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 metaanalyses 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.
\n \n\n \n \nAims Clinical trial patients are highly motivated but may encounter difficulty in taking study medication regularly when treatment burden is substantial. We assessed a brief behavioural intervention, given in addition to a standard trial protocol. Methods We performed a two-arm adherence sub-study within a twelve-month randomised controlled drug trial evaluating the impact of statin and/or omega-3 EE90 treatment in 800 patients with type 2 diabetes. Fifty-nine United Kingdom general practices were cluster-randomised to action-planning or control groups. The former delivered an initial written exercise prompting participants to formulate action-plans to take study medication regularly, with brief nurse encouragement to use action-plans at later visits, whilst the latter followed the standard trial protocol. The primary outcome was proportion of days on which study medication were taken as intended measured by electronic medication containers. Results Adjusted mean (95% CI) proportion of days with medication taken as intended was 79.3% (76.3\u201382.3%) for the 30 action-planning practices (321 participants), compared with 78.5% (75.8\u201381.1%) for 27 control group practices (426 participants, with a mean intervention effect of 0.9%, 95% CI \u22123.1% to +4.9%, p = 0.67). Adjusted odds ratios for \u2a7e80% trial medication adherence for action-planning compared with control practices were 1.29 (0.90\u20131.84) and 1.38 (0.96\u20131.99) respectively. Conclusions Low-intensity action-planning interventions used alone are unlikely to have a clinically important impact on medication adherence, particularly in a clinical trial setting. These findings, do not exclude their contribution, as part of a multifactorial intervention, to improving treatment adherence. ISRCTN number 76737502.
\n \n\n \n \nChronic 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.
\n \n\n \n \nBackground The 2015 NICE guidelines for suspected cancer recommend that English General Practitioners have direct access to diagnostic tests to investigate symptoms of cancer that do not meet the criteria for urgent referral. We aimed to identify the proportion of GPs in England with direct access to these tests. Methods We recruited 533 English GPs through a national clinical research network to complete an online survey about direct access to laboratory, radiology, and endoscopy tests in the three months leading up to the release of the 2015 NICE guidance. If they had direct access to a diagnostic test, GPs were asked about the time necessary to arrange a test and receive a report. Results are reported by NHS sub-region and, adjusting for sampling, for England as a whole. Results Almost all GPs reported direct access to x-ray and laboratory investigations except faecal occult blood testing (54%, 95% CI 49-59%) and urine protein electrophoresis (89%, 95% CI 84-92%). Fewer GPs had direct access to CT scans (54%, 95% CI 49-59%) or endoscopy (colonoscopy 32%, 95% CI 28-37%; gastroscopy 72%, 95% CI 67-77%). There was significant variation in direct access between NHS regions for the majority of imaging tests-for example, from 20 to 85% to MRI. Apart from x-ray, very few GPs (1-22%) could access radiology and endoscopy within the timescales recommended by NICE. The modal request to test time was 2-4 weeks for routine radiology and 4-6 weeks for routine endoscopy with results taking another 1-2 weeks. Conclusion At the time that the 2015 NICE guideline was released, local investment was required to not only provide direct access but also reduce the interval between request and test and speed up reporting. Further research using our data as a benchmark is now required to identify whether local improvements in direct access have been achieved in response to the NICE targets. If alternative approaches to test access are to be proposed they must be piloted comprehensively and underpinned by robust effectiveness data.
