The trends in prostate specific antigen usage amongst United Kingdom urologists – a questionnaire based study

<p>Abstract</p> <p>Background</p> <p>Worldwide, the use of prostate specific antigen (PSA) testing as a screen for prostate cancer is contentious. Whilst there is no National UK Screening programme, many men undergo opportunistic screening. This study investigates UK urologist's usage of PSA and the awareness surrounding the Department of Health (DoH) PSA guidelines.</p> <p>Methods</p> <p>Urologists were sent a questionnaire regarding PSA cut-off values.</p> <p>Results</p> <p>Of the 733 urologists eligible to participate in this study 346 returned completed questionnaires giving a response rate of 47%. The most commonly generally used age-related PSA cut-off values (36% of respondents) are – 3.5 ng/ml for 50 – 59 year olds, 4.5 ng/ml for 60 – 69 year olds and 6.5 ng/ml for over 70 year olds. Two-thirds (58%, 200/346) of respondents were aware of the DoH PSA guidelines but only 20% (n = 69/346) follow these guidelines. The majority of respondents (68%, n = 234/346) used higher PSA cut-offs than recommended by the DoH. The level of compliance showed marked regional variation with a range from 7% to 44% (median 19%). In addition, it was apparent that lower PSA cut-off values were used in private practice as opposed to the National Health Service.</p> <p>Conclusion</p> <p>A nationwide lack of agreement on PSA cut-off values may generate a variable standard of care both regionally and in NHS versus private practice. Generally, higher PSA cut-off values are being used than recommended by the DoH guidance.</p

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Subnational mapping of under-5 and neonatal mortality trends in India: the Global Burden of Disease Study 2000-17

Background India has made substantial progress in improving child survival over the past few decades, but a comprehensive understanding of child mortality trends at disaggregated geographical levels is not available. We present a detailed analysis of subnational trends of child mortality to inform efforts aimed at meeting the India National Health Policy (NHP) and Sustainable Development Goal (SDG) targets for child mortality. Methods We assessed the under-5 mortality rate (U5MR) and neonatal mortality rate (NMR) from 2000 to 2017 in 5 × 5 km grids across India, and for the districts and states of India, using all accessible data from various sources including surveys with subnational geographical information. The 31 states and groups of union territories were categorised into three groups using their Socio-demographic Index (SDI) level, calculated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study on the basis of per-capita income, mean education, and total fertility rate in women younger than 25 years. Inequality between districts within the states was assessed using the coefficient of variation. We projected U5MR and NMR for the states and districts up to 2025 and 2030 on the basis of the trends from 2000 to 2017 and compared these projections with the NHP 2025 and SDG 2030 targets for U5MR (23 deaths and 25 deaths per 1000 livebirths, respectively) and NMR (16 deaths and 12 deaths per 1000 livebirths, respectively). We assessed the causes of child death and the contribution of risk factors to child deaths at the state level. Findings U5MR in India decreased from 83·1 (95% uncertainty interval [UI] 76·7–90·1) in 2000 to 42·4 (36·5–50·0) per 1000 livebirths in 2017, and NMR from 38·0 (34·2–41·6) to 23·5 (20·1–27·8) per 1000 livebirths. U5MR varied 5·7 times between the states of India and 10·5 times between the 723 districts of India in 2017, whereas NMR varied 4·5 times and 8·0 times, respectively. In the low SDI states, 275 (88%) districts had a U5MR of 40 or more per 1000 livebirths and 291 (93%) districts had an NMR of 20 or more per 1000 livebirths in 2017. The annual rate of change from 2010 to 2017 varied among the districts from a 9·02% (95% UI 6·30–11·63) reduction to no significant change for U5MR and from an 8·05% (95% UI 5·34–10·74) reduction to no significant change for NMR. Inequality between districts within the states increased from 2000 to 2017 in 23 of the 31 states for U5MR and in 24 states for NMR, with the largest increases in Odisha and Assam among the low SDI states. If the trends observed up to 2017 were to continue, India would meet the SDG 2030 U5MR target but not the SDG 2030 NMR target or either of the NHP 2025 targets. To reach the SDG 2030 targets individually, 246 (34%) districts for U5MR and 430 (59%) districts for NMR would need a higher rate of improvement than they had up to 2017. For all major causes of under-5 death in India, the death rate decreased between 2000 and 2017, with the highest decline for infectious diseases, intermediate decline for neonatal disorders, and the smallest decline for congenital birth defects, although the magnitude of decline varied widely between the states. Child and maternal malnutrition was the predominant risk factor, to which 68·2% (65·8–70·7) of under-5 deaths and 83·0% (80·6–85·0) of neonatal deaths in India could be attributed in 2017; 10·8% (9·1–12·4) of under-5 deaths could be attributed to unsafe water and sanitation and 8·8% (7·0–10·3) to air pollution. Interpretation India has made gains in child survival, but there are substantial variations between the states in the magnitude and rate of decline in mortality, and even higher variations between the districts of India. Inequality between districts within states has increased for the majority of the states. The district-level trends presented here can provide crucial guidance for targeted efforts needed in India to reduce child mortality to meet the Indian and global child survival targets. District-level mortality trends along with state-level trends in causes of under-5 and neonatal death and the risk factors in this Article provide a comprehensive reference for further planning of child mortality reduction in India