Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

PURPOSE: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. METHODS: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. RESULTS: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. CONCLUSION: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.

Prescribing errors in children: what is the impact of a computerized physician order entry?

Prescribing errors represent a safety risk for hospitalized patients, especially in pediatrics. Computerized physician order entry (CPOE) might reduce prescribing errors, although its effect has not yet been thoroughly studied on pediatric general wards. This study investigated the impact of a CPOE on prescribing errors in children on general wards at the University Children's Hospital Zurich. We performed medication reviews on a total of 1000 patients before and after the implementation of a CPOE. The CPOE included limited clinical decision support (CDS) such as drug-drug interaction check and checks for duplicates. Prescribing errors, their type according to the PCNE classification, their severity (adapted NCC MERP index), as well as the interrater reliability (Cohen's kappa), were analyzed. Potentially harmful errors were significantly reduced from 18 errors/100 prescriptions (95% CI: 17-20) to 11 errors/100 prescriptions (95% CI: 9-12) after CPOE implementation. A large number of errors with low potential for harm (e.g., "missing information") was reduced after the introduction of the CPOE, and consequently, the overall severity of potential harm increased post-CPOE. Despite general error rate reduction, medication reconciliation problems (PCNE error 8), such as drugs prescribed on paper as well as electronically, significantly increased after the introduction of the CPOE. The most common pediatric prescribing errors, the dosing errors (PCNE errors 3), were not altered on a statistically significant level after the introduction of the CPOE. Interrater reliability showed moderate agreement (Κ = 0.48).  Conclusion: Patient safety increased by reducing the rate of prescribing errors after CPOE implementation. The reason for the observed increase in medication reconciliation problems might be the hybrid system with remaining paper prescriptions for special medication. The lacking effect on dosing errors could be explained by the fact that a web application CDS covering dosing recommendations (PEDeDose) was already in use before the implementation of the CPOE. Further investigations should focus on eliminating hybrid systems, interventions to increase the usability of the CPOE, and full integration of CDS tools such as automated dose checks into the CPOE. What is Known: • Prescribing errors, especially dosing errors, are a common safety threat for pediatric inpatients. •The introduction of a CPOE may reduce prescribing errors, though pediatric general wards are poorly studied. What is New: •To our knowledge, this is the first study on prescribing errors in pediatric general wards in Switzerland investigating the impact of a CPOE. •We found that the overall error rate was significantly reduced after the implementation of the CPOE. The severity of potential harm was higher in the post-CPOE period, which implies that low-severity errors were substantially reduced after CPOE implementation. Dosing errors were not reduced, but missing information errors and drug selection errors were reduced. On the other hand, medication reconciliation problems increased.

Association between glycemic control and risk of venous thromboembolism in diabetic patients: a nested case-control study.

BACKGROUND: Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM. METHODS: We conducted a nested case-control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders. RESULTS: We identified 2'653 VTE cases and 10'612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36-55% increased relative risk of VTE when compared to women with HbA1c > 6.5-7.0%. CONCLUSIONS: Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5-7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

Characterization of the deterioration of diabetes control in patients with a subsequent diagnosis of pancreatic cancer: A descriptive study.