\n \n\n \n \nBackground: The English NHS Diabetic Eye Screening Programme was established in 2003. Eligible people are invited annually for digital retinal photography screening. Those found to have potentially sight-threatening diabetic retinopathy (STDR) are referred to surveillance clinics or to Hospital Eye Services. Objectives: To determine whether personalised screening intervals are cost-effective. Design: Risk factors were identified in Gloucestershire, UK using survival modelling. A probabilistic decision hidden (unobserved) Markov model with a misgrading matrix was developed. This informed estimation of lifetime costs and quality-adjusted life-years (QALYs) in patients without STDR. Two personalised risk stratification models were employed: two screening episodes (SEs) (low, medium or high risk) or one SE with clinical information (low, medium\u2013low, medium\u2013high or high risk). The risk factor models were validated in other populations. Setting: Gloucestershire, Nottinghamshire, South London and East Anglia (all UK). Participants: People with diabetes in Gloucestershire with risk stratification model validation using data from Nottinghamshire, South London and East Anglia. Main outcome measures: Personalised risk-based algorithm for screening interval; cost-effectiveness of different screening intervals. Results: Data were obtained in Gloucestershire from 12,790 people with diabetes with known risk factors to derive the risk estimation models, from 15,877 people to inform the uptake of screening and from 17,043 people to inform the health-care resource-usage costs. Two stratification models were developed: one using only results from previous screening events and one using previous screening and some commonly available GP data. Both models were capable of differentiating groups at low and high risk of development of STDR. The rate of progression to STDR was 5 per 1000 person-years (PYs) in the lowest decile of risk and 75 per 1000 PYs in the highest decile. In the absence of personalised risk stratification, the most cost-effective screening interval was to screen all patients every 3 years, with a 46% probability of this being cost-effective at a \u00a330,000 per QALY threshold. Using either risk stratification models, screening patients at low risk every 5 years was the most cost-effective option, with a probability of 99-100% at a \u00a330,000 per QALY threshold. For the medium-risk groups screening every 3 years had a probability of 43 \u201348% while screening high-risk groups every 2 years was cost-effective with a probability of 55\u201359%. Conclusions: The study found that annual screening of all patients for STDR was not cost-effective. Screening this entire cohort every 3 years was most likely to be cost-effective. When personalised intervals are applied, screening those in our low-risk groups every 5 years was found to be cost-effective. Screening high-risk groups every 2 years further improved the cost-effectiveness of the programme. There was considerable uncertainty in the estimated incremental costs and in the incremental QALYs, particularly with regard to implications of an increasing proportion of maculopathy cases receiving intravitreal injection rather than laser treatment. Future work should focus on improving the understanding of risk, validating in further populations and investigating quality issues in imaging and assessment including the potential for automated image grading.
\n \n\n \n \nObjectives To describe the level of overdetection people would find acceptable in screening for breast, prostate, and bowel cancer and whether acceptability is influenced by the magnitude of the benefit from screening and the cancer specific harms from overdetection. Design Online survey. Women were presented with scenarios on breast and bowel cancer, men with scenarios on prostate and bowel cancer. For each particular cancer, we presented epidemiological information and described the treatment and its consequences. Secondly, we presented two different scenarios of benefit: one indicating a 10% reduction in cancer specific mortality and the second indicating a 50% reduction. Setting Online survey of the population in the United Kingdom. Participants Respondents were part of an existing panel of people who volunteer for online research and were invited by email or online marketing. We recruited 1000 respondents, representative for age and sex for the UK population. Main outcome measures Number of cases of overdetection people were willing to accept, ranging from 0-1000 (complete screened population) for each cancer modality and each scenario of benefit. Results There was large variability between respondents in the level of overdetection they would find acceptable, with medians ranging from 113 to 313 cases of overdetection per 1000 people screened. Across all scenarios, 4-7% of respondents indicated they would accept no overdetection at all compared with 7-14% who thought that it would be acceptable for the entire screened population to be overdetected. Acceptability in screening for bowel cancer was significantly lower than for breast and prostate cancer. People aged 50 or over accepted significantly less overdetection, whereas people with higher education levels accepted more; 29% of respondents had heard of overdetection before. Conclusions Acceptability of overdetection in cancer screening is variable. Invitations for screening should include clear information on the likelihood and consequences of overdetection to allow people to make an informed choice.
