Cohort Entry Date Research Articles

Statin Therapy and the Risk of Osteoporotic Fractures in Patients with Metabolic Syndrome: a Nested Case-Control Study.

ObjectiveWe aimed to investigate the association between statin use and the risk of major osteoporotic fractures in patients with metabolic syndrome (MetS).MethodsA nested case-control study was performed in patients with MetS (≥50 years) who had no history of osteoporotic fracture using the Korean National Health Insurance Service-Health Screening Cohort. This study included 17,041 patients diagnosed with new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsDuring a 4-year follow-up period, the risk of major osteoporotic fractures was significantly reduced by 9% (OR, 0.91; 95% CI, 0.85–0.97) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for vertebral fracture (OR, 0.86; 95% CI, 0.79–0.94) but not for non-vertebral fracture (OR, 0.97; 95% CI, 0.88–1.06). Longer duration (OR, 0.97; 95% CI, 0.96–0.99, per 1-year increase) and higher cumulative dose (OR, 0.97; 95% CI, 0.95–0.99, per 365 defined daily doses) of statins were negatively associated with the risk of major osteoporotic fracture.ConclusionThis study supports the hypothesis that statin therapy has a beneficial effect on major osteoporotic fractures, especially vertebral fractures, in patients with MetS.

Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Venous Thromboembolism in Patients with Type 2 Diabetes: A Cohort Study

PurposeWe assessed whether sodium-glucose co-transporter type 2 (SGLT2) inhibitors are associated with a higher incidence rate of venous thromboembolism in patients with type 2 diabetes. MethodsWe conducted a population-based cohort study using the InGef database including patients with type 2 diabetes newly treated with noninsulin antidiabetic drugs between 2012 and 2018. Cases of venous thromboembolism identified during follow-up were matched to 40 controls on age, sex, cohort entry date, and duration of follow-up. Using a nested case-control approach, conditional logistic regression estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) of venous thromboembolism adjusted for sociodemographic and clinical variables, comparing current use of SGLT2 inhibitors with current use of dipeptidyl peptidase-4 (DPP-4) inhibitors. ResultsIn a cohort of 219,538 patients, we identified 2152 cases of venous thromboembolism and matched them to 85,104 controls. Compared with DPP-4 inhibitors, current use of SGLT2 inhibitors was associated with a lower rate of venous thromboembolism (RR, 0.75; 95% CI, 0.59-0.94). Effect estimates were similar for dapagliflozin (RR, 0.77; 95% CI, 0.57-1.03) and empagliflozin (RR, 0.71; 95% CI, 0.52-0.98). ConclusionsCompared with DPP-4 inhibitors, SGLT2 inhibitors were not associated with a higher rate of venous thromboembolism, providing reassurance regarding their thromboembolic safety.

US veterans administration diabetes risk (VADR) national cohort: cohort profile

PurposeThe veterans administration diabetes risk (VADR) cohort facilitates studies on temporal and geographic patterns of pre-diabetes and diabetes, as well as targeted studies of their predictors. The cohort provides an...

Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: a disease risk score-matched nested case\u2013control study

BackgroundExacerbation of chronic obstructive pulmonary disease (COPD) severely impacts the quality of life and causes high mortality and morbidity. COPD is involved with systemic and pulmonary inflammation, which may be attenuated with antidiabetic agents exerting anti-inflammatory effects. Real-world evidence is scant regarding the effects of antidiabetic agents on COPD exacerbation. Accordingly, we conducted a disease risk score (DRS)-matched nested case–control study to systemically assess the association between each class of oral hypoglycemic agents (OHAs) and risk of severe COPD exacerbation in a nationwide COPD population co-diagnosed with diabetes mellitus (DM).MethodsWe enrolled 23,875 COPD patients receiving at least one OHA for management of DM by analyzing the Taiwan National Health Insurance claims database between January 1, 2000, and December 31, 2015. Cases of severe exacerbation were defined as those who had the first hospital admission for COPD. Each case was individually matched with four randomly-selected controls by cohort entry date, DRS (the estimated probability of encountering a severe COPD exacerbation), and COPD medication regimens using the incidence density sampling approach. Conditional logistic regressions were performed to estimate odds ratios (OR) of severe COPD exacerbation for each type of OHAs.ResultsWe analyzed 2700 cases of severe COPD exacerbation and 9272 corresponding controls after DRS matching. Current use of metformin versus other OHAs was associated with a 15% (adjusted OR [aOR], 0.85; 95% confidence interval [CI] 0.75–0.95) reduced risk of severe COPD exacerbation, whereas the reduced risk was not observed with other types of antidiabetic agents. When considering the duration of antidiabetic medication therapy, current use of metformin for 91–180 and 181–365 days was associated with a 28% (aOR, 0.72; 95% CI 0.58–0.89) and 37% (aOR, 0.63; 95% CI 0.51–0.77) reduced risk of severe COPD exacerbation, respectively. Similarly, 91–180 days of sulfonylureas therapy led to a 28% (aOR, 0.72; 95% CI 0.58–0.90) lower risk, and longer treatments consistently yielded 24–30% lower risks. Current use of thiazolidinediones for more than 181 days yielded an approximately 40% decreased risk.ConclusionsDuration-dependent beneficial effects of current metformin, sulfonylurea, and thiazolidinedione use on severe COPD exacerbation were observed in patients with COPD and DM.

