Colorectal cancer testing rates after implementation of an organised screening programme in Vaud, Switzerland.

AIMS OF THE STUDY: Canton Vaud, Switzerland, implemented an organised colorectal cancer  screening programme with colonoscopy and faecal occult blood tests in 2015, 4 to 6 years ahead of neighbouring cantons. Before its implementation, nearly half of Swiss citizens were already up to date with screening, primarily from opportunistic colonoscopies. We hypothesised that earlier implementation of an organised programme would be associated with greater increases in colorectal cancer testing rates. METHODS: We analysed Swiss health insurance claim data from CSS, a Swiss health insurer covering 16% of the Swiss population and 10% of canton Vaud. We stratified 50-69-year-olds into groups from Vaud, its four neighbouring cantons (Fribourg, Geneva, Neuchâtel and Valais), and the rest of Switzerland. We analysed overall, faecal occult blood test and colonoscopy testing rates for each year between 2010 and 2018. RESULTS: The overall testing rate increased from 7.6% in 2010 to 11.6% in 2018 (+4.0%) in Vaud, from 6.1% to 9.3% (+3.2%) in neighbouring cantons and from 7.4% to 8.6% (+1.2%) in the rest of Switzerland. The faecal occult blood test rate increased between 2016 and 2018 from 2.9% to 4.1% (+1.2%) in Vaud and from 1.7% to 2.6% (+0.9%) in neighbouring cantons, but it decreased from 3.1% to 1.5% (-1.6%) in the rest of Switzerland. The colonoscopy rate increased in all cantons, from 4.7% to 7.5% in Vaud (+2.8%), from 4.4% to 6.7% in neighbouring cantons (+2.3%) and from 4.3% to 7.1% in the rest of Switzerland (+2.8%). By 2018, 40% of faecal occult blood tests and 26% of colonoscopies in Vaud occurred in the organised programme. Those who completed an faecal occult blood test within the Vaud programme were younger, had fewer comorbidities and were more likely to have a high-deductible health plan than those tested outside the programme. CONCLUSIONS: Colorectal cancer testing rates increased between 2010 and 2018, with greater absolute increases in Vaud than in neighbouring cantons or the rest of Switzerland. Faecal occult blood test use increased in both Vaud and neighbouring cantons, possibly reflecting changes in testing patterns by general practitioners. By 2018, 40% of colonoscopies and 26% of faecal occult blood tests occurred within the screening programme.

Change in colorectal cancer (CRC) testing rates associated with the introduction of the first organized screening program in canton Uri, Switzerland: Evidence from insurance claims data analyses from 2010 to 2018.

The first canton in Switzerland to implement an organized colorectal cancer screening program (OSP) was Uri. Starting in 2013, it offered 50-69-year-olds free testing with colonoscopy every 10 years or fecal occult blood test (FOBT) every 2 years. We tested the association between the OSP and testing rates over time. We analyzed claims data of 50-69-year-olds from Uri and neighboring cantons (NB) provided by a large health insurance and complemented it with data from the OSP. We fitted multivariate adjusted logistic regression models to compare overall testing rates and by method (colonoscopy or FOBT/both) We computed the 2018 rate of the population up-to-date with testing (colonoscopy within 9 years/FOBT within 2 years). Yearly overall testing rates in Uri increased from 8.7% in 2010 to 10.8% in 2018 and from 6.5% to 7.9% in NB. In Uri, the proportion tested with FOBT/both increased from 4.7% to 6.0% but decreased from 2.8% to 1.1% in NB. Testing by FOBT/both increased more between 2015 and 2018 than 2010-2012 in Uri than in NB (OR:2.1[95%CI:1.8-2.4]), it increased less for colonoscopy (OR:0.60[95%CI:0.51-0.70]), with no change in overall CRC testing (OR:0.91[95%CI:0.81-1.02]). In 2018 in Uri, 42.5% were up-to-date with testing (FOBT/both:9.2%, colonoscopy:35.7%); in NBs, 40.7% (FOBT/both:2.7%, colonoscopy:39%). Yearly FOBT rates in Uri were always higher than in NB. Though the OSP in Uri was not associated with a greater increase in overall testing rates, the OSP was associated with increased FOBT.

