Measuring and exploring mental health determinants: a closer look at co-residents' effect using a multilevel structural equations model.

OBJECTIVE: Previous research has demonstrated that individual risk of mental illness is associated with individual, co-resident, and household risk factors. However, modelling the overall effect of these risk factors presents several methodological challenges. In this study we apply a multilevel structural equation model (MSEM) to address some of these challenges and the impact of the different determinants when measuring mental health risk. STUDY DESIGN AND SETTING: Two thousand, one hundred forty-three individuals aged 16 and over from 888 households were analysed based on the Household Survey for England-2014 dataset. We applied MSEM to simultaneously measure and identify psychiatric morbidity determinants while accounting for the dependency among individuals within the same household and the measurement errors. RESULTS: Younger age, female gender, non-working status, headship of the household, having no close relationship with other people, having history of mental illness and obesity were all significant (p < 0.01) individual risk factors for psychiatric morbidity. A previous history of mental illness in the co-residents, living in a deprived household, and a lack of closeness in relationships among residents were also significant predictors. Model fit indices showed a very good model specification (CFI = 0.987, TLI = 0.980, RMSEA = 0.023, GFI = 0.992). CONCLUSION: Measuring and addressing mental health determinants should consider not only an individual's characteristics but also the co-residents and the households in which they live.

Comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study using routine data of faecal calprotectin testing for inflammatory bowel disease.

BACKGROUND: Meta-analyses of test accuracy studies may provide estimates that are highly improbable in clinical practice. Tailored meta-analysis produces plausible estimates for the accuracy of a test within a specific setting by tailoring the selection of included studies compatible with a specific setting using information from the target setting. The aim of this study was to validate the tailored meta-analysis approach by comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study. METHODS: A retrospective cohort study of primary care electronic health records provided setting-specific data on the test positive rate and disease prevalence. This was used to tailor the study selection from a review of faecal calprotectin testing for inflammatory bowel disease for meta-analysis using the binomial method and the Mahalanobis distance method. Tailored estimates were compared to estimates from a study of test accuracy in primary care using the same routine dataset. RESULTS: Tailoring resulted in the inclusion of 3/14 (binomial method) and 9/14 (Mahalanobis distance method) studies in meta-analysis. Sensitivity and specificity from tailored meta-analysis using the binomial method were 0.87 (95% CI 0.77 to 0.94) and 0.65 (95% CI 0.60 to 0.69) and 0.98 (95% CI 0.83 to 0.999) and 0.68 (95% CI 0.65 to 0.71), respectively using the Mahalanobis distance method. The corresponding estimates for the conventional meta-analysis were 0.94 (95% CI 0.90 to 0.97) and 0.67 (95% CI 0.57 to 0.76) and for the FC test accuracy study of primary care data 0.93 (95%CI 0.89 to 0.96) and 0.61 (95% CI 0.6 to 0.63) to detect IBD at a threshold of 50 µg/g. Although the binomial method produced a plausible estimate, the tailored estimates of sensitivity and specificity were not closer to the primary study estimates than the estimates from conventional meta-analysis including all 14 studies. CONCLUSIONS: Tailored meta-analysis does not always produce estimates of sensitivity and specificity that lie closer to the estimates derived from a primary study in the setting in question. Potentially, tailored meta-analysis may be improved using a constrained model approach and this requires further investigation.

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.