BACKGROUND: Deterioration of diabetes control can be the first harbinger of pancreatic cancer. However, little is known about how to distinguish patients with pancreatic cancer-related diabetes deterioration from those with type 2 diabetes progression. We aimed to characterize the glycated hemoglobin (HbA1c) and body weight profile of pancreatic cancer patients with deteriorating diabetes before the cancer diagnosis. METHODS: Using data from the UK-based Clinical Practice Research Datalink (CPRD) GOLD, we established a study population including pancreatic cancer patients with diabetes deterioration in the >0.5-3 years before the cancer diagnosis and non-cancer patients with deterioration of type 2 diabetes (comparison group). Patients were considered to have diabetes deterioration if their glucose-lowering treatment was intensified. We characterized the longitudinal trajectories of HbA1c and body weight in pancreatic cancer patients compared with non-cancer patients before and after treatment intensification. RESULTS: The mean absolute increase in HbA1c from the pre-deterioration period, i.e. the time >1-2 years before treatment intensification, to the time of treatment intensification, was 1.5% ± 1.6% in pancreatic cancer patients vs. 0.9% ± 1.4% in non-cancer patients. After treatment intensification, mean HbA1c remained elevated in pancreatic cancer patients, while it returned to the pre-deterioration level in non-cancer patients. Body weight decreased by 1.9% ± 6.4% in cancer patients and increased by 0.3% ± 5.2% in non-cancer patients between the pre-deterioration period and treatment intensification, on average. CONCLUSIONS: Pancreatic cancer-related diabetes deterioration may frequently be characterized by pronounced increases in HbA1c, persistent elevation of HbA1c after treatment intensification, and concomitant weight loss.

The Risk of Muscular Events Among New Users of Hydrophilic and Lipophilic Statins: an Observational Cohort Study.

BACKGROUND: Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells. OBJECTIVE: To compare the risk of muscular events between statins at comparable lipid-lowering doses and to evaluate if hydrophilic statins are associated with a lower muscular risk than lipophilic statins. DESIGN/SETTING: Propensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD. PATIENTS: New statin users. Cohort 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic), cohort 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic), and cohort 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg. MAIN MEASURES: The outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year. KEY RESULTS: The propensity score-matched cohorts consisted of 1) 9,703, 2) 7,032, and 3) 37,743 pairs of statin users. Comparing the risk of muscular events between low-intensity pravastatin vs low-intensity simvastatin yielded a HR of 0.86 (95% CI 0.64-1.16). In the comparison of moderate- to high-intensity rosuvastatin vs equivalent doses of atorvastatin, we observed a HR of 1.17 (95% CI 0.88-1.56). Moderate- to high-intensity simvastatin was associated with a HR of 1.33 (95% CI 1.16-1.53), when compared with atorvastatin at equivalent doses. LIMITATIONS: We could not conduct other pairwise comparisons of statins due to small sample size. In the absence of a uniform definition on the comparability of statin doses, the applied dose ratios may not fully match with all literature sources. CONCLUSIONS: Our results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.

Antiseizure drugs and risk of developing smoking-related chronic obstructive pulmonary disease or lung cancer: A population-based case-control study.

AIMS: To determine whether enzyme-inducing antiseizure drugs (ASDs) affect the risk of developing chronic obstructive pulmonary disease (COPD) or lung cancer in smokers. METHODS: Cases of COPD and lung cancer and matched controls without these conditions were identified from a population of smokers with ≥1 prescription for any type of ASD in the Clinical Practice Research Datalink UK database of patients managed in primary care (1995-2016). A matched case-control study was performed utilising multivariate logistic regression analyses of exposure to enzyme-inducing ASDs compared to non-enzyme-inducing ASDs. The duration of ASD exposure and level of tobacco exposure were also assessed. RESULTS: We identified 5952 incident COPD and 1373 incident lung cancer cases, and 59 328 and 13 681 matched controls, respectively. Compared with never use, ever use of enzyme-inducing ASDs was associated with slightly decreased risk estimates of COPD (adjusted odds ratio: 0.85, 95% confidence interval: 0.81-0.89) and lung cancer (adjusted odds ratio: 0.82, 95% confidence interval: 0.73-0.92). These risk estimates were attenuated in heavy smokers. CONCLUSION: We found slightly decreased risk estimates of COPD and lung cancer among smokers taking enzyme-inducing ASDs and hypothesise that this may be related to induction of detoxification of tobacco-specific lung toxins.

Validity of bariatric surgery codes in the UK Clinical Practice Research Datalink (CPRD) GOLD compared with Hospital Episodes Statistics.