\n \n\n \n \nBackground: Failure to take medication reduces the effectiveness of treatment leading to increased morbidity and mortality. We evaluated the efficacy of a consultation-based intervention to support objectively-assessed adherence to oral glucose lowering medication (OGLM) compared to usual care among people with type 2 diabetes. Methods. This was a parallel group randomised trial in adult patients with type 2 diabetes and HbA1c7.5% (58 mmol/mol), prescribed at least one OGLM. Participants were allocated to a clinic nurse delivered, innovative consultation-based intervention to strengthen patient motivation to take OGLM regularly and support medicine taking through action-plans, or to usual care. The primary outcome was the percentage of days on which the prescribed dose of medication was taken, measured objectively over 12 weeks with an electronic medication-monitoring device (TrackCap, Aardex, Switzerland). The primary analysis was intention-to-treat. Results: 211 patients were randomised between July 1, 2006 and November 30, 2008 in 13 British general practices (primary care clinics). Primary outcome data were available for 194 participants (91.9%). Mean (sd) percentage of adherent days was 77.4% (26.3) in the intervention group and 69.0% (30.8) in standard care (mean difference between groups 8.4%, 95% confidence interval 0.2% to 16.7%, p=0.044). There was no significant adverse impact on functional status or treatment satisfaction. Conclusions: This well-specified, theory based intervention delivered in a single session of 30 min in primary care increased objectively measured medication adherence, with no adverse effect on treatment satisfaction. These findings justify a definitive trial of this approach to improving medication adherence over a longer period of time, with clinical and cost-effectiveness outcomes to inform clinical practice. Trial registration. Current Controlled Trials ISRCTN30522359. \u00a9 2012 Farmer et al.; licensee BioMed Central Ltd.
\n \n\n \n \nIntroduction Electronic cigarettes (ECs) and heated tobacco products (HTPs) are recent arrivals to the nicotine product market in the Middle East, which are rapidly growing in popularity in the region. There is a lack of surveillance data at the country-level on use of these products and factors associated with their use. Aims and Methods This study analyzed a subset of data from the United Arab Emirates Healthy Future Study, a population-based cohort study of the Emirati population, to determine the factors associated with EC and HTP use among a sample of Emirati adults (\u226518 years). The baseline assessment and supplementary questionnaires, conducted from 2016 to 2023, included data on combustible tobacco use, EC, and HTP use and sociodemographic characteristics. Results Of the 2041 individuals who answered questions on EC use, 32% reported ever using them. Of the 521 people who provided data on HTP, 30% reported ever using them. After adjusting for age, sex, education, perceived harms, and perceived addictiveness of EC, current EC use was associated with baseline combustible tobacco smoking (aOR = 27.63, 95% confidence interval [CI] 14.39, 53.06), users of a younger age (aOR = 0.91, 95% CI = 0.88, 0.95), and users of male sex (OR = 2.15, 95% CI = 1.21, 3.81). Current HTP use was less common but was also associated with baseline combustible tobacco use. Conclusions The use of ECs and HTPs was more common among those who used combustible tobacco. Future research should examine use trajectories among those who do and do not smoke, as well as the uptake of these products among youth. Implications Non-combustible nicotine products are growing in popularity in the Middle East Region. Our study found that EC and HTP use is associated with baseline combustible tobacco use and that concurrent users may use them to cut down on their combustible tobacco use. Continued comprehensive population-based monitoring of all-tobacco and nicotine products, especially EC and HTP use, will provide current data to aid in appropriately informing public health and harm reduction messages and programming
