Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Use of unlicensed drugs in a Swiss Pediatric University Hospital and associated prescribing error rates - a retrospective observational study.

AIMS OF THE STUDY: Unlicensed drugs are frequently used in paediatric care. To what extent they are prescribed in hospital care in Switzerland is unclear. Because prescribing errors seem to occur more frequently with unlicensed drugs, we aimed to assess the prevalence of unlicensed drug prescriptions in two study periods (2018 and 2019) at the University Children's Hospital Zurich, compare these periods and investigate whether unlicensed drugs were more prone to prescribing errors than licensed drugs. METHODS: We conducted a sub-analysis of a retrospective single-centre observational study and analysed 5,022 prescriptions for a total of 1,000 patients from 2018 and 2019 in paediatric general wards. The rate of unlicensed drugs, consisting of imported or formula drugs, was investigated. The prescriptions from 2019 were further analysed on prescribing errors to see whether errors occurred more often in unlicensed or licensed drug use. RESULTS: Of all prescriptions, 10.8% were unlicensed drugs, with around half each being imported and formula drugs. Among all patients, 34% were prescribed at least one unlicensed drug. Younger paediatric patients were prescribed more unlicensed drugs than older paediatric patients (newborns: 15.8% of prescriptions, infants: 13.4%, children: 10.6%, adolescents: 7.1%). Ibuprofen suppositories, midazolam oral solution and gentamicin i.v. solution were the most frequently prescribed imported drugs. Macrogol powder, lisinopril oral suspension and potassium chloride i.v. solution were the most frequently prescribed formula drugs. The most common drug forms in unlicensed use were oral liquid forms and i.v. SOLUTIONS: Unlicensed drugs had a significantly higher rate of prescribing errors than licensed drugs (31.6 errors per 100 prescriptions [95% CI: 26.1-37.0] versus 24.3 errors per 100 prescriptions [95% CI: 22.3-26.2], p = 0.024). In particular, formula drugs carried a higher risk (36.4 errors per 100 prescriptions, p = 0.012). CONCLUSIONS: Unlicensed drugs are frequently prescribed in this paediatric hospital setting in Switzerland. Around every tenth prescription is an unlicensed drug. Because unlicensed drugs showed a significantly higher rate of prescribing errors, licensed drugs are favourable in terms of medication safety and should be prescribed whenever possible. If no licensed drug is available, imported drugs should be favoured over formula drugs due to lower prescribing error rates. To increase medication safety in paediatrics in Switzerland, efforts are necessary to increase the number of suitable licensed drug formulations for paediatric patients, including developing new innovative drug formulations for children.

Assessing prescription of antibiotics after vaccination against pneumococcal pneumonia; using prescription sequence symmetry analysis.

OBJECTIVES: Prescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients. METHODS: We studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs. RESULTS: Amoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705-0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658-0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls. DISCUSSION: The lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption.

Prescribing Patterns in Pediatric General Wards and Their Association with Prescribing Errors: A Retrospective Observational Study.

PURPOSE: There are only limited data on drug utilization patterns in pediatric inpatients, especially on general wards. The aim of the study was to describe prescribing patterns and their associations with prescribing errors in a university children's hospital in the German-speaking part of Switzerland. METHOD: This was a subanalysis of a retrospective single-center observational study. Patient characteristics and drug use of 489 patients with 2693 drug prescriptions were associated with prescribing errors. Drugs were categorized by the Anatomic Therapeutic Chemical Classification System (ATC), patients were categorized by age group according to European Medicines Agency guidelines, and prescribing errors were analyzed by type [Pharmaceutical Care Network Europe (PCNE) classification] and severity of error [adapted National Coordinating Council for Medication Error Reporting (NCC MERP) index]. RESULTS: The most frequently prescribed ATC classes were nervous system (N) (42.6%), alimentary system (A) (15.6%), and anti-infective drugs (J) (10.7%). Eighty-two percent of patients were prescribed an analgesic. Most drugs were prescribed for oral (47%) or intravenous (32%) administration, but the rectal route was also frequent (10%). The most frequently prescribed drugs were paracetamol, metamizole, and ibuprofen. The high number of metamizole prescriptions (37% of patients were prescribed metamizole) is typical for German-speaking countries. Older pediatric patients were prescribed more drugs than younger patients. A statistically significant difference was found in the rate of potentially harmful errors across age groups and for gender; children between 2 and 11 years had a higher rate of potentially harmful errors than infants under 2 years (p = 0.029) and female patients had a higher rate of potentially harmful errors than male patients (p = 0.023). Recurring errors were encountered with certain drugs (nalbuphine, cefazolin). CONCLUSIONS: Our study provides insight into prescribing patterns on pediatric general wards in a university children's hospital in Switzerland and highlights some areas for future research. Especially, the higher risk for prescribing errors among female pediatric patients needs further investigation.

