Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study

Background Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. Aims To describe initiation of psychotropic medication in the first year after partner bereavement. Methods In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. Results The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. Conclusion Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use

Prediction of first cardiovascular disease event in 2.9 million individuals using Danish administrative healthcare data:a nationwide, registry-based derivation and validation study

AIMS: The aim of this study was to derive and validate a risk prediction model with nationwide coverage to predict the individual and population-level risk of cardiovascular disease (CVD). METHODS AND RESULTS: All 2.98 million Danish residents aged 30–85 years free of CVD were included on 1 January 2014 and followed through 31 December 2018 using nationwide administrative healthcare registries. Model predictors and outcome were pre-specified. Predictors were age, sex, education, use of antithrombotic, blood pressure-lowering, glucose-lowering, or lipid-lowering drugs, and a smoking proxy of smoking-cessation drug use or chronic obstructive pulmonary disease. Outcome was 5-year risk of first CVD event, a combination of ischaemic heart disease, heart failure, peripheral artery disease, stroke, or cardiovascular death. Predictions were computed using cause-specific Cox regression models. The final model fitted in the full data was internally-externally validated in each Danish Region. The model was well-calibrated in all regions. Area under the receiver operating characteristic curve (AUC) and Brier scores ranged from 76.3% to 79.6% and 3.3 to 4.4. The model was superior to an age-sex benchmark model with differences in AUC and Brier scores ranging from 1.2% to 1.5% and −0.02 to −0.03. Average predicted risks in each Danish municipality ranged from 2.8% to 5.9%. Predicted risks for a 66-year old ranged from 2.6% to 25.3%. Personalized predicted risks across ages 30–85 were presented in an online calculator (https://hjerteforeningen.shinyapps.io/cvd-risk-manuscript/). CONCLUSION: A CVD risk prediction model based solely on nationwide administrative registry data provided accurate prediction of personal and population-level 5-year first CVD event risk in the Danish population. This may inform clinical and public health primary prevention efforts

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti- inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not influenced. Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve

Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer: A Nationwide Registry-Based Study.

Background: Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction. Objectives: The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio). Methods: Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed. Results: A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022). Conclusions: Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population

Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study

<p>Abstract</p> <p>Background</p> <p>The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI.</p> <p>Methods</p> <p>Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.</p> <p>Results</p> <p>The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).</p> <p>Conclusions</p> <p>We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.</p

Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia. METHODS: We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0), we linked the location of the arrest using the dispatch coordinates (longitude and latitude) to Victorian Local Government Areas (LGAs). We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates. RESULTS: Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1%) cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008-2010 to 68.6% in 2010-2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs. CONCLUSION: Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates

Cause for concern in the use of non-steroidal anti-inflammatory medications in the community -a population-based study

Background: Non-steroidal anti-inflammatory (NSAID) medications are a common cause of reported adverse drug side-effects. This study describes the prevalence of non-steroidal anti-inflammatory (NSAID) use (other than low-dose aspirin) and the presence of co-existing relative contraindications to NSAID use and chronic conditions in a representative population sample. Methods: Data were analysed from 3,206 adults attending first follow-up of the North West Adelaide Health Study (NWAHS) in 2004 - 2006, a longitudinal representative population study. Medications were brought into study clinic visits by participants. Clinical assessment included measured blood pressure, kidney function, serum cholesterol, blood glucose. Questionnaires assessed demographics, lifestyle risk factors, physician-diagnosed chronic conditions. Data were weighted to census measures by region, age group, gender, and probability of selection in the household, to provide population representative estimates. Pearson's Chi-square tests determined significant differences in proportions. Multiple logistic regression was used to examine associations of socio-demographic characteristics with use of NSAIDs. Results: Of 3,175 participants, 357 (11.2%), and 16% of those aged > 55 years, reported using either non-specific NSAIDs or COX-2 inhibitors, other than low-dose aspirin. Among people using NSAIDs, 60.8% had hypertension, 30.8% had Stage 3 or higher chronic kidney disease, 17.2% had a history of cardiovascular disease (CVD) and 20.7% had a > 15% 10-year CVD risk. The prevalence of NSAID use among people with hypertension was 16%, with kidney disease 15.9%, and a history of CVD 20.0%. Among people taking diuretics, 24.1% were also taking NSAIDs, and of those taking medications for gastro-esophageal reflux, 24.7% were on NSAIDs. Prescription-only COX-2 inhibitors, but not other NSAIDs, were used more by people > 75 years than by 35-54 year olds (OR 3.7, 95% CI 2.0, 6.7), and also were more commonly used by people with hypertension, cardiac and kidney disease. Conclusions: There is a high prevalence of current NSAID use among groups at-risk for significant drug-related adverse events or who have major chronic conditions that are relative contraindications to NSAID use. Assessment of absolute risks regarding cardiovascular and kidney disease need to take into account use of medications such as NSAIDs. The potential to make a substantial impact on chronic disease burden via improved use of NSAIDs is considerable.Robert J Adams, Sarah L Appleton, Tiffany K Gill, Anne W Taylor, David H Wilson and Catherine L Hil