OBJECTIVES: To assess completeness and validity of bariatric surgery codes in the UK Clinical Practice Research Datalink (CPRD) GOLD compared with Hospital Episodes Statistics (HES). METHODS: We conducted a validation study among patients in the UK-based CPRD GOLD with linkage to HES (1998 to 2017). Since the same surgery codes are used for bariatric and other gastrointestinal surgery we assessed code distribution patterns used in patients with bariatric versus other gastrointestinal surgery by presence of other conditions such as obesity and gastrointestinal cancer. We developed algorithms to identify bariatric surgery and calculated validity measures (ie, positive/negative predictive value [PPV/NPV], sensitivity, and specificity) of each in CPRD GOLD compared with HES (gold standard). RESULTS: Among 7 357 007 available patients we identified 10 190 patients who had a total of 14 046 potential bariatric surgery codes in CPRD GOLD and/or HES. Surgery code patterns differed between bariatric surgery and assumed other gastrointestinal surgery. The sensitivity of CPRD GOLD bariatric surgery coding improved from an overall of 56% to 69-71% when applying stricter algorithms (ie, in obese patients or obese, gastrointestinal disease/complication free patients) but PPVs remained at 53%-55%. NPVs and specificities of CPRD GOLD bariatric surgery coding achieved ≥99.8% for all algorithms. CONCLUSION: Our results suggest that using CPRD GOLD and HES data and a wide selection of surgery codes will result in the most complete and accurate capture of bariatric surgery events. Validity measures of CPRD GOLD bariatric surgery codes were identical in obese patients and more restrictive populations.

Use of selective serotonin reuptake inhibitors, other antidepressant medication, and risk of cataract: a case-control study based on Swiss claims data.

PURPOSE: Three previous studies reported controversial results regarding selective serotonin reuptake inhibitor (SSRI) exposure and cataract development. We therefore aimed to assess risk of cataract associated with previous exposure to SSRI using data from a large health insurance in Switzerland. METHODS: In a case-control study, we analyzed individuals insured by the Helsana Group, a large Swiss health insurance provider. We matched patients aged 40 years or older with cataract extraction (i.e., a proxy for a cataract diagnosis) in 2014 or 2015 to four control patients, on age, sex, date of cataract extraction, and area of residence. Exposure of interest was the number of SSRI claims prior to cataract extraction. We conducted conditional logistic regression analyses to calculate odds ratios (OR) with 95% confidence intervals (CI). We adjusted our analyses for the presence of hypertension, diabetes, glaucoma, systemic steroid use, and use of other antidepressant drugs. RESULTS: We identified 13,773 cataract cases and 51,625 matched controls. Compared with non-use, long-term use of SSRI (≥ 20 claims) was not associated with an altered risk of cataract (adjusted OR 0.93, 95% CI 0.84-1.04). The analysis of the individual drug substances also yielded no statistically significant association between drug exposure and the risk of cataract. CONCLUSIONS: According to our study, use of SSRI does not change the risk of cataract in the overall population.

Use of metformin and survival of patients with high-grade glioma.

High-grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population-based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox-regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81, HR for PFS = 0.29; 95% CI = 0.11-0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57-1.20) or PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression-free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin.

Parkinson disease and the risk of epileptic seizures.