Assessing the Risk of Developing Delirium on Admission to Inpatient Rehabilitation: A Clinical Prediction Model.

OBJECTIVES: To develop a clinical model to predict the risk of an individual patient developing delirium during inpatient rehabilitation, based on patient characteristics and clinical data available on admission. DESIGN: Retrospective observational study based on electronic health record data. SETTING AND PARTICIPANTS: We studied a previously validated data set of inpatients including incident delirium episodes during rehabilitation. These patients were admitted to ZURZACH Care, Rehaklinik Bad Zurzach, a Swiss inpatient rehabilitation clinic, between January 1, 2015, and December 31, 2018. METHODS: We performed logistic regression analysis using backward and forward selection with alpha = 0.01 to remove any noninformative potential predictor. We subsequentially used the Akaike information criterion (AIC) to select the final model among the resulting "intermediate" models. Discrimination of the final prediction model was evaluated using the C-statistic. RESULTS: Of the 20 candidate predictor variables, 6 were included in the final prediction model: a linear spline of age with 1 knot at 60 years and a linear spline of the functional independence measure (FIM), a measure of the functional degree of patients independency, with 1 knot at 64 points, diagnosis of disorders of fluid, electrolyte, and acid-base balance (E87), use of other analgesic and antipyretics (N02B), use of anti-parkinson drugs (N04B), and an anticholinergic burden score (ACB) of ≥3 points. CONCLUSIONS AND IMPLICATIONS: Our clinical prediction model could, upon validation, identify patients at risk of incident delirium at admission to inpatient rehabilitation, and thus enable targeted prevention strategies.

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.

Potential Risk Factors for, and Clinical Implications of, Delirium during Inpatient Rehabilitation: A Matched Case-Control Study.

OBJECTIVES: To investigate the association between a wide set of baseline characteristics (age, sex, rehabilitation discipline), functional scores [Functional Independence Measure (FIM), cumulative Illness Rating Scale (CIRS)], diseases, and administered drugs and incident delirium in rehabilitation inpatients and, furthermore, to assess clinical implications of developing delirium during rehabilitation. DESIGN: Matched case-control study based on electronic health record data. SETTING AND PARTICIPANTS: We studied rehabilitation stays of inpatients admitted between January 1, 2015, and December 31, 2018, to ZURZACH Care, Rehaklinik Bad Zurzach, an inpatient rehabilitation clinic in Switzerland. METHODS: We conducted unconditional logistic regression analyses to estimate adjusted odds ratios (AORs) with 95% CIs of exposures that were recorded in ≥5 cases and controls. RESULTS: Among a total of 10,503 rehabilitation stays, we identified 125 validated cases. Older age, undergoing neurologic rehabilitation, a low FIM, and a high CIRS were associated with an increased risk of incident delirium. Being diagnosed with a bacterial infection (AOR 2.62, 95% CI 1.06-6.49), a disorder of fluid, electrolyte, or acid-base balance (AOR 2.76, 95% CI 1.19-6.38), Parkinson's disease (AOR 5.68, 95% CI 2.54-12.68), and administration of antipsychotic drugs (AOR 8.06, 95% CI 4.26-15.22), antiparkinson drugs (AOR 2.86, 95% CI 1.42-5.77), drugs for constipation (AOR 2.11, 95% CI 1.25-3.58), heparins (AOR 2.04, 95% CI 1.29-3.24), or antidepressant drugs (AOR 1.88, 95% CI 1.14-3.10) during rehabilitation, or an increased anticholinergic burden (ACB ≥ 3) (AOR 2.59, 95% CI 1.41-4.73) were also associated with an increased risk of incident delirium. CONCLUSIONS AND IMPLICATIONS: We identified a set of factors associated with an increased risk of incident delirium during inpatient rehabilitation. Our findings contribute to detect patients at risk of delirium during inpatient rehabilitation.

