-
1.
Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis.
Wu, Y, Levis, B, Riehm, KE, Saadat, N, Levis, AW, Azar, M, Rice, DB, Boruff, J, Cuijpers, P, Gilbody, S, et al
Psychological medicine. 2020;(8):1368-1380
-
-
Free full text
-
Abstract
BACKGROUND Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. METHODS We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. RESULTS 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). CONCLUSIONS PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
-
2.
Performance of deep neural network-based artificial intelligence method in diabetic retinopathy screening: a systematic review and meta-analysis of diagnostic test accuracy.
Wang, S, Zhang, Y, Lei, S, Zhu, H, Li, J, Wang, Q, Yang, J, Chen, S, Pan, H
European journal of endocrinology. 2020;(1):41-49
Abstract
OBJECTIVE Automatic diabetic retinopathy screening system based on neural networks has been used to detect diabetic retinopathy (DR). However, there is no quantitative synthesis of performance of these methods. We aimed to estimate the sensitivity and specificity of neural networks in DR grading. METHODS Medline, Embase, IEEE Xplore, and Cochrane Library were searched up to 23 July 2019. Studies that evaluated performance of neural networks in detection of moderate or worse DR or diabetic macular edema using retinal fundus images with ophthalmologists' judgment as reference standard were included. Two reviewers extracted data independently. Risk of bias of eligible studies was assessed using QUDAS-2 tool. RESULTS Twenty-four studies involving 235 235 subjects were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed a pooled sensitivity of 91.9% (95% CI: 89.6% to 94.3%) and specificity of 91.3% (95% CI: 89.0% to 93.5%). Subgroup analyses and meta-regression did not provide any statistically significant findings for the heterogeneous diagnostic accuracy in studies with different image resolutions, sample sizes of training sets, architecture of convolutional neural networks, or diagnostic criteria. CONCLUSIONS State-of-the-art neural networks could effectively detect clinical significant DR. To further improve diagnostic accuracy of neural networks, researchers might need to develop new algorithms rather than simply enlarge sample sizes of training sets or optimize image quality.
-
3.
The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.
He, C, Levis, B, Riehm, KE, Saadat, N, Levis, AW, Azar, M, Rice, DB, Krishnan, A, Wu, Y, Sun, Y, et al
Psychotherapy and psychosomatics. 2020;(1):25-37
-
-
Free full text
-
Abstract
BACKGROUND Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. OBJECTIVE To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. METHODS Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. RESULTS Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). CONCLUSIONS The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.
-
4.
Single-Field Non-Mydriatic Fundus Photography for Diabetic Retinopathy Screening: A Systematic Review and Meta-Analysis.
Hu, J, Chen, R, Lu, Y, Dou, X, Ye, B, Cai, Z, Pu, Z, Mou, L
Ophthalmic research. 2019;(2):61-67
Abstract
PURPOSE Single-field non-mydriatic fundus photography (NMFP) has been used to detect diabetic retinopathy (DR) in many studies; however, its value in a general clinical setting has not been established. Here we performed a meta-analysis to evaluate its diagnostic effectiveness. METHOD We systematically searched PubMed, EMBASE, and Cochrane databases for candidate studies published through May 19, 2018. A random-effect model was used to calculate the diagnostic indicators including the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence intervals. RESULTS Ten prospective studies were ultimately included. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.68, 0.94, 11.2, 0.34 and 33, respectively. The AUC was 0.88. Subgroup analysis showed that single-field NMFP had a respective sensitivity and specificity of 0.73 and 0.91 when compared to standard 7-field mydriatic stereoscopic photography (7SF), and 0.54 and 0.98 when compared to slit-lamp biomicroscopy as reference standard. CONCLUSIONS Single-field NMFP is inadequate to detect DR. Additionally, it showed higher sensitivity and lower specificity when 7SF was used as reference standard, as compared to slit-lamp biomicroscopy, suggesting that different reference standards used in DR screening might have affected the diagnostic results.
-
5.
Screening for gestational diabetes mellitus based on different risk profiles and settings for improving maternal and infant health.