Ten-year changes in colorectal cancer screening in Switzerland: The Swiss Health Interview Survey 2007, 2012 and 2017.

Recent recommendations for colorectal cancer (CRC) screening suggest fecal occult blood test (FOBT) or colonoscopy. Since 2013, mandatory health insurance in Switzerland reimburse CRC screening. We set out to determine if CRC testing rate and type of CRC screening changed in Switzerland from 2007 to 2017 and between the three main language regions. We extracted data on 50-75-year-olds from the Swiss Health Interview Survey (SHIS) 2007, 2012 and 2017 to determine rates of self-reported testing with FOBT within last 2 years and colonoscopy within last 10 years. We estimated prevalence ratio (PR) in multivariate-adjusted logistic regression models and compared rates in German-, French- and Italian-speaking regions, adjusting for sociodemographic, self-rated health and insurance variables. Overall testing rates (FOBT or colonoscopy) increased in all regions from 2007 to 2017 (German-speaking 33.6% to 48.3%; French-speaking 30.8% to 48.8%; Italian-speaking 37.9% to 46.8%), mainly because of an increase in colonoscopy rate for screening reasons (p < 0.001 in all regions). Rates of FOBT testing fell significantly in the German-speaking region (11.9% to 4.4%, p < 0.001), but not in the Italian- (13.9% to 8.5%, p = 0.052) and French-speaking regions (7.6% to 7.4%, p = 0.138). Overall CRC testing rate rose from 33.2% in 2007 to 48.4% in 2017, mainly because of an increase of colonoscopy rate for screening reasons. Coverage remains below the 65% target of European guidelines. Organized screening programs encouraging FOBT screening could contribute to further increasing the CRC testing rate.

Incorporating Baseline Outcome Data in Individual Participant Data Meta-Analysis of Non-randomized Studies.

Background: In non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC). Methods: For the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA. Results: Ten of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score. Conclusion: ANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly.

Change in Colorectal Cancer Tests Submitted for Reimbursement in Switzerland 2012-2018: Evidence from Claims Data of a Large Insurance.

Objectives: Guidelines recommend colorectal cancer (CRC) screening by fecal occult blood test (FOBT) or colonoscopy. In 2013, Switzerland introduced reimbursement of CRC screening by mandatory health insurance for 50-69-years-olds, after they met their deductible. We hypothesized that the 2013 reimbursement policy increased testing rate. Methods: In claims data from a Swiss insurance, we determined yearly CRC testing rate among 50-75-year-olds (2012-2018) and the association with socio-demographic, insurance-, and health-related covariates with multivariate-adjusted logistic regression models. We tested for interaction of age (50-69/70-75) on testing rate over time. Results: Among insurees (2012:355'683; 2018:348'526), yearly CRC testing rate increased from 2012 to 2018 (overall: 8.1-9.9%; colonoscopy: 5.0-7.6%; FOBT: 3.1-2.3%). Odds ratio (OR) were higher for 70-75-year-olds (2012: 1.16, 95%CI 1.13-1.20; 2018: 1.05, 95%CI 1.02-1.08). Deductible interacted with changes in testing rate over time (p < 0.001). The increase in testing rate was proportionally higher among 50-69-years-olds than 70-75-year-olds over the years. Conclusions: CRC testing rate in Switzerland increased from 2012 to 2018, particularly among 50-69-years-olds, the target population of the 2013 law. Future studies should explore the effect of encouraging FOBT or waiving deductible.

Development and validation of a life expectancy estimator for multimorbid older adults: a cohort study protocol.