Pharmacists' clinical roles and activities in inpatient hospice and palliative care: a scoping review.

BACKGROUND: Pharmacists contribute to medication safety by providing their services in various settings. However, standardized definitions of the role of pharmacists in hospice and palliative care (HPC) are lacking. AIM: The purpose of this scoping review was to provide an overview of the evidence on the role of pharmacists and to map clinical activities in inpatient HPC. METHOD: We performed a scoping review according to the PRISMA-ScR extension in CINAHL, Embase, and PubMed. We used the American Society of Hospital Pharmacists (ASHP) Guidelines on the Pharmacist's Role in Palliative and Hospice Care as a framework for standardized categorization of the identified roles and clinical activities. RESULTS: After screening 635 records (published after January 1st, 2000), the scoping review yielded 23 publications reporting various pharmacy services in HPC. The articles addressed the five main categories in the following descending order: 'Medication order review and reconciliation', 'Medication counseling, education and training', 'Administrative Roles', 'Direct patient care', and 'Education and scholarship'. A total of 172 entries were mapped to the subcategories that were added to the main categories. CONCLUSION: This scoping review identified a variety of pharmacists' roles and clinical activities. The gathered evidence will help to establish and define the role of pharmacists in inpatient hospice and palliative care.

Prescription Trends in Hospice Care: A Longitudinal Retrospective and Descriptive Medication Analysis.

BACKGROUND: In hospice and palliative care, drug therapy is essential for symptom control. However, drug regimens are complex and prone to drug-related problems. Drug regimens must be simplified to improve quality of life and reduce risks associated with drug-related problems, particularly at end-of-life. To support clinical guidance towards a safe and effective drug therapy in hospice care, it is important to understand prescription trends. OBJECTIVES: To explore prescription trends and describe changes to drug regimens in inpatient hospice care. DESIGN: We performed a retrospective longitudinal and descriptive analysis of prescriptions for regular and as-needed (PRN) medication at three timepoints in deceased patients of one Swiss hospice. SETTING/SUBJECTS: Prescription records of all patients (≥ 18 years) with an inpatient stay of three days and longer (admission and time of death in 2020) were considered eligible for inclusion. RESULTS: Prescription records of 58 inpatients (average age 71.7 ± 12.8 [37-95] years) were analyzed. The medication analysis showed that polypharmacy prevalence decreased from 74.1% at admission to 13.8% on the day of death. For regular medication, overall numbers of prescriptions decreased over the patient stay while PRN medication decreased after the first consultation by the attending physician and increased slightly towards death. CONCLUSIONS: Prescription records at admission revealed high initial rates of polypharmacy that were reduced steadily until time of death. These findings emphasize the importance of deprescribing at end-of-life and suggest pursuing further research on the contribution of clinical guidance towards optimizing drug therapy and deprescribing in inpatient hospice care.

Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database.

Purpose: In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland. Methods: We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana). Results: Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes (CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MT-RNR1, and VKORC1) were responsible for over 95% of all potential drug-gene interactions. Conclusion: The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit.

Recording of Chronic Diseases and Adverse Obstetric Outcomes during Hospitalizations for a Delivery in the National Swiss Hospital Medical Statistics Dataset between 2012 and 2018: An Observational Cross-Sectional Study.