OBJECTIVE: To assess the association between incident Parkinson disease (PD) and subsequent incident epileptic seizures. METHODS: We conducted a retrospective cohort study with a nested case-control analysis using data from the U.K. Clinical Practice Research Datalink. We identified patients aged ≥40 years with an incident diagnosis of PD between 1995 and 2016 and a matched comparison group of PD-free individuals. We calculated crude incidence rates (IRs) with 95% confidence intervals (CIs) of epileptic seizures in PD patients and the PD-free comparison group, and corresponding crude incidence rate ratios (IRRs). In the nested case-control analysis, we calculated adjusted odds ratios (adj. ORs) of incident PD among cases with incident epileptic seizures and seizure-free controls overall and stratified by various seizure-provoking comorbidities. RESULTS: Among 23,086 incident PD patients and 92,343 PD-free individuals, we identified 898 patients with incident epileptic seizures. The crude IR of epileptic seizures in PD patients was 266.7/100,000 person-years (95% CI = 235.6-297.7), and in PD-free individuals it was 112.4/100,000 person-years (95% CI = 103.5-121.3; IRR = 2.37, 95% CI = 2.06-2.73). The adj. OR of epileptic seizures was 1.68 (95% CI = 1.43-1.98) in PD patients compared with PD-free individuals. PD patients with comorbid brain disorders (adj. OR = 12.36, 95% CI = 8.74-17.48) or with > 1 seizure-provoking comorbidity (adj. OR = 13.24, 95% CI = 10.15-17.25) were at the highest risk of epileptic seizures compared with PD-free individuals with no seizure-provoking comorbidities. INTERPRETATION: This study suggests that incident PD is associated with an increased risk of incident epileptic seizures. Ann Neurol 2018;83:363-374.

Weight change and blood glucose concentration as markers for pancreatic cancer in subjects with new-onset diabetes mellitus: A matched case-control study.

OBJECTIVES: To evaluate the potential of blood glucose levels and weight change before the onset of diabetes as predictors of pancreatic cancer among subjects with new-onset diabetes, that is, cancer-related diabetes versus normal type 2 diabetes. METHODS: We conducted a case-control study among subjects with new diabetes in the United Kingdom-based Clinical Practice Research Datalink. Cases were pancreatic cancer subjects with diabetes for ≤2 years before the cancer diagnosis (i.e., cancer-related diabetes). Controls were cancer-free, type 2 diabetic subjects matched to cases on age, sex, and diabetes duration. We calculated adjusted odds ratios (aORs) for pancreatic cancer as a function of both weight change and blood glucose before the onset of diabetes. RESULTS: Weight loss of 10.0%-14.9% at diabetes onset was associated with an aOR for pancreatic cancer of 3.58 (95% CI 2.31-5.54), loss of ≥15.0%, with an aOR of 4.56 (95% CI 2.82-7.36), compared with stable weight. Blood glucose levels of ≤5.1 mmol/L or 5.2-5.6 mmol/L before diabetes onset were associated with an increased risk of a pancreatic cancer diagnosis, with aORs of 2.42 (95% CI 1.60-3.66) and 2.20 (95% CI 1.45-3.35), respectively, when compared with blood glucose levels ≥6.3 mmol/L within >2-3 years before cancer detection. CONCLUSIONS: Weight loss as well as blood glucose levels in the normal range (and thus rapid development of hyperglycemia) before diabetes onset may be predictive of pancreatic cancer-related diabetes and may help target which subjects with new diabetes to refer for pancreatic cancer screening examinations.

Evaluation of drug-related problems and subsequent clinical pharmacists' interventions at a Swiss university hospital.

WHAT IS KNOWN AND OBJECTIVE: The evaluation of clinical pharmacy services is essential for their further development and establishment. We analysed drug-related problems (DRPs) and subsequent clinical pharmacists' interventions (PIs) at a Swiss university hospital. METHOD: We conducted a retrospective analysis of DRPs and subsequent PIs that were identified and implemented during interdisciplinary ward rounds in internal medicine at the University Hospital Basel, Switzerland, between 2015 and 2017. We estimated the potential clinical and economic impact of PIs using a validated evaluation tool (CLEOde ). RESULTS AND DISCUSSION: Based on medication reviews of 5441 patients, clinical pharmacists identified 5024 DRPs, of which 2892 DRPs (57.6%) were followed by a PI that was directly accepted and implemented by the physician in charge and included in the present analysis. The leading cause and type of PIs were inappropriate dose and dose adjustment, respectively. Overall, 97.8% of DRPs were followed by PIs with an expected clinical benefit for the patients (major: 11.1%; moderate: 27.6%; minor: 59.1%). The drugs most often involved in PIs of major clinical impact were antithrombotics, acid blockers and cardiovascular drugs. With regard to the economic impact, 40.7% of DRPs implied PIs resulting in an increase of immediate therapy costs, whereas 39.3% implied PIs resulting in a decrease of immediate therapy costs. The remaining PIs were cost-neutral. WHAT IS NEW AND CONCLUSION: This study emphasizes that clinical pharmacists may help improve the effectiveness and safety of pharmacotherapy on acute care medical wards.