An assessment of the potential miscalibration of cardiovascular disease risk predictions caused by a secular trend in cardiovascular disease in England

BackgroundA downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Risk prediction models for primary prevention of CVD do not model this secular trend, this could result in over prediction of risk for individuals in the present day. We evaluate the effects of modelling this secular trend, and also assess whether it is driven by an increase in statin use during follow up.MethodsWe derived a cohort of patients (1998–2015) eligible for cardiovascular risk prediction from the Clinical Practice Research Datalink with linked hospitalisation and mortality records (N = 3,855,660). Patients were split into development and validation cohort based on their cohort entry date (before/after 2010). The calibration of a CVD risk prediction model developed in the development cohort was tested in the validation cohort. The calibration was also assessed after modelling the secular trend. Finally, the presence of the secular trend was evaluated under a marginal structural model framework, where the effect of statin treatment during follow up is adjusted for.ResultsSubstantial over prediction of risks in the validation cohort was found when not modelling the secular trend. This miscalibration could be minimised if one was to explicitly model the secular trend. The reduction in risk in the validation cohort when introducing the secular trend was 35.68 and 33.24% in the female and male cohorts respectively. Under the marginal structural model framework, the reductions were 33.31 and 32.67% respectively, indicating increasing statin use during follow up is not the only the cause of the secular trend.ConclusionsInclusion of the secular trend into the model substantially changed the CVD risk predictions. Models that are being used in clinical practice in the UK do not model secular trend and may thus overestimate the risks, possibly leading to patients being treated unnecessarily. Wider discussion around the modelling of secular trends in a risk prediction framework is needed.

Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study.

DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends. Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18-89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999-2006) and late cohort (2007-2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model. We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM. The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.

Application of a Medicare claims-based model predicting left ventricular ejection fraction subtype to investigate the epidemiology of heart failure in the US Medicare program