BACKGROUND: Older multimorbid adults have a high risk of mortality and a short life expectancy (LE). Providing high-value care and avoiding care overuse, including of preventive care, is a serious challenge among multimorbid patients. While guidelines recommend to tailor preventive care according to the estimated LE, there is no tool to estimate LE in this specific population. Our objective is therefore to develop an LE estimator for older multimorbid adults by transforming a mortality prognostic index, which will be developed and internally validated in a prospective cohort. METHODS AND ANALYSIS: We will analyse data of the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People cohort study in Bern, Switzerland. 822 participants were included at hospitalisation with age of 70 years or older, multimorbidity (three or more chronic medical conditions) and polypharmacy (use of five drugs or more for >30 days). All-cause mortality will be assessed during 3 years of follow-up. We will apply a flexible parametric survival model with backward stepwise selection to identify the mortality risk predictors. The model will be internally validated using bootstrapping techniques. We will derive a point-based risk score from the regression coefficients. We will transform the 3-year mortality prognostic index into an LE estimator using the Gompertz survival function. We will perform a qualitative assessment of the clinical usability of the LE estimator and its application. We will conduct the development and validation of the mortality prognostic index following the Prognosis Research Strategy (PROGRESS) framework and report it following the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement. ETHICS AND DISSEMINATION: Written informed consent by patients themselves or, in the case of cognitive impairment, by a legal representative, was required before enrolment. The local ethics committee (Kantonale Ethikkommission Bern) has approved the study. We plan to publish the results in peer-reviewed journals and present them at national and international conferences.

Novel bleeding risk score for patients with atrial fibrillation on oral anticoagulants, including direct oral anticoagulants.

OBJECTIVE: Balancing bleeding risk and stroke risk in patients with atrial fibrillation (AF) is a common challenge. Though several bleeding risk scores exist, most have not included patients on direct oral anticoagulants (DOACs). We aimed at developing a novel bleeding risk score for patients with AF on oral anticoagulants (OAC) including both vitamin K antagonists (VKA) and DOACs. METHODS: We included patients with AF on OACs from a prospective multicenter cohort study in Switzerland (SWISS-AF). The outcome was time to first bleeding. Bleeding events were defined as major or clinically relevant non-major bleeding. We used backward elimination to identify bleeding risk variables. We derived the score using a point score system based on the ß-coefficients from the multivariable model. We used the Brier score for model calibration (<0.25 indicating good calibration), and Harrel's c-statistics for model discrimination. RESULTS: We included 2147 patients with AF on OAC (72.5% male, mean age 73.4 ± 8.2 years), of whom 1209 (56.3%) took DOACs. After a follow-up of 4.4 years, a total of 255 (11.9%) bleeding events occurred. After backward elimination, age > 75 years, history of cancer, prior major hemorrhage, and arterial hypertension remained in the final prediction model. The Brier score was 0.23 (95% confidence interval [CI] 0.19-0.27), the c-statistic at 12 months was 0.71 (95% CI 0.63-0.80). CONCLUSION: In this prospective cohort study of AF patients and predominantly DOAC users, we successfully derived a bleeding risk prediction model with good calibration and discrimination.

Treating insomnia in Swiss primary care practices: A survey study based on case vignettes.

Guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as first-line treatment for chronic insomnia, but it is not clear how many primary care physicians (PCPs) in Switzerland prescribe this treatment. We created a survey that asked PCPs how they would treat chronic insomnia and how much they knew about CBT-I. The survey included two case vignettes that described patients with chronic insomnia, one with and one without comorbid depression. PCPs also answered general questions about treating chronic insomnia and about CBT-I and CBT-I providers. Of the 820 Swiss PCPs we invited, 395 (48%) completed the survey (mean age 54 years; 70% male); 87% of PCPs prescribed sleep hygiene and 65% phytopharmaceuticals for the patient who had only chronic insomnia; 95% prescribed antidepressants for the patient who had comorbid depression. In each case, 20% of PCPs prescribed benzodiazepines or benzodiazepine receptor agonists, 8% prescribed CBT-I, 68% said they knew little about CBT-I, and 78% did not know a CBT-I provider. In the clinical case vignettes, most PCPs treated chronic insomnia with phytopharmaceuticals and sleep hygiene despite their lack of efficacy, but PCPs rarely prescribed CBT-I, felt they knew little about it, and usually knew no CBT-I providers. PCPs need more information about the benefits of CBT-I and local CBT-I providers and dedicated initiatives to implement CBT-I in order to reduce the number of patients who are prescribed ineffective or potentially harmful medications.