Injection testosterone and adverse cardiovascular events: A case-crossover analysis.

CONTEXT: Exogenous testosterone administration may affect blood clotting, polycythaemia, and may increase atherosclerosis, though any association with cardiovascular events is unclear. While the literature is inconclusive, some studies have suggested testosterone use may increase short-term risk of cardiovascular events and stroke, and injection testosterone may convey higher risks than other dosage forms. OBJECTIVE: We sought to evaluate the short-term cardiovascular risk of receiving injection testosterone. DESIGN: We conducted a case-crossover analysis comparing injection testosterone exposure in the 7 days prior to an outcome event to referent windows in the past to estimate the acute association of cardiovascular outcomes with the receipt of testosterone injections. PATIENTS: We identified adult male testosterone users hospitalized with myocardial infarction (MI), stroke or a composite of MI, stroke or unstable angina in US commercial claims (2000-2013) or Medicare (2007-2010) databases. MEASUREMENTS: We identified testosterone use for the patients from pharmacy dispensing claims or in-office procedure codes in the insurance billing data. RESULTS: We identified 2898 commercially insured men with events and recent testosterone use, and 339 from Medicare. Injected testosterone was associated with an increased risk of adverse events (composite outcome of myocardial infarction, stroke or unstable angina) in the immediate postinjection period for the older, Medicare population only: commercial insurance, odds ratios (OR) = 0.98 (95% confidence intervals [CI]: 0.86-1.12); Medicare, OR = 1.45 (1.07, 1.98). This association was either greatly attenuated or not present when evaluating receipt of any testosterone dosage forms (injection, gel, patch, implant): commercial insurance, OR = 1.01 (0.92, 1.11); Medicare, OR = 1.26 (95% CI: 0.98-1.63). CONCLUSIONS: Testosterone injections were uniquely associated with short-term risk of acute cardio- and cerebrovascular events in older adult men following injection receipt.

Adverse events profile of oral corticosteroids among asthma patients in the UK: cohort study with a nested case-control analysis.

BACKGROUND: To evaluate the adverse events profile of oral prednisolone among adult asthma patients in the UK. METHODS: Using data from the UK-based Clinical Practice Research Datalink, we conducted a series of cohort studies to quantify incidence rates and incidence rate ratios, and a series of nested case-control analyses to estimate crude and adjusted odds ratios, of 11 different potential corticosteroid-related adverse events (bone-related conditions, hypertension, peptic ulcer, severe infections, herpes zoster, diabetes mellitus type 2, cataract, glaucoma, chronic kidney disease, affective disorders, and cardiovascular events). RESULTS: Between 165,900 and 269,368 asthma patients were included in each of the 11 cohorts, of whom between 836 and 16,192 developed an outcome of interest. Incidence rates per 1000 person-years of potential corticosteroid-related adverse events in patients with new current use of oral prednisolone ranged from 1.4 (95% confidence interval [CI], 1.0-1.8) for peptic ulcer to 78.0 (95% CI, 74.8-81.2) for severe infections. After adjusting for confounding, current oral prednisolone use was most strongly associated with an increased risk of severe infection, compared with non-use of prednisolone; OR 2.16 (95% CI, 2.05-2.27). There were smaller elevated risks of peptic ulcer, affective disorders, and cataract at higher doses, and marginally increased risks of herpes zoster, cardiovascular events, diabetes mellitus type 2, and bone related conditions, compared with non-use of prednisolone. We did not observe an association between oral prednisolone use and glaucoma, chronic kidney disease, or hypertension. CONCLUSION: Oral prednisolone use is associated with infections, gastrointestinal, neuropsychiatric, ocular, cardiovascular, metabolic, and bone-related complications among adult asthma patients.