Tieu, J, McPhee, AJ, Crowther, CA, Middleton, P, Shepherd, E
The Cochrane database of systematic reviews. 2017;(8):CD007222
-
-
Free full text
-
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mothers and their infants in the short and long term. There is strong evidence to support treatment for GDM. However, there is uncertainty as to whether or not screening all pregnant women for GDM will improve maternal and infant health and if so, the most appropriate setting for screening. This review updates a Cochrane Review, first published in 2010, and subsequently updated in 2014. OBJECTIVES To assess the effects of screening for gestational diabetes mellitus based on different risk profiles and settings on maternal and infant outcomes. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register (31 January 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (14 June 2017), and reference lists of retrieved studies. SELECTION CRITERIA We included randomised and quasi-randomised trials evaluating the effects of different protocols, guidelines or programmes for screening for GDM based on different risk profiles and settings, compared with the absence of screening, or compared with other protocols, guidelines or programmes for screening. We planned to include trials published as abstracts only and cluster-randomised trials, but we did not identify any. Cross-over trials are not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included trials. We resolved disagreements through discussion or through consulting a third reviewer. MAIN RESULTS We included two trials that randomised 4523 women and their infants. Both trials were conducted in Ireland. One trial (which quasi-randomised 3742 women, and analysed 3152 women) compared universal screening versus risk factor-based screening, and one trial (which randomised 781 women, and analysed 690 women) compared primary care screening versus secondary care screening. We were not able to perform meta-analyses due to the different interventions and comparisons assessed.Overall, there was moderate to high risk of bias due to one trial being quasi-randomised, inadequate blinding, and incomplete outcome data in both trials. We used GRADEpro GDT software to assess the quality of the evidence for selected outcomes for the mother and her child. Evidence was downgraded for study design limitations and imprecision of effect estimates. Universal screening versus risk-factor screening (one trial) MotherMore women were diagnosed with GDM in the universal screening group than in the risk-factor screening group (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.12 to 3.04; participants = 3152; low-quality evidence). There were no data reported under this comparison for other maternal outcomes including hypertensive disorders of pregnancy, caesarean birth, perineal trauma, gestational weight gain, postnatal depression, and type 2 diabetes. ChildNeonatal outcomes: large-for-gestational age, perinatal mortality, mortality or morbidity composite, hypoglycaemia; and childhood/adulthood outcomes: adiposity, type 2 diabetes, and neurosensory disability, were not reported under this comparison. Primary care screening versus secondary care screening (one trial) MotherThere was no clear difference between the primary care and secondary care screening groups for GDM (RR 0.91, 95% CI 0.50 to 1.66; participants = 690; low-quality evidence), hypertension (RR 1.41, 95% CI 0.77 to 2.59; participants = 690; low-quality evidence), pre-eclampsia (RR 0.80, 95% CI 0.36 to 1.78; participants = 690;low-quality evidence), or caesarean section birth (RR 1.00, 95% CI 0.80 to 1.27; participants = 690; low-quality evidence). There were no data reported for perineal trauma, gestational weight gain, postnatal depression, or type 2 diabetes. ChildThere was no clear difference between the primary care and secondary care screening groups for large-for-gestational age (RR 1.37, 95% CI 0.96 to 1.96; participants = 690; low-quality evidence), neonatal complications: composite outcome, including: hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, shoulder dystocia, five minute Apgar less than seven at one or five minutes, prematurity (RR 0.99, 95% CI 0.57 to 1.71; participants = 690; low-quality evidence), or neonatal hypoglycaemia (RR 1.10, 95% CI 0.28 to 4.38; participants = 690; very low-quality evidence). There was one perinatal death in the primary care screening group and two in the secondary care screening group (RR 1.10, 95% CI 0.10 to 12.12; participants = 690; very low-quality evidence). There were no data for neurosensory disability, or childhood/adulthood adiposity or type 2 diabetes. AUTHORS' CONCLUSIONS There are insufficient randomised controlled trial data evaluating the effects of screening for GDM based on different risk profiles and settings on maternal and infant outcomes. Low-quality evidence suggests universal screening compared with risk factor-based screening leads to more women being diagnosed with GDM. Low to very low-quality evidence suggests no clear differences between primary care and secondary care screening, for outcomes: GDM, hypertension, pre-eclampsia, caesarean birth, large-for-gestational age, neonatal complications composite, and hypoglycaemia.Further, high-quality randomised controlled trials are needed to assess the value of screening for GDM, which may compare different protocols, guidelines or programmes for screening (based on different risk profiles and settings), with the absence of screening, or with other protocols, guidelines or programmes. There is a need for future trials to be sufficiently powered to detect important differences in short- and long-term maternal and infant outcomes, such as those important outcomes pre-specified in this review. As only a proportion of women will be diagnosed with GDM in these trials, large sample sizes may be required.