Association between marijuana use and electrocardiographic abnormalities by middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: To evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD). DESIGN: Longitudinal and cross-sectional secondary data analysis from the CARDIA (Coronary Artery Risk Development in Young Adults) study. SETTING: Four communities in the United States. PARTICIPANTS: A total of 2585 participants from the 5115 black and white men and women recruited at age 18-30 years in 1985 to 1986 in CARDIA. MEASUREMENTS: ECG abnormalities coded as minor and major abnormalities with the Minnesota code of electrocardiographic findings at year 20. Self-reported current (past 30 days) and computed cumulative life-time marijuana use (one 'marijuana-year' corresponds to 365 days of use) through assessments every 2-5 years. We fitted logistic regression models adjusting for sex, race, center, education, age, tobacco smoking, physical activity, alcohol use and body mass index. FINDINGS: Among the 2585 participants with an ECG at year 20, mean age was 46, 57% were women, 45% were black; 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy-three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable-adjusted models, the odds ratio (OR) for major ECG abnormalities was 0.60 [95% confidence interval (CI) = 0.32-1.15] and for minor ECG abnormalities 1.21 (95% CI = 0.87-1.68). Results did not change after stratifying by sex and race. Cumulative marijuana use was not associated with ECG abnormalities. CONCLUSION: In a middle-aged US population, life-time cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated.

Sodium intake, life expectancy, and all-cause mortality.

AIMS: Since dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, a high sodium intake can be expected to curtail life span. We tested this hypothesis by analysing the relationship between sodium intake and life expectancy as well as survival in 181 countries worldwide. METHODS AND RESULTS: We correlated age-standardized estimates of country-specific average sodium consumption with healthy life expectancy at birth and at age of 60 years, death due to non-communicable diseases and all-cause mortality for the year of 2010, after adjusting for potential confounders such as gross domestic product per capita and body mass index. We considered global health estimates as provided by World Health Organization. Among the 181 countries included in this analysis, we found a positive correlation between sodium intake and healthy life expectancy at birth (ß = 2.6 years/g of daily sodium intake, R2 = 0.66, P < 0.001), as well as healthy life expectancy at age 60 (ß = 0.3 years/g of daily sodium intake, R2 = 0.60, P = 0.048) but not for death due to non-communicable diseases (ß = 17 events/g of daily sodium intake, R2 = 0.43, P = 0.100). Conversely, all-cause mortality correlated inversely with sodium intake (ß = -131 events/g of daily sodium intake, R2 = 0.60, P < 0.001). In a sensitivity analysis restricted to 46 countries in the highest income class, sodium intake continued to correlate positively with healthy life expectancy at birth (ß = 3.4 years/g of daily sodium intake, R2 = 0.53, P < 0.001) and inversely with all-cause mortality (ß = -168 events/g of daily sodium intake, R2 = 0.50, P < 0.001). CONCLUSION: Our observation of sodium intake correlating positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries argues against dietary sodium intake being a culprit of curtailing life span or a risk factor for premature death. These data are observational and should not be used as a base for nutritional interventions.

An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I2 = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I2 = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Prevalence and management of chronic insomnia in Swiss primary care: Cross-sectional data from the "Sentinella" practice-based research network.

We investigated the prevalence and treatment of patients with chronic insomnia presenting to Swiss primary care physicians (PCPs) part of "Sentinella", a nationwide practice-based research network. Each PCP consecutively asked 40 patients if they had sleep complaints, documented frequency, duration, comorbidities, and reported ongoing treatment. We analysed data of 63% (83/132) of the PCPs invited. The PCPs asked 76% (2,432/3,216) of included patients about their sleep (51% female); 31% (761/2,432) of these had had insomnia symptoms; 36% (875/2,432) had current insomnia symptoms; 11% (269/2,432) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for chronic insomnia (61% female). In all, 75% (201/269) of patients with chronic insomnia had comorbidities, with 49% (99/201) reporting depression. Chronic insomnia was treated in 78% (209/269); 70% (188/268) took medication, 38% (102/268) benzodiazepines or benzodiazepine receptor agonists, 32% (86/268) took antidepressants. Only 1% (three of 268) had been treated with cognitive behavioural therapy for insomnia (CBT-I). A third of patients presenting for a non-urgent visit in Swiss primary care reported insomnia symptoms and 11% met the DSM-5 criteria for chronic insomnia. Hypnotics were the most common treatment, but almost no patients received first-line CBT-I. Reducing the burden of insomnia depends on disseminating knowledge about and access to CBT-I, and encouraging PCPs to discuss it with and offer it as a first-line treatment to patients with chronic insomnia.