Selective Serotonin Reuptake Inhibitors and Cataract Risk: A Case-Control Analysis.

PURPOSE: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased cataract risk. We aimed to assess cataract risk after exposure to SSRI or to other antidepressant drugs in a large electronic primary care database. DESIGN: Case-control study. PARTICIPANTS: The study population was derived from the UK-based Clinical Practice Research Datalink (CPRD). We included patients with first-time cataract aged ≥40 years between 1995 and 2015 and an equal number of cataract-free controls matched on age, sex, general practice, date of cataract recording (i.e., index date), and years of history in the CPRD before the index date. METHODS: We conducted conditional logistic regression analyses adjusted for body mass index, smoking, hypertension, diabetes, and systemic steroid use. Exposure of interest was the number of SSRI prescriptions and prescriptions for other antidepressant drugs. We further explored mutually exclusive use of single SSRI substances. In sensitivity analyses, we shifted the index date backwards by 2 years, and we restricted our analyses to cases and controls without a prior glaucoma diagnosis. MAIN OUTCOME MEASURES: Relative risk estimates as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified 206 931 cataract cases and the same number of matched controls. Current long-term use of SSRI (≥20 prescriptions) was not associated with an increased cataract risk (adjusted OR, 0.99; 95% CI, 0.94-1.03). However, in a subset of patients aged 40 to 64 years, we found a slightly increased risk of cataract for long-term SSRI users (adjusted OR, 1.24; 95% CI, 1.15-1.34) compared with nonusers. CONCLUSIONS: In these data, use of SSRI was not associated with an increased risk of cataract. The slightly increased OR for individuals younger than 65 years of age in association with long-term SSRI use needs to be investigated in further studies.

The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs.

OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. METHODS: In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score. RESULTS: We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89-∞), phenytoin (OR 49.96, 95% CI 10.13-∞), and lamotrigine (OR 26.90, 95% CI 4.88-∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307). SIGNIFICANCE: The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.

Population-Based Study on the Epidemiology of Ménière's Disease.

BACKGROUND AND OBJECTIVE: Ménière's disease (MD) is a disorder of the inner ear typically showing recurrent acute episodes of vertigo, hearing loss, and tinnitus. Epidemiologic studies on MD are scarce. We assessed the incidence rates (IRs) of MD and describe the characteristics of MD cases, comparing them to control patients without recorded evidence of MD. STUDY DESIGN: We conducted a retrospective population-based follow-up study and a nested case-control analysis using data from the UK-based Clinical Practice Research Datalink. METHODS: We identified patients between 18 and 79 years of age with an incident MD diagnosis between January 1993 and December 2014. We assessed the IRs of betahistine-treated MD. In the nested case-control analysis, we matched 4 controls to each MD case on sex, age, general practice, years of active history in the database, and calendar time. We conducted a χ2 test to present p values in order to compare the prevalence of demographics, comorbidities, and co-medication between cases and controls. RESULTS: We identified 5,508 MD cases and 22,032 MD-free controls (65.4% females). The overall IR for MD in the UK was 13.1 per 100,000 person-years. More cases were female, and the mean age at diagnosis was 55.4 ± 13.7 years. Smoking and alcohol consumption were less prevalent among MD cases. Depression, other affective disorders, sleeping disorders, anxiety, and migraine were more prevalent among MD cases than among controls. CONCLUSIONS: MD is uncommon in primary care in the UK with a preponderance among females.

Validation of Stevens-Johnson syndrome or toxic epidermal necrolysis diagnoses in the Clinical Practice Research Datalink.