-
6.
Celiac Disease in Women With Infertility: A Meta-Analysis.
Singh, P, Arora, S, Lal, S, Strand, TA, Makharia, GK
Journal of clinical gastroenterology. 2016;(1):33-9
Abstract
BACKGROUND Celiac disease (CeD) is a systemic disease with manifestations not limited to small intestine. The data on association between CeD and infertility is contradictory. There are no recommendations for the screening of female patients with infertility for CeD. AIM: We conducted a meta-analysis to find out whether women with infertility are at higher risk of CeD. METHODS Literature search was performed using the MeSH keywords "CeD," "gluten," and "infertility." Diagnosis of CeD was based on positive serology and biopsies showing villous atrophy. Data were extracted about CeD patients in 3 groups-women with infertility (including unexplained infertility), unexplained infertility, and controls. Pooled odds ratio (OR) and prevalence, with 95% confidence intervals (CI), were calculated. RESULTS Of 105 relevant studies, 5 studies were included for calculation of pooled OR. Four additional studies, where data on controls were not available, were also considered for calculation of pooled prevalence of CeD. Women with infertility had 3.5 times higher odds of having CeD in comparison with control population (OR=3.5; 95% CI, 1.3-9; P<0.01). Similarly, women with "unexplained infertility" had 6 times higher odds of having CeD than controls (OR=6; 95% CI, 2.4-14.6). Of 884 women with infertility, 20 had CeD indicating a pooled prevalence of 2.3% (95% CI, 1.4-3.5). Of 623 women with "unexplained infertility," 20 had CeD. The pooled prevalence of CeD in women with unexplained infertility was 3.2 (95% CI, 2-4.9). CONCLUSIONS CeD is more prevalent in women with "all-cause" infertility and "unexplained" infertility than that in general population.
-
7.
The identification and treatment of women with hyperglycaemia in pregnancy: an analysis of individual participant data, systematic reviews, meta-analyses and an economic evaluation.
Farrar, D, Simmonds, M, Griffin, S, Duarte, A, Lawlor, DA, Sculpher, M, Fairley, L, Golder, S, Tuffnell, D, Bland, M, et al
Health technology assessment (Winchester, England). 2016;(86):1-348
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is associated with a higher risk of important adverse outcomes. Practice varies and the best strategy for identifying and treating GDM is unclear. AIM: To estimate the clinical effectiveness and cost-effectiveness of strategies for identifying and treating women with GDM. METHODS We analysed individual participant data (IPD) from birth cohorts and conducted systematic reviews to estimate the association of maternal glucose levels with adverse perinatal outcomes; GDM prevalence; maternal characteristics/risk factors for GDM; and the effectiveness and costs of treatments. The cost-effectiveness of various strategies was estimated using a decision tree model, along with a value of information analysis to assess where future research might be worthwhile. Detailed systematic searches of MEDLINE® and MEDLINE In-Process & Other Non-Indexed Citations®, EMBASE, Cumulative Index to Nursing and Allied Health Literature Plus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database, Maternity and Infant Care database and the Cochrane Methodology Register were undertaken from inception up to October 2014. RESULTS We identified 58 studies examining maternal glucose levels and outcome associations. Analyses using IPD alone and the systematic review demonstrated continuous linear associations of fasting and post-load glucose levels with adverse perinatal outcomes, with no clear threshold below which there is no increased risk. Using IPD, we estimated glucose thresholds to identify infants at high risk of being born large for gestational age or with high adiposity; for South Asian (SA) women these thresholds were fasting and post-load glucose levels of 5.2 mmol/l and 7.2 mmol/l, respectively and for white British (WB) women they were 5.4 and 7.5 mmol/l, respectively. Prevalence using IPD and published data varied from 1.2% to 24.2% (depending on criteria and population) and was consistently two to three times higher in SA women than in WB women. Lowering thresholds to identify GDM, particularly in