Low Reporting of Cointerventions in Recent Cardiovascular Clinical Trials: A Systematic Review.

Background A cointervention in a randomized clinical trial (RCT) is medical care given in addition to the tested intervention. If cointerventions are unbalanced between trial arms, the results may be biased. We hypothesized that cointerventions would be more adequately reported in RCTs without full blinding or at risk of bias. Methods and Results To describe the reporting of cointerventions and to evaluate the factors associated with their reporting, we did a systematic search of all RCTs evaluating pharmacological interventions on cardiovascular outcomes published in 5 high-impact journals. The reporting of cointerventions, blinding, and risk of bias were extracted and evaluated independently by 2 reviewers (E.M., L.A.). Cointerventions were inadequately reported in 87 of 123 RCTs (70.7%), with 56 (45.5%) providing no information on cointerventions and 31 (25.2%) providing only partial information. Of the RCTs, 52 (42.3%) had inadequate blinding of participants and/or personnel and 63 (51.2%) of the RCTs were judged at risk of bias. In univariable analysis, the reporting of cointerventions was not associated with blinding of participants and/or personnel (odds ratio [OR], 1.04; 95% CI, 0.47-2.27 for adequately versus inadequately blinded trials) or with risk of bias (OR, 1.47; 95% CI, 0.67-3.21 for at low risk of bias versus trials at risk of bias). In multivariable analysis, only a follow-up of <1 month was associated with the adequate reporting of cointerventions (OR, 3.63; 95% CI, 1.21-10.91). Conclusions More than two-thirds of recent major cardiovascular trials did not adequately report cointerventions. The quality of reporting was not better among trials that were not fully blinded or at risk for bias. Registration URL: https://www.crd.york.ac.uk/PROSP​ERO/. Unique identifier: CRD42018106771.

Association between colorectal cancer testing and insurance type: Evidence from the Swiss Health Interview Survey 2012.

Both colonoscopy and fecal occult blood test (FOBT) are commonly used for colorectal cancer (CRC) screening, but colonoscopy costs much more than FOBT. Swiss insurance offers high or low deductibles and choice of basic or private insurance. We hypothesized that high deductibles and basic insurance discourage colonoscopy, but do not change FOBT rates. We determined the proportion of patients tested for CRC in Switzerland (colonoscopy within 10 years, FOBT within 2 years), and determined associations with health insurance type. We extracted data on 50-75-year-olds from the Swiss Health Interview Surveys of 2012 to determine colonoscopy and FOBT testing rates (n = 7335). Multivariate logistic regression models estimated prevalence ratios (PRs) of CRC testing associated with health insurance type (deductible and private insurance), adjusted for socio-demographic factors (age, gender, education, income) and self-rated health. The weighted proportion of individuals tested for CRC within recommended intervals was 39.5%. Testing with colonoscopy was significantly associated with private insurance (PR 1.85, 95% CI: 1.46-2.35) and low deductible (PR 2.00, 95% CI: 1.56-2.57). Testing with FOBT was significantly associated with deductible (PR 1.71, 95%CI:1.09-2.68) but not with private insurance. About 60% of the Swiss population was not current with CRC testing. After adjusting for covariates, private insurance and low deductible was significantly associated with higher prevalence of CRC testing, indicating that waiving the deductible could increase CRC screening uptake and reduce health inequality.

Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies.

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. METHODS AND ANALYSIS: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. PROSPERO REGISTRATION NUMBER: CRD42018091627.