The prevalence of chronic diseases during pregnancy and adverse maternal obstetric outcomes in Switzerland has been insufficiently studied. Data sources, which reliably capture these events, are scarce. We conducted a nationwide observational cross-sectional study (2012−2018) using data from the Swiss Hospital Medical Statistics (MS) dataset. To quantify the recording of chronic diseases and adverse maternal obstetric outcomes during delivery in hospitals or birthing centers (delivery hospitalization), we identified women who delivered a singleton live-born infant. We quantified the prevalence of 23 maternal chronic diseases (ICD-10-GM) and compared results to a nationwide Danish registry study. We further quantified the prevalence of adverse maternal obstetric outcomes (ICD-10-GM/CHOP) during the delivery hospitalization and compared the results to existing literature from Western Europe. We identified 577,220 delivery hospitalizations, of which 4.99% had a record for ≥1 diagnosis of a chronic disease (versus 15.49% in Denmark). Moreover, 13 of 23 chronic diseases seemed to be substantially under-recorded (8 of those were >10-fold more frequent in the Danish study). The prevalence of three of the chronic diseases was similar in the two studies. The prevalence of adverse maternal obstetric outcomes was comparable to other European countries. Our results suggest that chronic diseases are under-recorded during delivery hospitalizations in the MS dataset, which may be due to specific coding guidelines and aspects regarding whether a disease generates billable effort for a hospital. Adverse maternal obstetric outcomes seemed to be more completely captured.

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.

Use of Prescribed Drugs to Treat Chronic Diseases during Pregnancy in Outpatient Care in Switzerland between 2014 and 2018: Descriptive Analysis of Swiss Health Care Claims Data.

Evidence on the use of drugs during pregnancy in Switzerland is lacking. We aimed to evaluate the utilisation of drugs to treat chronic diseases during pregnancy in Switzerland. We identified all pregnancies (excluding abortions) in Swiss Helsana claims data (2014-2018). In those, we identified all claims for drugs to treat a chronic disease, which typically affects women of childbearing age. Potentially teratogenic/fetotoxic drugs were evaluated during specific risk periods. Results were demographically weighted relative to the Swiss population. We identified claims for ≥1 drug of interest during 22% of 369,371 weighted pregnancies. Levothyroxine was most frequently claimed (6.6%). Antihypertensives were claimed during 5.3% (3.9% nifedipine in T3). Renin-Angiotensin-Aldosterone System (RAAS) inhibitors were dispensed to 0.3/10,000 pregnancies during trimester 2 (T2) or trimester 3 (T3). Insulin was claimed during 3.5% of pregnancies, most frequently in T3 (3.3%). Exposure to psychotropic drugs was 3.8% (mostly Selective serotonin reuptake inhibitors (SSRIs)) and to drugs for obstructive airway diseases 3.6%. Traditional immunosuppressants (excluding corticosteroids) were claimed during 0.5% (mainly azathioprine and hydroxychloroquine), biologic immunosuppressants (Tumour necrosis factor-alpha (TNF-alpha) inhibitors and interleukin inhibitors) during 0.2%, and drugs to treat multiple sclerosis during 0.09% of pregnancies. Antiretrovirals were claimed during 0.15% of pregnancies. Patterns of drug claims were in line with treatment recommendations, but relatively rare events of in utero exposure to teratogenic drugs may have had severe implications for those involved.

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.

ß-Blockers and the Risk of Depression: A Matched Case-Control Study.

INTRODUCTION: Depression is a commonly cited adverse effect of ß-blockers but the evidence for a causal relationship is limited. OBJECTIVE: We aimed to explore whether ß-blockers are associated with an increased risk of new-onset depression. METHODS: We conducted a case-control study using the UK population-based Clinical Practice Research Datalink (CPRD) GOLD. We identified patients aged 18-80 years with an incident depression diagnosis between 2000 and 2016, and matched controls, and estimated the risk (odds ratio [OR]) of depression in association with use of ß-blockers. We also conducted analyses of exposure, categorised by number and timing of prescriptions and by indication for ß-blocker use. RESULTS: The study encompassed 118,705 patients with incident depression and the same number of matched controls. The odds of developing depression were increased for current short-term use of any ß-blocker (adjusted OR [aOR] 1.91, 95% confidence interval [CI] 1.72-2.12), whereas current long-term use was not associated with the risk of depression compared with never use. The elevated risk of depression among short-term users was mostly confined to propranolol users with a neuropsychiatric disorder (aOR 6.33, 95% CI 5.16-7.76), while propranolol users with a cardiovascular indication were only at marginally increased risk of depression (aOR 1.44, 95% CI 1.14-1.82). CONCLUSIONS: This study suggests that the association between use of ß-blockers and depression may not be causal but rather a result of protopathic bias. Propranolol is often prescribed to treat neuropsychiatric symptoms, suggesting that the onset of depression may be related to the underlying indication rather than to an effect of a ß-blocker therapy.

