is provided.
Summary estimates of sensitivity and specificity (for PI-RADS ≥3 and PI-RADS ≥4 considered positive) are derived with bivariate binomial models. Summary estimates of cancer detection rates are calculated with random intercept logistic regression models for single proportions. Summary estimates of inter-reader agreement are derived with random effects models.

Ethics and dissemination
No original patient data are collected, ethical review board approval, therefore, is not necessary. Results are published in peer-reviewed, open-access scientific journals. We make the collected data accessible as supplemental material to guarantee transparency of results.

PROSPERO registration number
CRD42022343931.

Introduction
Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods.

Methods and analysis
This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment (‘reference standard’). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response.

Ethics and dissemination
MALIMAR has ethical approval from South Central—Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination.

Trial registration number
NCT03574454.

New England Journal of Medicine, Volume 387, Issue 14, Page 1325-1328, October 2022.

This cohort study examines the association between maternal antipsychotic prescriptions filled during pregnancy and performance in standardized tests of mathematics and language among schoolchildren in Denmark.

Annals of Internal Medicine, Volume 175, Issue 10, Page 1366-1373, October 2022.

Introduction
Postoperative cognitive decline affects cognitive domains such as executive functions, memory, concentration and information processing. The analogue neuropsychological test developed by the International Study Group of Postoperative Cognitive Dysfunction (ISPOCD) is a well-established test for assessing cognitive performance. However, analogue tests are time-consuming, rarely cost-effective and can be at risk of administration bias. Digital solutions are comparable to analogue ones, have higher degrees of compliance and enable more standardised execution than analogue tests. Currently, there is a lack of recommendations for clinical evaluation of the patient’s cognition in the perioperative setting, standard care usually means no cognitive assessments prior or after the surgery. There is a need to find an equivalent neuropsychological test to the ISPOCD to make it accessible and easier to implement in a clinical context for perioperative patients. This study aims to examine how healthy seniors perform on two neuropsychological tests, analogue versus digital and measure equivalency between tests with correlation analysis.

Methods and analysis
This study will use a randomised cross-over design, including qualitative interviews regarding test experiences. Healthy participants ≥60 years of age will be eligible to participate in the study. Cognitive function will be measured by using the ISPOCD test and the Mindmore digital test. The participants will self-report depressive symptoms with the Geriatric Depression Scale-15, user experience of the digital test using a modified version of the System Usability Scale and answer questionnaires targeting their experiences after the tests. Furthermore, according to the Swedish Quality of Recovery Scale, self-reported concentration difficulties will also be measured.

Ethics and dissemination
The study has been approved by the Swedish Ethical Review Authority (Dnr 2021-05486-01) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, at scientific conferences, and in social media.

Trial registration number
2021-01095; ClinicalTrials.gov.

Objectives
The faecal immunochemical test (FIT) was introduced to triage patients with lower-risk symptoms of colorectal cancer (CRC) in English primary care in 2018. While there is growing evidence on its utility to triage patients in this setting, evidence is still limited on how official FIT guidance is being used, for which patients and for what symptoms. We aimed to investigate the use of FIT in primary care practice for lower-risk patients who did not immediately meet criteria for urgent referral.

Design
A prospective, descriptive study of symptomatic patients offered a FIT in primary care between January and June 2020.

Setting
East of England general practices.

Participants
Consenting patients (aged ≥40 years) who were seen by their general practitioners (GPs) with symptoms of possible CRC for whom a FIT was requested. We excluded patients receiving a FIT for asymptomatic screening purposes, or patients deemed by GPs as lacking capacity for informed consent. Data were obtained via patient questionnaire, medical and laboratory records.

Primary and secondary outcome measures
FIT results (10 µg Hb/g faeces defined a positive result); patient sociodemographic and clinical characteristics; patient-reported and GP-recorded symptoms, symptom severity and symptom agreement between patient and GP (% and kappa statistics).

Results
Complete data were available for 310 patients, median age 70 (IQR 61–77) years, 53% female and 23% FIT positive. Patients most commonly reported change in bowel habit (69%) and fatigue (57%), while GPs most commonly recorded abdominal pain (25%) and change in bowel habit (24%). Symptom agreement ranged from 44% (fatigue) to 80% (unexplained weight loss). Kappa agreement was universally low across symptoms.

Conclusion
Almost a quarter of this primary care cohort of symptomatic patients with FIT testing were found to be positive. However, there was low agreement between patient-reported and GP-recorded symptoms. This may impact cancer risk assessment and optimal patient management in primary care.

Objectives
To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training.

Design
Diagnostic test accuracy study.

Setting
Secondary care hospitals in Southern Vietnam.

Participants
DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion.

Primary and secondary outcome measures
Sensitivity was calculated at the two different time points, and 2 was used to test significance.