women of SA origin, identifies more women at risk, but increases costs. Maternal characteristics did not accurately identify women with GDM; there was limited evidence that in some populations risk factors may be useful for identifying low-risk women. Dietary modification additional to routine care reduced the risk of most adverse perinatal outcomes. Metformin (Glucophage,® Teva UK Ltd, Eastbourne, UK) and insulin were more effective than glibenclamide (Aurobindo Pharma - Milpharm Ltd, South Ruislip, Middlesex, UK). For all strategies to identify and treat GDM, the costs exceeded the health benefits. A policy of no screening/testing or treatment offered the maximum expected net monetary benefit (NMB) of £1184 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY). The NMB for the three best-performing strategies in each category (screen only, then treat; screen, test, then treat; and test all, then treat) ranged between -£1197 and -£1210. Further research to reduce uncertainty around potential longer-term benefits for the mothers and offspring, find ways of improving the accuracy of identifying women with GDM, and reduce costs of identification and treatment would be worthwhile. LIMITATIONS We did not have access to IPD from populations in the UK outside of England. Few observational studies reported longer-term associations, and treatment trials have generally reported only perinatal outcomes. CONCLUSIONS Using the national standard cost-effectiveness threshold of £20,000 per QALY it is not cost-effective to routinely identify pregnant women for treatment of hyperglycaemia. Further research to provide evidence on longer-term outcomes, and more cost-effective ways to detect and treat GDM, would be valuable. STUDY REGISTRATION This study is registered as PROSPERO CRD42013004608. FUNDING The National Institute for Health Research Health Technology Assessment programme.
-
8.
Screening Strategies and Primary Prevention Interventions in Relatives of People With Coronary Artery Disease: A Systematic Review and Meta-analysis.
Goldfarb, M, Slobod, D, Dufresne, L, Brophy, JM, Sniderman, A, Thanassoulis, G
The Canadian journal of cardiology. 2015;(5):649-57
Abstract
BACKGROUND Relatives of people with coronary artery disease are at high risk of cardiovascular (CV) disease, but the effect of focused screening and treatment of this population is uncertain. METHODS We searched the Cochrane Library, Medline, and Embase from inception until June 30, 2014 for articles that described screening strategies and primary prevention interventions targeting family members of patients with coronary artery disease to reduce CV risk. Results were pooled using a random-effects meta-analysis. RESULTS We identified 18 studies that reported screening strategies and 15 reporting interventions to reduce CV risk. Proband willingness to refer relatives for screening was high (n = 6 studies, pooled rate = 87%; 95% confidence interval [CI], 80%-95%). Studies using a screening strategy in which the relative was contacted by health care professionals reported a pooled participation rate of 88% (95% CI, 78%-99%). The quality of interventional studies was highly variable. Random-effects meta-analysis of the highest quality randomized studies (n = 6) consisting of a specialized risk factor intervention compared with usual care was consistent with modest improvements in low-density lipoprotein cholesterol control (-0.18 mmol/L low-density lipoprotein cholesterol, 95% CI, -0.35 to -0.001; P = 0.048). Improvements in diet, smoking rates, exercise, and blood pressure were also observed with active intervention; however, reported outcomes were heterogeneous precluding a formal meta-analysis. CONCLUSIONS Screening strategies that target family members, particularly when led by a health care professional, achieve a high participation rate. Although the available evidence is of variable quality, interventions that target individuals with a family history of coronary artery disease appear to be feasible and might be effective in improving certain risk factors or health behaviours but their long-term CV benefits remain uncertain.
-
9.
Use of high-normal levels of haemoglobin A(1C) and fasting plasma glucose for diabetes screening and for prediction: a meta-analysis.