Abstract Introduction Administrative claims do not contain ejection fraction (EF) information for heart failure (HF) patients. To address this limitation, we recently developed a claims-based model to classify HF patients into reduced EF (rEF) or preserved EF (pEF) using 35 predictors. Purpose To report distribution of key patient characteristics and rates of HF decompensation and mortality in model-identified rEF and pEF patients from nationwide Medicare claims (2012–2016) and compare with estimates from the literature. Methods We identified HF patients ≥65 years from US Medicare claims using recorded diagnosis after ≥6 months of continuous enrollment. The date of HF diagnosis was the cohort entry date. The 6-month baseline period prior to the cohort entry date was used to identify predictors and apply the claims-based model to distinguish rEF and pEF. Patients were followed for the composite outcome of time to first HF decompensation (HF hospitalization or outpatient IV diuretic treatment) or all-cause mortality. Descriptive statistics were used to summarize baseline patient characteristics. Cumulative incidence estimates along with 95% confidence intervals (CI) were calculated for the composite endpoint as well as all-cause and cause-specific mortality (derived from National Death Index linkage) using the Kaplan-Meier method. Results A total of 3,134,414 HF patients with an average age of 79 years were identified, of which 200,950 (6.4%) were classified as rEF. Among those classified as rEF, men comprised a larger proportion (68% vs 41%), the average age was lower (76 vs 79 years), and history of myocardial infarction was more frequent (32% vs 13%) compared to pEF. One-year cumulative incidence (95% CI) of the composite endpoint was 42.6% (42.4–42.8%) for rEF and 36.9% (36.7–37.0%) for pEF. One-year all-cause mortality incidence was similar between the groups (27.4% [27.2–27.6%] for rEF and 26.4% [26.3–26.4%] for pEF), however, cardiovascular mortality was higher for rEF (16.7% [16.5–16.8%] vs 12.3% [12.2–12.3%]), whereas non-cardiovascular mortality was higher for pEF (12.9% [12.7–13.1%] vs 16.0% (16.0–16.1%) (Figure 1). These results were in line with estimates from other well-established cardiovascular cohorts including the Get With The Guidelines-HF cohort and the Olmstead County HF epidemiology cohort. Conclusion We replicated well-documented differences in key patient characteristics and endpoints between rEF and pEF in these populations identified based on application of a claims-based model. Our results support use of this model for identifying cohorts of rEF and pEF to conduct subtype specific investigations of treatment outcomes. However, a notably lower proportion of patients were identified as having rEF compared to previous reports indicating low sensitivity of this approach for rEF and suggesting that model-based classification may not be useful in tracking subtype specific incidence or prevalence of HF using Medicare claims. Cumulative incidence of outcomes in HF Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Novartis Inc.

Comparing proton pump inhibitors with histamin-2 receptor blockers regarding the risk of osteoporotic fractures: a nested case-control study of more than 350,000 Korean patients with GERD and peptic ulcer disease

BackgroundPatients with peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are more likely to receive long-term therapy with proton pump inhibitors (PPIs). This study aimed to investigate the risk of osteoporotic fractures in PPI users compared to histamine-2 receptor antagonist (H2RA) users and the association between fractures and the duration and regular use of PPI.MethodsA population-based, nationwide nested case-control study from January 2006 to December 2015 was performed using Korean National Health Insurance Service claims data. We included patients ≥50 years of age, without previous fractures, newly prescribed with PPI or H2RA, and diagnosed with PUD or GERD from 2006 to 2015. Patients with osteoporotic fracture (n = 59,240) were matched with the non-fracture control group (n = 296,200) at a 1:5 ratio based on sex, age, cohort entry date, follow-up duration, and bisphosphonate use. The osteoporotic fractures were defined using the diagnostic codes of claims data (M80, M81, M82, M484, M485, S220, S221, S320, S327, S422, S423, S525, S526, S72).ResultsThe higher the cumulative use of PPIs, the higher the osteoporotic fracture risk (P for trend < 0.001). The risk of osteoporotic fracture in the patients whose cumulative use of PPI was more than 1 year was higher than that of others (OR: 1.42, 95% CI: 1.32–1.52). Patients who regularly used PPI in the recent 1 year had a higher risk of osteoporotic fracture than exclusive H2RA users (OR: 1.37, 95% CI: 1.26–1.50).ConclusionsThe risk of osteoporotic fracture increased with the duration of PPI use, especially when PPI was used for ≥1 year and regularly in the recent 1 year.

Evaluation of Patients’ Adverse Events Associated With Contact Isolation: Matched Cohort Study With Propensity Score