BACKGROUND: Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown. OBJECTIVES: We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section. DESIGN: This was a controlled interrupted time series study. SETTING: The study took place in primary and secondary care. PARTICIPANTS: Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally. INTERVENTIONS: In-utero exposure to antibiotics immediately prior to birth. MAIN OUTCOME MEASURES: Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed. DATA SOURCES: The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set. RESULTS: In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively. LIMITATIONS: It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years. CONCLUSIONS: There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK. FUTURE WORK: There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children. STUDY REGISTRATION: This study is registered as researchregistry3736. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Women giving birth by caesarean section are at risk of developing infections (such as wound infections) and are offered antibiotics at the time of their operation to reduce this risk. In 2011, the national guidelines changed from recommending antibiotics after cord clamping to giving them before the operation to further reduce the risk of maternal infection. During birth, the newborn gut is colonised by microbes. Antibiotics given to the mother before caesarean section can reach the baby through the placenta and disrupt the normal microbes that colonise the gut. These microbes are believed to play a role in the development of the immune system and altering the normal development of these microbes has been linked to children developing allergic conditions, such as asthma and eczema. This study investigated whether or not giving antibiotics before the caesarean section had a longer-term impact on children's health. WHAT DID WE DO?: We used routine NHS information already collected by hospitals and general practitioners about women who gave birth in the UK between 2006 and 2018, and their children. We compared the risk of asthma, eczema and other health conditions in the first 5 years after birth in children born by caesarean section before and after the change in hospital policies. We also compared their health with children born vaginally. WHAT DID WE FIND?: We found that there was no increased risk of asthma or eczema for children born by caesarean section after the policy decision in 2011 to give the mother antibiotics before the operation. WHAT DOES THIS MEAN?: The study findings provide further evidence for the current recommendation to give preventative antibiotics to women shortly before the caesarean section to reduce the overall risk of infections after birth.

Risk of developing gallbladder cancer in patients with gallbladder polyps detected on transabdominal ultrasound: a systematic review and meta-analysis.

OBJECTIVE: To estimate the risk of malignancy in gallbladder polyps of incremental sizes detected during transabdominal ultrasound (TAUS). METHODS: We searched databases including MEDLINE, Embase, and Cochrane Library for eligible studies recording the polyp size from which gallbladder malignancy developed, confirmed following cholecystectomy, or by subsequent follow-up. Primary outcome was the risk of gallbladder cancer in patients with polyps. Secondary outcome was the effect of polyp size as a prognostic factor for cancer. Risk of bias was assessed using the Quality in Prognostic Factor Studies (QUIPS) tool. Bayesian meta-analysis estimated the median cancer risk according to polyp size. This study is registered with PROSPERO (CRD42020223629). RESULTS: 82 studies published since 1990 reported primary data for 67,837 patients. 67,774 gallbladder polyps and 889 cancers were reported. The cumulative median cancer risk of a polyp measuring 10 mm or less was 0.60% (99% credible range 0.30-1.16%). Substantial heterogeneity existed between studies (I2 = 99.95%, 95% credible interval 99.86-99.98%). Risk of bias was generally high and overall confidence in evidence was low. 13 studies (15.6%) were graded with very low certainty, 56 studies (68.3%) with low certainty, and 13 studies (15.6%) with moderate certainty. In studies considered moderate quality, TAUS monitoring detected 4.6 cancers per 10,000 patients with polyps less than 10 mm. CONCLUSION: Malignant risk in gallbladder polyps is low, particularly in polyps less than 10 mm, however the data are heterogenous and generally low quality. International guidelines, which have not previously modelled size data, should be informed by these findings. ADVANCES IN KNOWLEDGE: This large systematic review and meta-analysis has shown that the mean cumulative risk of small gallbladder polyps is low, but heterogeneity and missing data in larger polyp sizes (>10 mm) means the risk is uncertain and may be higher than estimated.Studies considered to have better methodological quality suggest that previous estimates of risk are likely to be inflated.

Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records.

OBJECTIVE: To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping. DESIGN: Observational controlled interrupted time series study. SETTING: UK primary and secondary care. PARTICIPANTS: 515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping. INTERVENTION: Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure. MAIN OUTCOME MEASURES: The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally. RESULTS: Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years. CONCLUSIONS: This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.

Clustering functional data using forward search based on functional spatial ranks with medical applications.

Cluster analysis of functional data is finding increasing application in the field of medical research and statistics. Here we introduce a functional version of the forward search methodology for the purpose of functional data clustering. The proposed forward search algorithm is based on the functional spatial ranks and is a data-driven non-parametric method. It does not require any preprocessing functional data steps, nor does it require any dimension reduction before clustering. The Forward Search Based on Functional Spatial Rank (FSFSR) algorithm identifies the number of clusters in the curves and provides the basis for the accurate assignment of each curve to its cluster. We apply it to three simulated datasets and two real medical datasets, and compare it with six other standard methods. Based on both simulated and real data, the FSFSR algorithm identifies the correct number of clusters. Furthermore, when compared with six standard methods used for clustering and classification, it records the lowest misclassification rate. We conclude that the FSFSR algorithm has the potential to cluster and classify functional data.

