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Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7-15·1%), and stages 3-5 was 10·6%(9·2-12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8-4·2%); Stage-2 (eGFR 60-89+ACR>30): 3·9% (2·7-5·3%); Stage-3 (eGFR 30-59): 7·6% (6·4-8·9%); Stage-4 = (eGFR 29-15): 0·4% (0·3-0·5%); and Stage-5 (eGFR<15): 0·1% (0·1-0·1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes.

Objectives To assess diagnostic accuracy of screening tests for pre-diabetes and efficacy of interventions (lifestyle or metformin) in preventing onset of type 2 diabetes in people with pre-diabetes.Design Systematic review and meta-analysis.Data sources and method Medline, PreMedline, and Embase. Study protocols and seminal papers were citation-tracked in Google Scholar to identify definitive trials and additional publications. Data on study design, methods, and findings were extracted onto Excel spreadsheets; a 20% sample was checked by a second researcher. Data extracted for screening tests included diagnostic accuracy and population prevalence. Two meta-analyses were performed, one summarising accuracy of screening tests (with the oral glucose tolerance test as the standard) for identification of pre-diabetes, and the other assessing relative risk of progression to type 2 diabetes after either lifestyle intervention or treatment with metformin.Eligibility criteria Empirical studies evaluating accuracy of tests for identification of pre-diabetes. Interventions (randomised trials and interventional studies) with a control group in people identified through screening. No language restrictions.Results 2874 titles were scanned and 148 papers (covering 138 studies) reviewed in full. The final analysis included 49 studies of screening tests (five of which were prevalence studies) and 50 intervention trials. HbA1c had a mean sensitivity of 0.49 (95% confidence interval 0.40 to 0.58) and specificity of 0.79 (0.73 to 0.84), for identification of pre-diabetes, though different studies used different cut-off values. Fasting plasma glucose had a mean sensitivity of 0.25 (0.19 to 0.32) and specificity of 0.94 (0.92 to 0.96). Different measures of glycaemic abnormality identified different subpopulations (for example, 47%of people with abnormal HbA1c had no other glycaemic abnormality). Lifestyle interventions were associated with a 36% (28% to 43%) reduction in relative risk of type 2 diabetes over six months to six years, attenuating to 20% (8% to 31%) at follow-up in the period after the trails.Conclusions HbA1c is neither sensitive nor specific for detecting pre-diabetes; fasting glucose is specific but not sensitive. Interventions in people classified through screening as having pre-diabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial populations. As screening is inaccurate, many people will receives an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention. These findings suggest that “screen and treat” policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes.Registration PROSPERO (No CRD42016042920).

The aim of this systematic review was to summarize national and international guidelines that made recommendations for monitoring patients diagnosed with low-risk cancer. It appraised the quality of guidelines and determined whether the guidelines adequately identified patients for monitoring, specified which tests to use, defined monitoring intervals, and stated triggers for further intervention. It then assessed the evidence to support each recommendation. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched PubMed and Turning Research into Practice databases for national and international guidelines' that were written in English and developed or updated between 2012 and 2023. Quality of individual guidelines was assessed using the AGREE II tool. Across the 41 published guidelines, 48 different recommendations were identified: 15 (31%) for prostate cancer, 11 (23%) for renal cancer, 6 (12.5%) for thyroid cancer, and 10 (21%) for blood cancer. The remaining 6 (12.5%) were for brain, gastrointestinal, oral cavity, bone and pheochromocytoma and paraganglioma cancer. When combining all guidelines, 48 (100%) stated which patients qualify for monitoring, 31 (65%) specified which tests to use, 25 (52%) provided recommendations for surveillance intervals, and 23 (48%) outlined triggers to initiate intervention. Across all cancer sites, there was a strong positive trend with higher levels of evidence being associated with an increased likelihood of a recommendation being specific (P = 0.001) and the evidence for intervals was based on expert opinion or other guidance. With the exception of prostate cancer, the evidence base for monitoring low-risk cancer is weak and consequently recommendations in clinical guidelines are inconsistent. There is a lack of direct evidence to support monitoring recommendations in the literature making guideline developers reliant on expert opinion, alternative guidelines, or indirect or nonspecific evidence. •Monitoring guidelines focus on eligibility and tests more than intervals or triggers.•Prostate cancer is the only cancer site supported by randomized control evidence.•Monitoring interval recommendations vary due to expert opinion and indirect evidence.•Direct evidence for surveillance intervals and triggers are required.•Cohort studies offer a solution when randomized trials are impractical.

Current UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine. We constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses. Between Dec 8, 2020, and Feb 28, 2022, 17 337 580 individuals completed their primary vaccine schedule and 14 698 030 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·3%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs female; 1·23 [1·20–1·26]), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53–6·09])—and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90–4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]). Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics. National Core Studies–Immunity, UK Research and Innovation (Medical Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Background We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines. Methods This retrospective matched cohort study used cancer registry linked electronic health records from the UK’s Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage. Results In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88–3.73)) and women (1.87 (1.68–2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3–24 months after presenting with UWL, cancer diagnosis was less likely than in comparators. Conclusion UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.