Background: Contact isolation (ie, patient isolation with contact precautions) has been frequently used for preventing healthcare-associated infections caused by epidemiologically important pathogens (eg, vancomycin-resistant enterococcus [VRE]) via direct or indirect contact with patients. Based on ineffective components of routine contact isolations (eg, fewer healthcare provider visits), some studies have reported an association between the likelihood of adverse events and contact isolation. Objective: Given no strong evidence for this association due to most studies’ invalid study designs and systematic misclassification, we compared adverse events between a VRE isolation cohort and a matched comparison cohort, using a propensity score matching cohort study design. Methods: This study was conducted at a 1,337-bed, tertiary-care, university-affiliated, Korean hospital equipped with a full electronic medical record (EMR) system for all patient records. With institutional review board approval, all relevant EMR records were extracted for the study period 2015–2017. All contact isolation information of VRE patients were confirmed through EMR manual review by 1 trained research nurse. For propensity score matching, risk factors for adverse events (ie, decubitus ulcer, fall, and cardiopulmonary resuscitation [CPR]) were selected based on literature reviews: length of stay, age, gender, diabetes mellitus, hypertension, albumin, Charlson comorbidity index, Braden scale score, and Hendrich II fall risk. For each VRE case, the 1:1 matched case was selected through the nearest neighbor matching with calculated propensity scores. The retrospective observation period was from the cohort entry date (ie, contact isolation start date) to the cohort exit date (ie, discharge or discontinue of contact isolation). A time-to-event analysis with a Cox proportional hazard model was conducted using SAS version 9.4 software. Results: Among the 98,527 inpatients (323 VRE positive; 98,204 VRE negative), the VRE cohort (N = 141 of 216, 65% of total VRE patients admitted to general wards without adverse event history before contact isolation) and the matched comparison (no isolation) cohort (N = 141, 0.1%) showed no differences in characteristic comparisons (Table 1). The Cox proportional hazard model was not applicable for CPR because no CPR case was available in the matched comparison cohort. The hazard ratios for adverse events showed no statistically significant difference for both cohorts: decubitus ulcer (hazard ratio [HR], 1.049; 95% CI, 0.328–3.352; fall (HR, 0.418; 95% CI, 0.051–3.349) (Table 2). Conclusions: Based on the full EMR records for 3 years, our propensity-score–matched cohort study reported no association between the likelihoods of adverse events and contact isolation.Funding: This work was supported by the Collaborative Research Program of Medical Science and Nursing Science from Seoul National University College of Medicine (Grant no. 800-20180001 &amp; 810-20180001).Disclosures: None.

Sacubitril/valsartan vs. angiotensin receptor inhibition in heart failure: a real-world study in Taiwan.

AimsThis study aimed to compare the efficacy of angiotensin receptor–neprilysin inhibitor (ARNI) therapy with angiotensin receptor blocker (ARB) therapy for cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction.Methods and resultsData were obtained from the Chang Gung Research Database. The cohort entry date of the ARB group was assigned as that of the ARNI group to avoid immortal time bias. Additionally, 1:1 propensity score matching based on age, sex, and baseline left ventricular ejection fraction was conducted. The expectation–maximization imputation method with inverse probability of treatment weighting was used to compare outcomes between the two groups. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. Patients who received ARNI therapy had a significantly lower risk of the primary composite outcome occurring than patients who received ARBs (hazard ratio, 0.74; 95% confidence interval, 0.57–0.96). The reduction of hospitalization for worsening HF contributed most to the primary outcome benefits. In addition to the primary outcome, the ARNI group had a significantly lower risk of non‐fatal myocardial infarction. The improvement of ejection fraction was not significantly different between the groups. The medication doses of ARNI were lower than in clinical trials.ConclusionsIn patients with HF with reduced ejection fraction, sacubitril/valsartan was superior to ARB therapy in reducing the occurrence of the primary outcome endpoint of hospitalization for worsening HF and cardiovascular death.

Increased risk of death associated with the use of proton-pump inhibitors in patients with dementia and controls - a pharmacoepidemiological claims data analysis.

Background and purposeThe use of proton‐pump inhibitors (PPIs) was reported to be associated with increased mortality risk and has been proposed as a potential risk factor for neurodegenerative diseases. We aimed to assess the impact of PPI use on survival in patients with dementia as compared with controls.MethodsThis register‐based control‐matched cohort study included 28 428 patients with dementia ascertained by the prescription of antidementia drugs and two control individuals matched by sex, age and area of residence for each patient with dementia during the study period from 1 January 2005 to 30 June 2016. Cumulative defined daily doses (DDDs) of PPIs were extracted from the health insurance prescription registries. A multivariate Cox regression model for non‐proportional hazards was used to analyse mortality risk in dependence of PPI exposure, which was limited to 1 year preceding the date of cohort entry (index date) in order to avoid immortal time bias.ResultsThe PPI exposure of 100 DDDs in the year before the index date was associated with an increased mortality risk in patients with dementia (adjusted hazard ratio, 1.07; 95% confidence intervals, 1.03–1.12), but also in controls (adjusted hazard ratio, 1.47; 95% confidence intervals, 1.31–1.64). The mortality risk in relation to PPI use was significantly lower in patients with dementia as compared with controls (P < 0.0001) and highest in the first 2 years after the index date in both cohorts.ConclusionsOur findings promote more stringent pharmacovigilance strategies to avoid PPI use in cases lacking a clear indication for therapy or where potential risks outweigh the benefits.