Faecal calprotectin testing in UK general practice: a retrospective cohort study using The Health Improvement Network database.

BACKGROUND: Faecal calprotectin (FC) testing to detect inflammatory bowel disease (IBD) was recommended for use in UK general practice in 2013. The actual use of FC testing following the national recommendations is unknown. AIM: To characterise the use of FC testing for IBD in UK general practice. DESIGN AND SETTING: A retrospective cohort study of routine electronic patient records from The Health Improvement Network database from UK general practice. METHOD: The study included 6 965 853 adult patients (aged ≥18 years), between 2006 and 2016. FC test uptake, the patients tested, and patient management following testing were characterised. RESULTS: A total of 17 027 patients had 19 840 FC tests recorded. The mean age of tested patients was 44.2 years. The first FC tests were documented in 2009. FC test use was still increasing in 2016. By 2016, 66.8% (n = 493/738) of practices had started FC testing. About one-fifth (20.7%, n = 1253/6051) of tests were carried out in patients aged ≥60 years. Only 7.8% (n = 473/6051) of the FC test records were preceded by symptoms eligible for FC testing. Only 3.1% (n = 1720/55 477) of patients with eligible symptoms have received FC testing since the national recommendations were published. There was only a small number of patients with symptoms, FC test, and a IBD diagnosis. In total, 71.3% (n = 1416/1987) of patients with a positive and 47.7% (n = 1337/2805) with a negative FC test were referred or further investigated. CONCLUSION: Uptake of FC testing in clinical practice has been slow and inconsistent. The indication of non-compliance with national recommendations may suggest that these recommendations lack applicability to the general practice context.

The incidence and prevalence of inflammatory bowel disease in UK primary care: a retrospective cohort study of the IQVIA Medical Research Database.

BACKGROUND: Our knowledge of the incidence and prevalence of inflammatory bowel disease (IBD) is uncertain. Recent studies reported an increase in prevalence. However, they excluded a high proportion of ambiguous cases from general practice. Estimates are needed to inform health care providers who plan the provision of services for IBD patients. We aimed to estimate the IBD incidence and prevalence in UK general practice. METHODS: We undertook a retrospective cohort study of routine electronic health records from the IQVIA Medical Research Database covering 14 million patients. Adult patients from 2006 to 2016 were included. IBD was defined as an IBD related Read code or record of IBD specific medication. Annual incidence and 12-month period prevalence were calculated. RESULTS: The prevalence of IBD increased between 2006 and 2016 from 106.2 (95% CI 105.2-107.3) to 142.1 (95% CI 140.7-143.5) IBD cases per 10,000 patients which is a 33.8% increase. Incidence varied across the years. The incidence across the full study period was 69.5 (95% CI 68.6-70.4) per 100,000 person years. CONCLUSIONS: In this large study we found higher estimates of IBD incidence and prevalence than previously reported. Estimates are highly dependent on definitions of disease and previously may have been underestimated.

Test accuracy of faecal calprotectin for inflammatory bowel disease in UK primary care: a retrospective cohort study of the IMRD-UK data.