Caesarean section in uninsured women in the USA: systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to assess the odds of caesarean section (CS) for uninsured women in the USA and understand the underlying mechanisms as well as consequences of lower use. STUDY DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library and CINAHL from the first year of records to April 2018. ELIGIBILITY CRITERIA: We included studies that reported data to allow the calculation of ORs of CS of uninsured as compared with insured women. OUTCOMES: The prespecified primary outcome was the adjusted OR of deliveries by CS of uninsured women as compared with privately or publicly insured women. The prespecified secondary outcome was the crude OR of deliveries by CS of uninsured women as compared with insured women. RESULTS: 12 articles describing 16 separate studies involving more than 8.8 million women were included in this study. We found: 0.70 times lower odds of CS in uninsured as compared with privately insured women (95% CI 0.63 to 0.78), with no relevant heterogeneity between studies (τ2=0.01); and 0.92 times lower odds for CS in uninsured as compared with publicly insured women (95% CI 0.80 to 1.07), with no relevant heterogeneity between studies (τ2=0.02). We found 0.70 times lower odds in uninsured as compared with privately and publicly insured women (95% CI 0.69 to 0.72). CONCLUSIONS: CSs are less likely to be performed in uninsured women as compared with insured women. While the higher rates for CS among privately insured women can be explained with financial incentives associated with private insurance, the lower odds among uninsured women draw attention at barriers to access for delivery care. In many regions, the rates for uninsured women are above, close or below the benchmarks for appropriate CS rates and could imply both, underuse and overuse.

Caesarean sections and private insurance: systematic review and meta-analysis.

OBJECTIVE: Financial incentives associated with private insurance may encourage healthcare providers to perform more caesarean sections. We therefore sought to determine the association of private insurance and odds of caesarean section. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase and The Cochrane Library from the first year of records through August 2016. ELIGIBILITY CRITERIA: We included studies that reported data to allow the calculation of OR of caesarean section of privately insured as compared with publicly insured women. OUTCOMES: The prespecified primary outcome was the adjusted OR of births delivered by caesarean section of women covered with private insurance as compared with women covered with public insurance. The prespecified secondary outcome was the crude OR of births delivered by caesarean section of women covered with private insurance as compared with women covered with public insurance. RESULTS: Eighteen articles describing 21 separate studies in 12.9 million women were included in this study. In a meta-analysis of 13 studies, the adjusted odds of delivery by caesarean section was 1.13 higher among privately insured women as compared with women with public insurance coverage (95% CI 1.07 to 1.18) with no relevant heterogeneity between studies (τ2=0.006). The meta-analysis of crude estimates from 12 studies revealed a somewhat more pronounced association (pooled OR 1.35, 95% CI 1.27 to 1.44) with no relevant heterogeneity between studies (τ2=0.011). CONCLUSIONS: Caesarean sections are more likely to be performed in privately insured women as compared with women using public health insurance coverage. Although this effect is small on average and variable in its magnitude, it is present in all analyses we performed.

Thyroid Function Tests in the Reference Range and Fracture: Individual Participant Analysis of Prospective Cohorts.

Context: Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective: To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design: Individual participant data analysis. Setting: Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants: Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures: Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results: During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions: Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.

Caesarean sections and for-profit status of hospitals: systematic review and meta-analysis.

OBJECTIVE: Financial incentives may encourage private for-profit providers to perform more caesarean section (CS) than non-profit hospitals. We therefore sought to determine the association of for-profit status of hospital and odds of CS. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the first year of records through February 2016. ELIGIBILITY CRITERIA: To be eligible, studies had to report data to allow the calculation of ORs of CS comparing private for-profit hospitals with public or private non-profit hospitals in a specific geographic area. OUTCOMES: The prespecified primary outcome was the adjusted OR of births delivered by CS in private for-profit hospitals as compared with public or private non-profit hospitals; the prespecified secondary outcome was the crude OR of CS in private for-profit hospitals as compared with public or private non-profit hospitals. RESULTS: 15 articles describing 17 separate studies in 4.1 million women were included. In a meta-analysis of 11 studies, the adjusted odds of delivery by CS was 1.41 higher in for-profit hospitals as compared with non-profit hospitals (95% CI 1.24 to 1.60) with no relevant heterogeneity between studies (τ2≤0.037). Findings were robust across subgroups of studies in stratified analyses. The meta-analysis of crude estimates from 16 studies revealed a somewhat more pronounced association (pooled OR 1.84, 95% CI 1.49 to 2.27) with moderate-to-high heterogeneity between studies (τ2≥0.179). CONCLUSIONS: CS are more likely to be performed by for-profit hospitals as compared with non-profit hospitals. This holds true regardless of women's risk and contextual factors such as country, year or study design. Since financial incentives are likely to play an important role, we recommend examination of incentive structures of for-profit hospitals to identify strategies that encourage appropriate provision of CS.