Objective: To estimate the risk of hand osteoarthritis (HOA) associated with hormone replacement therapy (HRT). Methods: We conducted a nested case-control study using data from the UK-based Clinical Practice Research Datalink (1998-2017). In women entering at age 45 (inception cohort), we matched women with incident HOA during follow-up (cases) 1:4 to osteoarthritis-free controls on age and calendar date (index date, ID). We applied conditional logistic regression to calculate odds ratios (OR) with 95% confidence intervals (CI) of HOA associated with new HRT use compared to non-use overall and in women with recorded menopause, in whom, we calculated separate ORs subdivided by time between menopause and HRT initiation (current users), and by time between HRT cessation and the ID (past users), versus non-users. Results: Among 3440 cases and 13,760 controls (mean age: 50.9±4.1 years), we observed an adjusted OR (aOR) of HOA of 1.32 (95% CI 1.17-1.48) in HRT users (versus non-users), which attenuated to 0.98 (95% CI 0.85-1.14) in women with recorded menopause. Current users (versus non-users), who initiated HRT within 3 months before/after menopause, had an aOR of 0.72 (95% CI 0.55-0.96), while aORs increased with later HRT initiation. Among past users (versus non-users), we observed an aOR of 1.25 (95% CI 0.86-1.81) when HRT use was stopped ≤18 months before the ID, approaching the null with increasing duration between HRT cessation and the ID. Conclusion: Current HRT use was associated with a decreased risk of HOA if initiated around menopause, but the risk reduction disappeared after HRT cessation.

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 (2014–2018). 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] 33.9–35.0%) of pregnancies, most frequently paracetamol (30.3%, 29.8–30.8%), followed by NSAIDs (8.6%, 8.3–8.8%), and opioids (2.6%, 2.4–2.8%). NSAIDs were claimed in 1.3% (1.2–1.4%) of pregnancies after week 24, and opioids were claimed in 1.3% (1.2–1.4%) in trimester 3. Antibiotics were dispensed in 26.3% (25.8–26.8%) of pregnancies, most frequently amoxicillin (14.6%, 95% CI 14.2–14.9%). Claims for potentially teratogenic or fetotoxic antibiotics during risk periods were each recorded in <0.6% of pregnancies. PPIs were claimed in 16.0% (15.6–16.3%) and antacids in 10.6% (10.3–11.0%) of pregnancies, but several antacid products are not reimbursed and thus not present in insurance claims. Anti-nausea drugs were claimed in 16.4% (16.0–16.7%) of pregnancies, most frequently metoclopramide in 14.4% (14.0–14.7%). Ondansetron was mainly dispensed in trimester 1, 1.0% (0.9–1.1%). In total, 6.4% (6.2–6.7%) of pregnancies had a claim for laxatives, most frequently for macrogol (2.4%, 95% CI 2.2–2.5%). 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.

AIMS OF THE STUDY: The prevalence of the use of valproate during pregnancy and by women of childbearing age in Switzerland is not known. We aimed to study the use of antiseizure drugs by these women in Switzerland, with a particular focus on valproate. METHODS:We conducted a retrospective descriptive study using the healthcare claims database of the Swiss health insurance Helsana (2014-18). We established two separate study populations: (1) a cohort of pregnancies leading to a delivery, and (2) all women of childbearing age (15-45 years) who were insured with Helsana for at least one year during the study period. We identified the dispensation of valproate, lamotrigine, carbamazepine, levetiracetam, topiramate, pregabalin, gabapentin, phenobarbital, and phenytoin (1) between delivery and three months prior to the estimated date of the last menstrual period, and (2) by calendar year. We quantified exposure prevalence of each antiseizure drug as the number of women with ≥1 prescription fill per 10,000 (1) pregnancies, and (2) women by calendar year. Results were weighted for the demographic distribution of the Helsana population relative to the Swiss population.RESULTS: We identified a weighted pregnancy population of 387,418 pregnancies, with a mean maternal age at delivery of 31.9 years (standard deviation 5.1). Lamotrigine was the most frequently dispensed antiseizure drug during pregnancy (20/10,000), followed by levetiracetam (11/ 10,000), and pregabalin (3.8/10,000). Valproate was dispensed to 1.9/10,000 women during pregnancy and to 1.3/ 10,000 women within 90 days prior to the last menstru-al period but not during pregnancy. The weighted study population of women aged 15-45 years consisted of 2,781,151 women, of whom 74,080 (270/10,000) were exposed to ≥1 of the evaluated antiseizure drugs. Pregabalin was the most frequently dispensed antiseizure drug (64/ 10,000), followed by lamotrigine (46/10,000), topiramate (32/10,000), and valproate (25/10,000). The use of valproate decreased from 28/10,000 women in 2014 to 21/ 10,000 women in 2018. CONCLUSIONS:The prevalence of exposure to valproate during pregnancy was comparable to Denmark and lower than in other European countries. Despite decreasing exposure prevalence, the use of valproate in women of childbearing age in Switzerland seems higher than the actual clinical need.