PCV44 RISK OF CARDIAC EVENTS IN IBRUTINIB-TREATED PATIENTS WITH LYMPHOID MALIGNANCIES

Ibrutinib is a novel therapy for the treatment of lymphoid malignancies. Case reports suggest an increased risk of cardiac side effects. The drug label for ibrutinib was updated by the FDA in 2017 to include a warning about a potential increased risk of ventricular fibrillation. The objective of this study is to estimate the risk of cardiac events associated with ibrutinib use in patients with Mantle Cell Lymphoma, Chronic Lymphocytic Lymphoma, or Wandenstorm’s macroglobunemia. Retrospective cohort study using IQVIA LifeLink Pharmetrics Plus dataset from 2013 to 2018. The cohort comprised patients with a diagnosis of Mantle Cell Lymphoma, Chronic Lymphocytic Lymphoma, or Wandenstorm’s macroglobunemia. Index date was defined as the date of first prescription of ibrutinib for the exposed and date of first prescription of any drug in case of non-exposed. Exposure was defined as having at least one prescription of ibrutinib during the study period. Non-exposed were selected based on the first prescription for any drug after the cohort entry date. Exposed and non-exposed were matched (1:5) on age (± 2 years), sex, and geographic region. A cardiac outcome was defined as having any of the following outcomes: ventricular fibrillation, ventricular flutter, polymorphic ventricular tachycardia, atrial fibrillation, sudden cardiac death, or conduction disorders within 6 months after index date. The final sample included 80 cases matched to 400 controls. The unadjusted relative risk of cardiac outcomes in patients receiving ibrutinib versus those receiving any other drug was 1.0002 (confidence interval [CI] = 0.9999-1.0005). Unadjusted results suggests no association between ibrutinib use and cardiac outcomes when compared to patients with lymphoid cancer receiving any other drug. Post hoc power calculation suggested that a RR of 2.1 would be necessary to detect an association with the current sample size suggesting a more robust study is needed.

Derivation and Validation of a Prediction Model for Venous Thromboembolism in Primary Care.

Most episodes of venous thromboembolism (VTE) occurred in primary care. To date, no score potentially able to identify those patients who may deserve an antithrombotic prophylaxis has been developed. The objective of this study is to develop and validate a prediction model for VTE in primary care. Using the Health Search Database, we identified a cohort of 1,359,880 adult patients between 2002 and 2013. The date of the first General Practitioner's (GP) visit was the cohort entry date. All VTE cases (index date) observed up to December 2014 were identified. The cohort was randomly divided in a development and a validation cohort. According to nested case-cohort analysis, up to five controls were matched to their respective cases on month and year of cohort entry and duration of follow-up.The score was evaluated according to explained variance (pseudo R2) as a performance measure, ratio of predicted to observed cases as model calibration and area under the curve (AUC) as discrimination measure. The score was able to explain 27.9% of the variation for VTE occurrence. The calibration measure revealed a margin of error lower than 10% in 70% of the population. In terms of discrimination, AUC was 0.82 (95% confidence interval: 0.82-0.83). Results of sensitivity analyses substantially confirmed these findings. The present score demonstrated a very good accuracy in predicting the risk of VTE in primary care. This score may be therefore implemented in clinical practice so aiding GPs in making decision on patients potentially at risk of VTE.

Comparative analysis of the risk of osteoporotic fractures with proton pump inhibitor use and histamine-2 receptor antagonist therapy in elderly women: A nationwide population-based nested case-control study.