Detecting Incident Delirium within Routinely Collected Inpatient Rehabilitation Data: Validation of a Chart-Based Method.

BACKGROUND: Delirium is a brain condition associated with poor outcomes in rehabilitation. It is therefore important to assess delirium incidence in rehabilitation. PURPOSE: To develop and validate a chart-based method to identify incident delirium episodes within the electronic database of a Swiss rehabilitation clinic, and to identify a study population of validated incident delirium episodes for further research purposes. DESIGN: Retrospective validation study. SETTINGS: Routinely collected inpatient clinical data from ZURZACH Care. PARTICIPANTS: All patients undergoing rehabilitation at ZURZACH Care, Rehaklinik Bad Zurzach between 2015 and 2018 were included. METHODS: Within the study population, we identified all rehabilitation stays for which ≥2 delirium-predictive key words (common terms used to describe delirious patients) were recorded in the medical charts. We excluded all prevalent delirium episodes and defined the remaining episodes to be potentially incident. At least two physicians independently confirmed or refuted each potential incident delirium episode by reviewing the patient charts. We calculated the positive predictive value (PPV) with 95% confidence interval (95% CI) for all potential incident delirium episodes and for specific subgroups. RESULTS: Within 10,515 rehabilitation stays we identified 554 potential incident delirium episodes. Overall, 125 potential incident delirium episodes were confirmed by expert review. The PPV of the chart-based method varied from 0.23 (95% CI 0.19-0.26) overall to 0.69 (95% CI 0.56-0.79) in specific subgroups. CONCLUSIONS: Our chart-based method was able to capture incident delirium episodes with low to moderate accuracy. By conducting an additional expert review of the medical charts, we identified a study population of validated incident delirium episodes. Our chart-based method contributes towards an automated detection of potential incident delirium episodes that, supplemented with expert review, efficiently yields a validated population of incident delirium episodes for research purposes.

Use of drugs to treat symptoms and acute conditions during pregnancy in outpatient care in Switzerland between 2014 and 2018: analysis of Swiss healthcare claims data.