The NHS Long Term Plan for cancer aims to increase early-stage diagnoses from 50% to 75% and to have 55,000 more people each year survive their cancer for at least 5 years following diagnosis. The targets measures are flawed and could be met without improving outcomes that really matter to patients. The proportion of early-stage diagnoses could increase, while the number of patients presenting at a late-stage remains the same. More patients could survive their cancer for longer, but lead time and overdiagnosis bias make it impossible to know whether anyone had their life prolonged. The target measures should switch from biased case-based measures to unbiased population-based measures that reflect the key objectives in cancer care: reducing late-stage incidence and mortality.

AbstractObjectiveTo characterise the use of the prostate specific antigen (PSA) test in primary care in England.DesignPopulation based open cohort study.SettingEngland.Participants10 235 805 male patients older than 18 years and registered at 1442 general practices that contributed to the Clinical Practice Research Datalink between 2000 and 2018. Data were linked to the National Cancer Registry, Hospital Episode Statistics, and Office for National Statistics.Main outcome measuresPopulation based temporal trends and annual percentage changes were analysed using age standardised PSA testing rates. Mixed effects negative binomial regression models investigated individual patient rate ratios of PSA testing. Linear mixed effects models examined factors associated with an individual patient’s length of PSA retesting intervals. All results were analysed by region, deprivation, age, ethnicity, family history of prostate cancer, symptom presentation, and PSA value.Results1 521 116 patients had at least one PSA test, resulting in 3 835 440 PSA tests overall. 48.4% (735 750) of these patients had multiple tests and 72.8% (535 990) of them never presented with a PSA value above the age specific referral threshold. The median retesting interval overall was 12.6 months (interquartile range 6.2-27.5). Testing rates varied by region, deprivation, ethnicity, family history, age, PSA value, and symptoms. Once tested, patients had shorter retesting intervals if they were older, were of an ethnicity other than white, had a family history of prostate cancer, or had previously raised PSA levels. Despite considerable variation in testing rates by region and deprivation, the length of retesting intervals was similar across these groups.ConclusionsPSA testing before a diagnosis of prostate cancer in primary care in England varied. Among patients who underwent multiple tests, many were tested more frequently than recommended, raising concerns about overtesting. PSA retesting is occurring in patients without recorded symptoms and in those with low PSA values. To ensure maximum benefit to patients while reducing the risk of overtesting, research is urgently needed to determine appropriate evidence based PSA retesting intervals.

AbstractObjectivesTo quantify and compare the rate of weight regain after cessation of weight management medications (WMMs) in adults with overweight or obesity.DesignSystematic review and meta-analysis.Study selectionTrial registries and databases (Medline, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries) were searched from inception until February 2025 for randomised controlled trials (RCTs), non-randomised trials, and observational studies that included WMM (≥8 weeks) with follow-up for ≥4 weeks after cessation of treatment in adults with overweight or obesity. Comparators were any non-drug weight loss intervention or placebo.Data extraction and synthesisThe review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Two independent reviewers screened titles, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for RCTs and the ROBINS-I tool for non-randomised trials. Data were analysed using mixed effect, meta-regression, and time-to-event models. Weight regain after cessation of WMM was compared with that reported after cessation of behavioural weight management programmes (BWMPs).Main outcome measuresThe primary outcome was rate of weight regain from end of treatment, with associated changes in cardiometabolic markers as a secondary outcome.ResultsOf the 9288 titles screened, 37 studies (63 intervention arms, 9341 participants) were included. Average treatment duration was 39 (range 11-176) weeks, with average follow-up of 32 (4-104) weeks. The average monthly rate of weight regain was 0.4 kg (95% confidence interval (CI) 0.3 to 0.5) (mixed model 0.3 kg (0.2 to 0.4) monthly v control in RCTs). All cardiometabolic markers were projected to return to baseline within 1.4 years after the cessation of WMM. Weight regain was faster after WMM than after BWMP (by 0.3 kg (0.22 to 0.34) monthly), independent of initial weight loss. Estimates and precision were robust in sensitivity analyses.ConclusionsThis review found that cessation of WMM is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers. Regain after WMM was faster than after BWMP. These findings suggest caution in short term use of these drugs without a more comprehensive approach to weight management.Systematic review registrationPROSPERO CRD42024532069.

Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care. We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites. 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4–73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5–80·1), negative predictive value of 97·6% (97·1–98·0), sensitivity of 66·3% (61·2–71·1), and specificity of 98·4% (98·1–98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0–34·1) in stage I to 95·3% (88·5–98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 84·8% (95% CI 79·5–89·0) of cases. Sensitivity 80·4% (95% CI 66·1–90·6) and negative predictive value 99·1% (98·2–99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer. This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms. GRAIL Bio UK.