OBJECTIVE: To estimate the test accuracy of faecal calprotectin (FC) for inflammatory bowel disease (IBD) in the primary care setting using routine electronic health records. DESIGN: Retrospective cohort test accuracy study. SETTING: UK primary care. PARTICIPANTS: 5970 patients (≥18 years) without a previous IBD diagnosis and with a first FC test between 1 January 2006 and 31 December 2016. We excluded multiple tests and tests without numeric results in units of µg/g. INTERVENTION: FC testing for the diagnosis of IBD. Disease status was confirmed by a recorded diagnostic code and/or a drug code of an IBD-specific medication at three time points after the FC test date. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values for the differential of IBD versus non-IBD and IBD versus irritable bowel syndrome (IBS) at the 50 and 100 µg/g thresholds. RESULTS: 5970 patients met the inclusion criteria and had at least 6 months of follow-up data after FC testing. 1897 had an IBS diagnosis, 208 had an IBD diagnosis, 31 had a colorectal cancer diagnosis, 80 had more than one diagnosis and 3754 had no subsequent diagnosis. Sensitivity, specificity, and positive and negative predictive values were 92.9% (88.6% to 95.6%), 61.5% (60.2% to 62.7%), 8.1% (7.1% to 9.2%) and 99.6% (99.3% to 99.7%), respectively, at the threshold of 50 µg/g. Raising the threshold to 100 µg/g missed less than 7% additional IBD cases. Longer follow-up had no effect on test accuracy. Overall, uncertainty was greater for specificity than sensitivity. General practitioners' (GPs') referral decisions did not follow the anticipated clinical pathways in national guidance. CONCLUSIONS: GPs can be confident in excluding IBD on the basis of a negative FC test in a population with low pretest risk but should interpret a positive test with caution. The applicability of national guidance to general practice needs to be improved.

Factors predicting statin prescribing for primary prevention: a historical cohort study.

BACKGROUND: Initiation of statins for the primary prevention of cardiovascular disease (CVD) should be based on CVD risk estimates, but their use is suboptimal. AIM: To investigate the factors influencing statin prescribing when clinicians code and do not code estimated CVD risk (QRISK2). DESIGN AND SETTING: A historical cohort of patients who had lipid tests in a database (IQVIA Medical Research Data) of UK primary care records. METHOD: The cohort comprised 686 560 entries (lipid test results) between 2012 and 2016 from 383 416 statin-naive patients without previous CVD. Coded QRISK2 scores were extracted, with variables used in calculating QRISK2 and factors that might influence statin prescribing. If a QRISK2 score was not coded, it was calculated post hoc. The outcome was initiation of a statin within 60 days of the lipid test result. RESULTS: Of the entries, 146 693 (21.4%) had a coded QRISK2 score. Statins were initiated in 6.6% (95% confidence interval [CI] = 6.4% to 6.7%) of those with coded and 4.1% (95% CI = 4.0% to 4.1%) of uncoded QRISK2 (P<0.001). Statin initiations were consistent with National Institute for Health and Care Excellence guideline recommendations in 85.0% (95% CI = 84.2% to 85.8%) of coded and 44.2% (95% CI = 43.5% to 44.9%) of uncoded QRISK2 groups (P<0.001). When coded, QRISK2 score was the main predictor of statin initiation, but total cholesterol was the main predictor when a QRISK2 score was not coded. CONCLUSION: When a QRISK2 score is coded, prescribing is more consistent with guidelines. With no QRISK2 score, prescribing is mainly based on total cholesterol. Using QRISK2 is associated with statin prescribing that is more likely to benefit patients. Promoting the routine CVD risk estimation is essential to optimise decision making.

Comparison of Centor and McIsaac scores in primary care: a meta-analysis over multiple thresholds.

BACKGROUND: Centor and McIsaac scores are both used to diagnose group A beta-haemolytic streptococcus (GABHS) infection, but have not been compared through meta-analysis. AIM: To compare the performance of Centor and McIsaac scores at diagnosing patients with GABHS presenting to primary care with pharyngitis. DESIGN AND SETTING: A meta-analysis of diagnostic test accuracy studies conducted in primary care was performed using a novel model that incorporates data at multiple thresholds. METHOD: MEDLINE, EMBASE, and PsycINFO were searched for studies published between January 1980 and February 2019. Included studies were: cross-sectional; recruited patients with sore throats from primary care; used the Centor or McIsaac score; had GABHS infection as the target diagnosis; used throat swab culture as the reference standard; and reported 2 × 2 tables across multiple thresholds. Selection and data extraction were conducted by two independent reviewers. QUADAS-2 was used to assess study quality. Summary receiver operating characteristic (SROC) curves were synthesised. Calibration curves were used to assess the transferability of results into practice. RESULTS: Ten studies using the Centor score and eight using the McIsaac score were included. The prevalence of GABHS ranged between 4% and 44%. The areas under the SROC curves for McIsaac and Centor scores were 0.7052 and 0.6888, respectively. The P-value for the difference (0.0164) was 0.419, suggesting the SROC curves for the tests are equivalent. Both scores demonstrated poor calibration. CONCLUSION: Both Centor and McIsaac scores provide only fair discrimination of those with and without GABHS, and appear broadly equivalent in performance. The poor calibration for a positive test result suggests other point-of-care tests are required to rule in GABHS; however, with both Centor and McIsaac scores, a score of ≤0 may be sufficient to rule out infection.