Kodama, S, Horikawa, C, Fujihara, K, Hirasawa, R, Yachi, Y, Yoshizawa, S, Tanaka, S, Sone, Y, Shimano, H, Iida, KT, et al
Diabetes/metabolism research and reviews. 2013;(8):680-92
Abstract
BACKGROUND Using high-normal levels of haemoglobin A1C (Abnormal-A1C ) or fasting plasma glucose (FPG) (Abnormal-FPG) for diabetes screening are expected to improve the ability to detect persons with or at high risk of diabetes. We assessed the diagnostic and predictive capacity for diabetes of Abnormal-A1C and Abnormal-FPG. We compared these to the combined use of the two measures to the single use of either measurement. METHODS We analysed 31 eligible cross-sectional or cohort studies that assessed diagnostic or predictive ability, respectively, by using lower A1C and FPG cutoff values than recommended by current diabetes criteria. Positive and negative likelihood ratios (LR+ and LR-) were calculated to assess the ability to confirm or exclude diabetes, respectively, on the basis of a bivariate random-effects model. RESULTS With both Abnormal-A1C and Abnormal-FPG, the pooled LR+ was above 4 for diagnosing diabetes and above 3 for predicting diabetes. However, the pooled LR- for predicting diabetes was higher with Abnormal-A1C (0.48) and Abnormal-FPG (0.49) in comparison with that for diagnosing diabetes (0.27, Abnormal-A1C ; 0.28, Abnormal-FPG). In eight studies that assessed the predictive ability of the combination of A1C and FPG, using either Abnormal-A1C or Abnormal-FPG could lower LR- to 0.17 from 0.43 for only Abnormal-A1C and from 0.38 for only Abnormal-FPG. Accordingly, LR+ was also lowered to 2.37 from 3.36 for only Abnormal-A1C and from 3.84 for only-Abnormal-FPG. CONCLUSION The use of the two blood glucose tests had insufficient capacity to identify subjects at high risk for diabetes but had considerable capacity to identify undiagnosed diabetes.
-
10.
General health checks in adults for reducing morbidity and mortality from disease.
Krogsbøll, LT, Jørgensen, KJ, Grønhøj Larsen, C, Gøtzsche, PC
The Cochrane database of systematic reviews. 2012;:CD009009
Abstract
BACKGROUND General health checks are common elements of health care in some countries. These aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is, therefore, important to assess whether general health checks do more good than harm. OBJECTIVES We aimed to quantify the benefits and harms of general health checks with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes such as blood pressure and serum cholesterol levels. SEARCH METHODS We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register, MEDLINE, EMBASE, Healthstar, CINAHL, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) to July 2012. Two authors screened titles and abstracts, assessed papers for eligibility and read reference lists. One author used citation tracking (Web of Knowledge) and asked trialists about additional studies. SELECTION CRITERIA We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening general populations for more than one disease or risk factor in more than one organ system. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed the risk of bias in the trials. We contacted authors for additional outcomes or trial details when necessary. For mortality outcomes we analysed the results with random-effects model meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. MAIN RESULTS We included 16 trials, 14 of which had available outcome data (182,880 participants). Nine trials provided data on total mortality (155,899 participants, 11,940 deaths), median follow-up time nine years, giving a risk ratio of 0.99 (95% confidence interval (CI) 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (152,435 participants, 4567 deaths), risk ratio 1.03 (95% CI 0.91 to 1.17) and eight trials on cancer mortality (139,290 participants, 3663 deaths), risk ratio 1.01 (95% CI 0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings.We did not find an effect on clinical events or other measures of morbidity but one trial found an increased occurrence of hypertension and hypercholesterolaemia with screening and one trial found an increased occurence of self-reported chronic disease. One trial found a 20% increase in the total number of new diagnoses per participant over six years compared to the control group. No trials compared the total number of prescriptions, but two out of four trials found an increased number of people using antihypertensive drugs. Two out of four trials found small beneficial effects on self-reported health, but this could be due to reporting bias as the trials were not blinded. We did not find an effect on admission to hospital, disability, worry, additional visits to the physician, or absence from work, but most of these outcomes were poorly studied. We did not find useful results on the number of referrals to specialists, the number of follow-up tests after positive screening results, or the amount of surgery. AUTHORS' CONCLUSIONS General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although the number of new diagnoses was increased. Important harmful outcomes, such as the number of follow-up diagnostic procedures or short term psychological effects, were often not studied or reported and many trials had methodological problems. With the large number of participants and deaths included, the long follow-up periods used, and considering that cardiovascular and cancer mortality were not reduced, general health checks are unlikely to be beneficial.