PURPOSE: To evaluate the validity of recorded diagnoses of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in the Clinical Practice Research Datalink (CPRD). METHODS: We identified patients with a diagnosis of SJS or TEN between 1995 and 2013 in the CPRD. We reviewed information from patient records, free text, and hospital episode statistics (HES) data, and excluded patients with no indication of a secondary care referral. Remaining patients were classified as probable, possible, or unlikely cases of SJS/TEN by two specialised clinicians or based on pre-defined classification criteria. We quantified positive predictive values (PPV) for all SJS/TEN patients and for patients categorised as 'probable/possible' cases of SJS/TEN, based on a representative subsample of 118 patients for whom we had unequivocal information (original discharge letters or HES data). RESULTS: We identified 1324 patients with a diagnosis of SJS/TEN, among whom 638 had a secondary care referral recorded. Of those, 565 were classified as probable or possible cases after expert review. We calculated a PPV of 0.79 (95% CI, 0.71-0.86) for all SJS/TEN patients with a recorded secondary care referral, and a PPV of 0.87 (95% CI, 0.81-0.93) for probable/possible cases. After excluding 14 false positive patients, our study population consisted of 551 SJS/TEN patients. CONCLUSIONS: Diagnoses of SJS/TEN are recorded with moderate diagnostic accuracy in the CPRD, which was substantially improved by additional expert review of all available information. We established a large population-based SJS/TEN study population of high diagnostic validity from the CPRD. Copyright © 2016 John Wiley & Sons, Ltd.

A combined intervention to reduce interruptions during medication preparation and double-checking: a pilot-study evaluating the impact of staff training and safety vests.

AIM: The aim was to evaluate the impact of staff training and wearing safety vests as a combined intervention on interruptions during medication preparation and double-checking. BACKGROUND: Interruptions and errors during the medication process are common and an important issue for patient safety in the hospital setting. METHODS: We performed a pre- and post-intervention pilot-study using direct structured observation of 26 nurses preparing and double-checking 431 medication doses (225 pre-intervention and 206 post-intervention) for 36 patients (21 pre-intervention and 15 post-intervention). RESULTS: With staff training and the introduction of safety vests, the interruption rate during medication preparation was reduced from 36.8 to 28.3 interruptions per hour and during double-checking from 27.5 to 15 interruptions per hour. CONCLUSION: This pilot-study showed that the frequency of interruptions decreased during the critical tasks of medication preparation and double-checking after the introduction of staff training and wearing safety vests as part of a quality improvement process. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing management should acknowledge interruptions as an important factor potentially influencing medication safety. Unnecessary interruptions can be successfully reduced by considering human and system factors and increasing both staff and nursing managers' awareness of 'interruptive communication practices' and implementing physical barriers. This is the first pilot-study specifically evaluating the impact of staff training and wearing safety vests on the reduction of interruptions during medication preparation and double-checking.

Influenza infections and risk of Alzheimer's disease.

Influenza may cause neuropsychiatric disorders, including confusion, delirium, convulsions, and encephalopathy. We conducted a case-control study to evaluate the association between diagnosed influenza and the risk of developing Alzheimer's disease (AD) using the UK-based Clinical Practice Research Datalink (CPRD). We identified 19,463 patients who developed an incident AD diagnosis between 1998 and 2013 and matched them 1:1 to dementia-free controls on age, sex, general practice, calendar time and number of years of recorded history. We calculated adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of developing AD in association with previous influenza infections and stratified by number of infections prior to the AD diagnosis date. Patients with a previous influenza infection were not at an increased risk of developing AD as compared to those with no previous infection (aOR, 95% CI 0.94, 0.87-1.02) overall. Nor was increasing number of infections related to an increased risk of developing AD; the aOR (95% CI) for those with 1, 2, or ⩾3 episodes was 0.98 (0.90-1.07), 0.70 (0.56-0.88), and 0.92 (0.63-1.34), respectively. Presence of an underlying chronic inflammatory disease in those with an influenza infection did not increase the risk of developing AD (aOR, 95% CI 0.83, 0.71-0.96), either, and there was no association between the severity of influenza infections (based on recorded neurological or bacterial complications) and the risk of AD. In conclusion, considering the limitations of this large observational study, we found no association between influenza infections and the risk of developing AD.