Maximum likelihood estimation based on Newton-Raphson iteration for the bivariate random effects model in test accuracy meta-analysis.

A bivariate generalised linear mixed model is often used for meta-analysis of test accuracy studies. The model is complex and requires five parameters to be estimated. As there is no closed form for the likelihood function for the model, maximum likelihood estimates for the parameters have to be obtained numerically. Although generic functions have emerged which may estimate the parameters in these models, they remain opaque to many. From first principles we demonstrate how the maximum likelihood estimates for the parameters may be obtained using two methods based on Newton-Raphson iteration. The first uses the profile likelihood and the second uses the Observed Fisher Information. As convergence may depend on the proximity of the initial estimates to the global maximum, each algorithm includes a method for obtaining robust initial estimates. A simulation study was used to evaluate the algorithms and compare their performance with the generic generalised linear mixed model function glmer from the lme4 package in R before applying them to two meta-analyses from the literature. In general, the two algorithms had higher convergence rates and coverage probabilities than glmer. Based on its performance characteristics the method of profiling is recommended for fitting the bivariate generalised linear mixed model for meta-analysis.

Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records.

INTRODUCTION: In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health. METHODS AND ANALYSIS: A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.

Faecal calprotectin to detect inflammatory bowel disease: a systematic review and exploratory meta-analysis of test accuracy.

OBJECTIVE: Test accuracy of faecal calprotectin (FC) testing in primary care is inconclusive. We aimed to assess the test accuracy of FC testing in primary care and compare it to secondary care estimates for the detection of inflammatory bowel disease (IBD). METHODS: Systematic review and meta-analysis of test accuracy using a bivariate random effects model. We searched MEDLINE, EMBASE, Cochrane Library and Web of Science until 31 May 2017 and included studies from auto alerts up until 31 January 2018. Eligible studies measured FC levels in stool samples to detect IBD in adult patients with chronic (at least 6-8 weeks) abdominal symptoms in primary or secondary care. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We followed the protocol registered as PROSPERO CRD 42012003287. RESULTS: 38 out of 2168 studies were eligible including five from primary care. Comparison of test accuracy by setting was precluded by extensive heterogeneity. Overall, summary estimates of sensitivity and specificity were not recorded. At a threshold of 50 µg/g, sensitivity from separate meta-analysis of four assay types ranged from 0.85 (95% CI 0.75 to 0.92) to 0.94 (95% CI 0.75 to 0.90) and specificity from 0.67 (95% CI 0.56 to 0.76) to 0.88 (95% CI 0.77 to 0.94). Across three different definitions of disease, sensitivity ranged from 0.80 (95% CI 0.76 to 0.84) to 0.97 (95% CI 0.91 to 0.99) and specificity from 0.67 (95% CI 0.58 to 0.75) to 0.76 (95% CI 0.66 to 0.84). Sensitivity appears to be lower in primary care and is further reduced at a revised threshold of 100 µg/g. CONCLUSIONS: Conclusive estimates of sensitivity and specificity of FC testing in primary care for the detection of IBD are still missing. There is insufficient evidence in the published literature to support the decision to introduce FC testing in primary care. Studies evaluating FC testing in an appropriate primary care setting are needed.

Cancer as a risk factor for urinary tract calculi: a retrospective cohort study using 'The Health Improvement Network' : Cancer and urinary tract calculi.