The influence of proton pump inhibitors (PPIs) on the risk of osteoporotic fractures remains to be elucidated, especially in the Asian population. This study evaluated the risk of osteoporotic fractures in elderly female Korean PPI users compared to histamine-2 receptor antagonist (H2RA) users, as well as the relationship between fractures and the duration, dose, and pattern of use of PPI. We screened a nationwide cohort of elderly Korean women who underwent bone mineral density measurements during their 66-year-old life-transition medical examination between 2009 and 2014. Study subjects included 8903 cases diagnosed with new osteoporotic fractures and 44,515 matched controls (1:5 ratio based on cohort entry date, follow-up duration, and baseline osteoporosis status) without fractures. They were followed up until 2015. Information on the exposure to PPI or H2RA, occurrence of fracture, and covariates were obtained from the Korean National Health Insurance Service data. Covariate-adjusted odds ratio (aOR) and 95% confidence interval (CI) were estimated using conditional logistic regression analysis. PPI use was associated with an increased risk of osteoporotic fractures (aOR: 1.13, 95% CI: 1.07, 1.18) compared with H2RA-only use. Increasing duration of PPI use was positively associated with the risk of osteoporotic fracture [aOR (95% CI) of long-term PPI use (≥1year): 1.3 (1.09, 1.56)]. Recent PPI use within the last year was associated with an increased risk of fracture (aOR: 1.31, 95% CI: 1.23, 1.38), whereas remote PPI use was not (aOR: 0.98, 95% CI: 0.92, 1.04). The risk of fracture did not increase with the increasing cumulative PPI dose. Compared with the use of H2RA alone, PPI use was associated with an increased risk of osteoporotic fractures in elderly Korean women, particularly among those who had used PPI within the last year or for more than one year.

SGLT2 Inhibitors and the Risk of Hospitalization for Fournier's Gangrene: A Nested Case-Control Study.

IntroductionBased on post-marketing surveillance, concern has been raised that sodium–glucose cotransporter 2 inhibitors (SGLT2i) may increase the risk of necrotizing fasciitis of the perineum (Fournier’s gangrene, FG). As a result of the low incidence of FG, data from clinical trials may be insufficient to robustly assess this issue because of the relatively limited numbers of participants. Real-world evidence may help clarify the association between SGLT2i and FG in the type 2 diabetes (T2D) population.MethodsA nested case–control study was performed using Truven Health MarketScan™ databases. Each patient with T2D hospitalized for FG between 1 April 2013 (when the first SGLT2i was available) and 31 March 2018 (latest available data) was matched (on the basis of sex, age, and cohort entry date) with six controls from the same cohort. The adjusted odds ratio (OR) of hospitalization for FG was estimated for patients receiving SGLT2i compared with those receiving two or more non-SGLT2i antihyperglycemic agents (AHAs) or insulin alone using conditional logistic regression.ResultsThe cohort included 1,897,935 patients, with 216 hospitalized for FG (incidence rate, 5.2 events per 100,000 person-years). Patients with FG ranged from 23 to 79 years of age; 201 (93.1%) were men. Among the 216 FG cases, 9 (4.2%) were current SGLT2i users; among the 1296 matched controls, 100 (7.7%) were current SGLT2i users. Approximately 93% of SGLT2i were used in combination. The adjusted OR of FG in patients treated with SGLT2i compared with patients treated with two or more non-SGLT2i AHAs or insulin alone was 0.55 [95% CI 0.25–1.18].ConclusionThe study did not find that treatment with SGLT2i, as compared with treatment with two or more non-SGLT2i AHAs or insulin alone, was statistically significantly associated with an increased risk of hospitalization for FG. Additional studies are needed to corroborate the findings.

β 2-Agonists and the Incidence of Parkinson Disease.

A recent study found a decreased risk of Parkinson disease (PD) associated with the β2 adrenergic agonist (β2-agonist) salbutamol. However, other mechanisms might explain this apparent association. Using the UK Clinical Practice Research Datalink, we formed a cohort of 2,430,884 patients aged 50 years or older between 1995 and 2016. During follow-up, 8,604 cases of PD were identified and matched to 86,040 controls on sex, age, date of cohort entry, and duration of follow-up, after applying a 1-year latency time window. Incidence rate ratios of PD associated with use of β2-agonists were estimated using conditional logistic regression. Ever-use of β2-agonists was associated with a 17% decreased rate of PD (rate ratio =0.83, 95% confidence interval: 0.75, 0.91) compared with no use. However, this association was limited to early short-term use and was no longer observed after more than 2 years of cumulative duration of use (rate ratio =0.97, 95% confidence interval: 0.80, 1.17). A similar pattern was observed when stratifying by time since first β2-agonist prescription and by duration of follow-up. The apparent association of β2-agonists with a decreased risk of PD is likely the result of reverse causality rather than a biological effect of these drugs on the risk of PD.