BACKGROUND: Evidence on the use of drugs during pregnancy in Switzerland is lacking. OBJECTIVES: To evaluate utilisation of prescribed drugs during pregnancy in outpatient care in Switzerland, focusing on treatments for pain, infections, gastro-oesophageal reflux, nausea/vomiting, and constipation. METHODS: We conducted a descriptive study using the Swiss Helsana claims database (2014­2018). We established a cohort of pregnancies by identifying deliveries and estimating the date of the last menstrual period. We identified claims for the following drugs during pregnancy; analgesics (opioids, paracetamol, and nonsteroidal anti-inflammatory drugs [NSAIDs]), oral antibiotics, antacids, proton pump inhibitors (PPIs), anti-nausea drugs (propulsives and 5HT3-antagonists), and laxatives. Within these drug groups we quantified exposure prevalence to the most prescribed drugs (to >1% of pregnancies) during pregnancy as well as to specific potentially teratogenic or fetotoxic drugs during specific risk periods. Results were extrapolated relative to the demographic distribution of the Swiss population. RESULTS: We identified an extrapolated population of 369,371 pregnancies, with a weighted mean maternal age of 32.0 years (weighted standard deviation 5.1). Analgesics were claimed in 34.5% (95% confidence interval [CI] 33.9­35.0%) of pregnancies, most frequently paracetamol (30.3%, 29.8­30.8%), followed by NSAIDs (8.6%, 8.3­8.8%), and opioids (2.6%, 2.4­2.8%). NSAIDs were claimed in 1.3% (1.2­1.4%) of pregnancies after week 24, and opioids were claimed in 1.3% (1.2­1.4%) in trimester 3. Antibiotics were dispensed in 26.3% (25.8­26.8%) of pregnancies, most frequently amoxicillin (14.6%, 95% CI 14.2­14.9%). Claims for potentially teratogenic or fetotoxic antibiotics during risk periods were each recorded in <0.6% of pregnancies. PPIs were claimed in 16.0% (15.6­16.3%) and antacids in 10.6% (10.3­11.0%) of pregnancies, but several antacid products are not reimbursed and thus not present in insurance claims. Anti-nausea drugs were claimed in 16.4% (16.0­16.7%) of pregnancies, most frequently metoclopramide in 14.4% (14.0­14.7%). Ondansetron was mainly dispensed in trimester 1, 1.0% (0.9­1.1%). In total, 6.4% (6.2­6.7%) of pregnancies had a claim for laxatives, most frequently for macrogol (2.4%, 95% CI 2.2­2.5%). CONCLUSION: The observed pattern of claimed drugs during pregnancy is in line with existing treatment guidelines. Exposure to potentially teratogenic and fetotoxic drugs was small, but given the lack of recorded diagnosis, we cannot determine if their use was clinically indicated.

Utilisation patterns and costs of lipid-lowering drugs in Switzerland 2013-2019.

OBJECTIVE: To analyse utilisation patterns of lipid-lowering drugs and the related costs in Switzerland between the years 2013 and 2019. METHODS: We conducted a retrospective descriptive study using administrative claims data of persons aged ≥18 years enrolled with the health insurance company Helsana. To enable statements at the Swiss population level, results were extrapolated according to age, sex and canton of residence. RESULTS: The overall prevalence of patients taking lipid-lowering drugs rose from 8.9% (n = 736,174) in 2013 to 11.6% (n = 841,682) in 2019, but varied markedly across regions, with highest values in Ticino and lowest values in Zurich. More than every third individual aged ≥65 years was treated with a lipid-lowering drug in 2019. Statins were by far the most commonly used drugs (>90% of prescriptions), followed by ezetimibe, fibrates and PCSK9 inhibitors. We observed a trend towards the prescription of more potent statins (atorvastatin, rosuvastatin) in recent years. Total costs of lipid-lowering drugs increased from CHF 222 million in 2013 to CHF 230 million in 2019 (+3.5%), whereas annual per capita costs decreased from CHF 302 in 2013 to CHF 273 in 2019 (-9.4%). CONCLUSION: The increasing use of lipid-lowering drugs reflects current therapeutic guidelines, but results in high costs for the healthcare system.

A review of the evidence on the risk of congenital malformations and neurodevelopmental disorders in association with antiseizure medications during pregnancy.

Introduction: The majority of women with epilepsy require treatment with antiseizure medications (ASM) throughout pregnancy. However, in utero exposure to several ASM has been associated with an increased risk of congenital malformations and/or neurodevelopmental disorders (CM/NDD) in the child, but observational evidence is methodologically heterogeneous.Areas covered: We critically evaluate current evidence on the risk of CM/NDD in children of women with epilepsy after in utero exposure to different ASM. We highlight characteristics of different data sources and discuss their benefits and drawbacks. This review includes evidence published before December 2020.Expert opinion: Given the lack of randomized controlled trials, evidence on in utero safety of ASM originates from methodologically heterogeneous post-marketing observational studies based on registries, prospective cohorts, and large electronic health databases. It has been clearly demonstrated that valproate is associated with a high risk of CM/NDD, whereas lamotrigine and levetiracetam are relatively safe. However, evidence is less explicit for other ASM. Reported risks vary depending on the size and origin of the underlying study population, the definition of exposure and outcomes, and other aspects of the study design. Increased collaboration between data sources to increase sample size is desirable.

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.