Results
In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8–42.2%) and improved in phase II after additional training was delivered (51.3–87.2%). The greatest improvement was seen among level 1 graders (p

Ultima volta del «concorsone» nazionale: dall’anno prossimo varranno le pre-selezioni già al liceo. Sempre che le elezioni non cambino lo scenario

This systematic review and meta-analysis compares the performance of the log-rank test vs the MaxCombo and difference in restricted mean survival time tests in immuno-oncology trials.

Introduction
Young febrile infants are at higher risk of invasive bacterial infections (IBIs) compared with older children. The clinical features of IBI are subtle in this cohort mandating that clinicians take a cautious approach to their initial assessment and management. This includes the measurement of blood biomarkers of infection such as C reactive protein (CRP) and procalcitonin (PCT). In the UK, PCT is not widely available and not recommended for routine use in hospital. This is in contrast to Europe and the USA where PCT is regularly used to assist clinical decision-making. The objective of this review and meta-analysis is to report the diagnostic test accuracy of PCT in detecting IBI in febrile infants less than 91 days old, compare its accuracy with CRP and define optimal PCT cut-off values in this cohort.

Methods and analysis
A search strategy will include MEDLINE, EMBASE, Web of Science, The Cochrane Library and grey literature. There will be no language or date limitations. Diagnostic accuracy studies compliant with STARD criteria will be considered against eligibility criteria. Abstracts, then full texts, of potentially eligible studies will be independently screened for selection. Data extraction and quality assessment, using the QUADAS-2 tool, will be completed by two independent authors and a third author used for any inconsistencies. True positives, false positives, true negatives and false negatives will be pooled to collate specificity and sensitivity with 95% CIs. Results will be portrayed in forest plots, alongside their quality assessments.

Ethics and dissemination
This review does not require ethical clearance. This review will be published in peer-reviewed journals and key messages will be disseminated through presentations at local and international conferences related to this field. The authors aim for this review to be completed and published in 2023.

A reduced rectoanal gradient, compared with age- and sex-matched asymptomatic individuals, was the most important parameter on anorectal manometry to predict impaired evacuation by balloon expulsion test or defecography and should be considered probable evidence of a defecatory disorder.

Objective
To estimate the effectiveness of messenger RNA (mRNA) booster doses during the period of Delta and Omicron variant dominance.

Design
We conducted a matched test-negative case–control study to estimate the vaccine effectiveness (VE) of three and two doses of mRNA vaccines against infection (regardless of symptoms) and against COVID-19-related hospitalisation and death.

Setting
Veterans Health Administration.

Participants
We used electronic health record data from 114 640 veterans who had a SARS-CoV-2 test during November 2021–January 2022. Patients were largely 65 years or older (52%), male (88%) and non-Hispanic white (59%).

Main outcome measures
First positive result for a SARS-CoV-2 PCR or antigen test.

Results
Against infection, booster doses had higher estimated VE (64%, 95% CI 63 to 65) than two-dose vaccination (12%, 95% CI 10 to 15) during the Omicron period. For the Delta period, the VE against infection was 90% (95% CI 88 to 92) among boosted vaccinees, higher than the VE among two-dose vaccinees (54%, 95% CI 50 to 57). Against hospitalisation, booster dose VE was 89% (95% CI 88 to 91) during Omicron and 94% (95% CI 90 to 96) during Delta; two-dose VE was 63% (95% CI 58 to 67) during Omicron and 75% (95% CI 69 to 80) during Delta. Against death, the VE with a booster dose was 94% (95% CI 90 to 96) during Omicron and 96% (95% CI 87 to 99) during Delta.

Conclusions
Among an older, mostly male, population with comorbidities, we found that an mRNA vaccine booster was highly effective against infection, hospitalisation and death. Although the effectiveness of booster vaccination against infection was moderately higher against Delta than against the Omicron SARS-CoV-2 variant, effectiveness against severe disease and death was similarly high against both variants.

Objective
To determine the test–retest reliability of the Brain Injury Screening Tool (BIST), which was designed to support the initial assessment of mild traumatic brain injury (mTBI) across a variety of contexts, including primary and secondary care.

Design
Test–retest design over a 2-week period.

Setting
Community based.

Participants
Sixty-eight adults (aged 18–58 years) who had not experienced an mTBI within the last 5 years and completed the BIST on two different occasions.

Measures
Participants were invited to complete the 15-item BIST symptom scale and the Depression, Anxiety and Stress Scale (DASS-21) online at two time-points (baseline and 2 weeks later). To account for large variations in mood affecting symptom reporting, change scores on the subscales of the DASS-21 were calculated, and outliers were removed from the analysis.

Results
The BIST total symptom score and subscale scores (physical-emotional, cognitive and vestibular) demonstrated moderate to good test–retest reliability with intraclass correlation coefficients ranging between 0.51 and 0.83. There were no meaningful differences between symptom reporting on the total scale or subscales of the BIST between time1 and time2 at the p