PURPOSE: Urolithiasis is a common condition that poses significant morbidity to patients. There are similarities in the development of certain cancers and urinary tract calculi (UTC), however, little is known about their temporal relationship. This study aims to identify if cancer is a risk factor for the development of UTC. METHODS: A population-based retrospective cohort study was conducted for the period 1st January 1990 to 1st May 2016. 124,901 exposed patients identified using clinical codes with newly diagnosed cancer were matched to 476,203 unexposed controls by age, gender, BMI, and general practice. The main outcome measure was the risk of developing UTC described by hazard ratios. RESULTS: There were 512 incident UTC events in the cancer group compared to 1787 in the unexposed controls. This translated to an adjusted hazard ratio of 1.26 (95% CI 1.14-1.39; p < 0.001). A sub-analysis assessing cancer-specific effects demonstrated increased risks for 10 out of 12 common cancers, most significantly in bladder, colorectal and prostate cancer. CONCLUSION: This study demonstrated a 26% increased risk of UTC in cancer patients suggesting wider recognition of this risk amongst clinicians could improve diagnosis and prevention of UTC, as well as encourage further research exploring this association.

Tailored meta-analysis: an investigation of the correlation between the test positive rate and prevalence.

BACKGROUND AND OBJECTIVE: Meta-analysis may produce estimates that are unrepresentative of a test's performance in practice. Tailored meta-analysis (TMA) circumvents this by deriving an applicable region for the practice and selecting the studies compatible with the region. It requires the test positive rate, r and prevalence, p being estimated for the setting but previous studies have assumed their independence. The aim is to investigate the effects a correlation between r and p has on estimating the applicable region and how this affects TMA. METHODS: Six methods for estimating 99% confidence intervals (CI) for r and p were investigated: Wilson's ± Bonferroni correction, Clopper-Pearson's ± Bonferroni correction, and Hotelling's T2 statistic ± continuity correction. These were analyzed in terms of the coverage probability using simulation trials over different correlations, sample sizes, and values for r and p. The methods were then applied to two published meta-analyses with associated practice data, and the effects on the applicable region, studies selected, and summary estimates were evaluated. RESULTS: Hotelling's T2 statistic with a continuity correction had the highest median coverage (0.9971). This and the Clopper-Pearson method with a Bonferroni correction both had coverage consistently above 0.99. The coverage of Hotelling's CI's varied the least across different correlations. For both meta-analyses, the number of studies selected was largest when Hotelling's T2 statistic was used to derive the applicable region. In one instance, this increased the sensitivity by over 4% compared with TMA estimates using other methods. CONCLUSION: TMA returns estimates that are tailored to practice providing the applicable region is accurately defined. This is most likely when the CI for r and p are estimated using Hotelling's T2 statistic with a continuity correction. Potentially, the applicable region may be obtained using routine electronic health data.

Visual and radiographic caries detection: a tailored meta-analysis for two different settings, Egypt and Germany.

BACKGROUND: Diagnostic meta-analyses on caries detection methods should assist practitioners in their daily practice. However, conventional meta-analysis estimates may be inapplicable due to differences in test conduct, applied thresholds and assessed population between settings. Our aim was to demonstrate the impact of tailored meta-analysis of visual and radiographic caries detection to different settings using setting-specific routine data. METHODS: Published systematic reviews and meta-analyses on the accuracy of visual and radiographic caries detection were used. In two settings (a private practice in Germany and a public health clinic in Egypt), routine data of a total of 100 (n = 50/practice) consecutive 12-14 year-olds were collected. Test-positive rates of visual and radiographic detection for initial and advanced carious lesions on occlusal or proximal surfaces of molars were used to tailor meta-analyses. If prevalence data were available, these were also used for tailoring. RESULTS: From the original reviews, 210 and 100 heterogeneous studies on visual and radiographic caries detection were included in our meta-analyses. For radiographic detection, sensitivity and specificity estimates derived from conventional and tailored meta-analysis were similar. For visual detection of advanced occlusal carious lesions, the conventional meta-analysis yielded a sensitivity and specificity (95% CI) of 64.6% (57-71) and 90.9% (88-93), whereas the tailored estimates for Egypt were 75.1% (70-81) and 84.9% (82-89), respectively, and 43.7% (37-51) and 96.5% (95-97) for Germany, respectively. CONCLUSION: Conventional test accuracy meta-analyses may yield aggregate estimates which are inapplicable to specific settings. Routine data may be used to produce a meta-analysis estimate which is tailored to the setting and thereby improving its applicability.