\n \n\n \n \nBackground: Blood tests used to identify patients at increased risk of undiagnosed cancer are commonly used in isolation, primarily by monitoring whether results fall outside the normal range. Some prediction models incorporate changes over repeated blood tests (or trends) to improve individualized cancer risk identification, as relevant trends may be confined within the normal range. Objective: Our aim was to critically appraise existing diagnostic prediction models incorporating blood test trends for the risk of cancer. Methods: MEDLINE and EMBASE were searched until April 3, 2025 for diagnostic prediction model studies using blood test trends for cancer risk. Screening was performed by 4 reviewers. Data extraction for each article was performed by 2 reviewers independently. To critically appraise models, we narratively synthesized studies, including model building and validation strategies, model reporting, and the added value of blood test trends. We also reviewed the performance measures of each model, including discrimination and calibration. We performed a random-effects meta-analysis of the c-statistic for a trends-based prediction model if there were at least 3 studies validating the model. The risk of bias was assessed using the PROBAST (prediction model risk of bias assessment tool). Results: We included 16 articles, with a total of 7 models developed and 14 external validation studies. In the 7 models derived, full blood count (FBC) trends were most commonly used (86%, n=7 models). Cancers modeled were colorectal (43%, n=3), gastro-intestinal (29%, n=2), nonsmall cell lung (14%, n=1), and pancreatic (14%, n=1). In total, 2 models used statistical logistic regression, 2 used joint modeling, and 1 each used XGBoost, decision trees, and random forests. The number of blood test trends included in the models ranged from 1 to 26. A total of 2 of 4 models were reported with the full set of coefficients needed to predict risk, with the remaining excluding at least one coefficient from their article or were not publicly accessible. The c-statistic ranged 0.69\u20100.87 among validation studies. The ColonFlag model using trends in the FBC was commonly externally validated, with a pooled c-statistic=0.81 (95% CI 0.77-0.85; n=4 studies) for 6-month colorectal cancer risk. Models were often inadequately tested, with only one external validation study assessing model calibration. All 16 studies scored a low risk of bias regarding predictor and outcome details. All but one study scored a high risk of bias in the analysis domain, with most studies often removing patients with missing data from analysis or not adjusting the derived model for overfitting. Conclusions: Our review highlights that blood test trends may inform further investigation for cancer. However, models were not available for most cancer sites, were rarely externally validated, and rarely assessed calibration when they were externally validated.
\n \n\n \n \nClinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient\u2019s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.
\n \n\n \n \nChildhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P
\n \n\n \n \nBackground: Evidence for kidney function monitoring intervals in primary care is weak, and based mainly on expert opinion. In the absence of trials of monitoring strategies, an approach combining a model for the natural history of kidney function over time combined with a cost-effectiveness analysis offers the most feasible approach for comparing the effects of monitoring under a variety of policies. This study aimed to create a model for kidney disease progression using routinely collected measures of kidney function. Methods: This is an open cohort study of patients aged \u226518 years, registered at 643 UK general practices contributing to the Clinical Practice Research Datalink between 1 April 2005 and 31 March 2014. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Hidden Markov models for estimated glomerular filtration rate (eGFR) stage progression were fitted to four patient cohorts defined by baseline albuminuria stage; adjusted for sex, history of heart failure, cancer, hypertension and diabetes, annually updated for age. Results: Of 1,973,068 patients, 1,921,949 had no recorded urine albumin at baseline, 37,947 had normoalbuminuria (<3mg/mmol), 10,248 had microalbuminuria (3-30mg/mmol), and 2,924 had macroalbuminuria (>30mg/mmol). Estimated annual transition probabilities were 0.75-1.3%, 1.5-2.5%, 3.4-5.4% and 3.1-11.9% for each cohort, respectively. Misclassification of eGFR stage was estimated to occur in 12.1% (95%CI: 11.9-12.2%) to 14.7% (95%CI: 14.1-15.3%) of tests. Male gender, cancer, heart failure and age were independently associated with declining renal function, whereas the impact of raised blood pressure and glucose on renal function was entirely predicted by albuminuria. Conclusions: True kidney function deteriorates slowly over time, declining more sharply with elevated urine albumin, increasing age, heart failure, cancer and male gender. Consecutive eGFR measurements should be interpreted with caution as observed improvement or deterioration may be due to misclassification.
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