Atopic eczema and fracture risk in adults: A population-based cohort study

BackgroundLimited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.ObjectiveWe sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.MethodsWe performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.ResultsWe identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.ConclusionsPeople with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.

Attained pregnancy among women with a prosthetic heart valve

BackgroundWomen with prosthetic heart valves are at higher risk for adverse outcomes during pregnancy. The rates of achieved pregnancy, regardless of the pregnancy outcome, are largely unknown in this group of women. ObjectiveTo determine the rate of pregnancy in women with prior heart valve replacement, and compare that to women without known heart disease. Study DesignA retrospective matched population-based cohort study was done between April 1994 and March 2017, in Ontario, Canada, where universal health care is available. Administrative healthcare databases were used to identify study participants, exposures and outcomes. Each woman of child-bearing age who had a bioprosthetic or mechanical mitral or aortic valve replacement (valve replacement group) was matched to four women without heart disease (community comparison group) -- by age, year of cohort entry, any recent prior pregnancy, geographic area of residence and income level. Starting after the date of cohort entry (defined as the date valve replacement date in the valve replacement group), participants were assessed for a recognized pregnancy, namely, a livebirth, stillbirth, miscarriage or induced abortion. Hazard ratios (HR) and 95% confidence intervals (CI) were further adjusted for age, immigrant status and comorbid medical conditions. Results1596 women with a valve replacement were matched with 6378 women in the community comparison group. After a median (interquartile range, IQR) duration of follow-up of 3.1 (1.0–5.6) and 2.7 (1.0–6.0) years, respectively, 98 women in the valve replacement group achieved a recognized pregnancy (0.63 per 100 person-years), compared to 607 women in the community comparison group (0.88 per 100 person-years) – an adjusted HR of 0.72 (95% CI 0.57-0.89). Within the valve replacement group, those with a mechanical valve were less likely to achieve a recognized pregnancy than those with a bioprosthetic valve (adjusted HR 0.57, 95% CI 0.38-0.87). ConclusionWomen who undergo aortic or mitral valve replacement are less likely to achieve a pregnancy than matched counterparts without heart disease. This information, and the reasons for why this is so, can inform decisions about the timing of valve replacement and pregnancy planning.

Adult Asthma among Workers in Ontario. Results from the Occupational Disease Surveillance System.

Rationale: Given that approximately 15% of new-onset adult asthma cases originate because of exposures in the workplace, there is a need for systematic and ongoing monitoring of risk among workers. Objectives: To characterize the risk of new-onset adult asthma among workers in Ontario. Methods: We used 575,379 provincial accepted time-loss workers' compensation claimants data linked to physician billing data. Workers aged 15 to 65 years with a nonasthma compensation claim between January 1, 2002, and December 31, 2013, were eligible for inclusion. Cohort entry corresponded to the date of the claim. The case definition required two or more records for asthma within a 12-month period, within a 3-year time window after cohort entry. A 3-year washout period preceding cohort entry was used to exclude prevalent cases. Workers at risk of new-onset adult asthma were followed from cohort entry date to date of diagnosis, emigration, age 65 years, death, or end of study period. Cox regression models were used to generate birth year- and sex-adjusted hazard ratios (HRs) by occupation, industry, and exposures identified using a job exposure matrix. Sex-stratified risk estimates were also generated. Results: Increased risks were detected among well-recognized groups, including bakers (HR, 1.60; 95% confidence interval [CI], 1.22-2.09) and painters and decorators (HR, 1.67; 95% CI, 1.23-2.28). In the job exposure matrix analysis, flour and isocyanates were associated with increased risk of asthma. Concrete finishers (HR, 1.93; 95% CI, 1.12-3.32) and shipping and receiving clerks (HR, 1.21; 95% CI, 1.03-1.43) also showed elevated risk, whereas results varied across woodworker groups. Decreased risks were detected for nursing and farming groups. Conclusions: This practical data linkage approach was successful for examining associations across hundreds of jobs. Unexpected and previously unrecognized findings deserve further investigation and emphasize the importance of an ongoing system to guide research as well as prevention.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits

ObjectivesTramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well...