Trends in polypharmacy and potentially inappropriate medication (PIM) in older and middle-aged people treated for diabetes.

AIMS: Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle-aged people with diabetes. METHODS: A repeated cross-sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012-2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria for 45-64 years old. Chi-square tests and regression analysis were applied. RESULTS: The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45-54 years, 50.3% in those aged 55-64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle-aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long-term high-dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. CONCLUSIONS: Polypharmacy increased in older and middle-aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle-aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age.

Prescribing of Antidiabetic Medicines before, during and after Pregnancy: A Study in Seven European Regions.

AIM: To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe. METHODS: A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women with a pregnancy starting and ending between 2004 and 2010, (Denmark, 2004-2009; Norway, 2005-2010; Emilia Romagna, 2008-2010), which ended in a live or stillbirth, were identified. Prescriptions for antidiabetic medicines issued (UK) or dispensed (non-UK) during pregnancy and/or the year before or year after pregnancy were identified. Prescribing patterns were compared across databases and over calendar time. RESULTS: 1,082,673 live/stillbirths were identified. Pregestational insulin prescribing during the year before pregnancy ranged from 0.27% (CI95 0.25-0.30) in Tuscany to 0.45% (CI95 0.43-0.47) in Norway, and increased between 2004 and 2009 in all countries. During pregnancy, insulin prescribing peaked during the third trimester and increased over time; third trimester prescribing was highest in Tuscany (2.2%) and lowest in Denmark (0.5%). Of those prescribed an insulin during pregnancy, between 50.5% in Denmark and 88.8% in the Netherlands received an insulin analogue alone or in combination with human insulin, this proportion increasing over time. Oral products were mainly metformin and prescribing was highest in the 3 months before pregnancy. Metformin use during pregnancy increased in some countries. CONCLUSION: Pregestational diabetes is increasing in many areas of Europe. There is considerable variation between and within countries in the choice of medication for treating pregestational diabetes in pregnancy, including choice of insulin analogues and oral antidiabetics, and very large variation in the treatment of gestational diabetes despite international guidelines.

Asthma medication prescribing before, during and after pregnancy: a study in seven European regions.

OBJECTIVES: To explore utilisation patterns of asthma medication before, during and after pregnancy as recorded in seven European population-based databases. DESIGN: A descriptive drug utilisation study. SETTING: 7 electronic healthcare databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna and Tuscany), Wales, and the Clinical Practice Research Datalink representing the rest of the UK. PARTICIPANTS: All women with a pregnancy ending in a delivery that started and ended between 2004 and 2010, who had been present in the database for the year before, throughout and the year following pregnancy. MAIN OUTCOME MEASURES: The percentage of deliveries where the woman received an asthma medicine prescription, based on prescriptions issued (UK) or dispensed (non-UK), during the year before, throughout or during the year following pregnancy. Asthma medicine prescribing patterns were described for 3-month time periods and the choice of asthma medicine and changes in prescribing over the study period were evaluated in each database. RESULTS: In total, 1,165,435 deliveries were identified. The prevalence of asthma medication prescribing during pregnancy was highest in the UK and Wales databases (9.4% (CI95 9.3% to 9.6%) and 9.4% (CI95 9.1% to 9.6%), respectively) and lowest in the Norwegian database (3.7% (CI95 3.7% to 3.8%)). In the year before pregnancy, the prevalence of asthma medication prescribing remained constant in all regions. Prescribing levels peaked during the second trimester of pregnancy and were at their lowest during the 3-month period following delivery. A decline was observed, in all regions except the UK, in the prescribing of long-acting ß-2-agonists during pregnancy. During the 7-year study period, there were only small changes in prescribing patterns. CONCLUSIONS: Differences were found in the prevalence of prescribing of asthma medications during and surrounding pregnancy in Europe. Inhaled ß-2 agonists and inhaled corticosteroids were, however, the most popular therapeutic regimens in all databases.

Maternal high-dose folic acid during pregnancy and asthma medication in the offspring.

PURPOSE: Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to investigate the effect of dispensed high-dose folic acid during pregnancy and asthma medication in the offspring. METHODS: We used data from the pregnancy database IADB.nl, which contains pharmacy-dispensing data of mothers and children from community pharmacies in the Netherlands from 1994 until 2011. The dispension of asthma medication in children exposed in utero to high-dose folic acid was compared with children who were not exposed to this high dose. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated. RESULTS: In 2.9% (N = 913) of the 39,602 pregnancies in the database, the mother was dispensed high-dose folic acid. Maternal high-dose folic acid was associated with an increased rate of asthma medication among children: recurrent asthma medication IRR = 1.14 (95%CI: 1.04-1.30) and recurrent inhaled corticosteroids IRR = 1.26 (95%CI: 1.07-1.47). Associations were clustered on the mother and adjusted for maternal age, maternal asthma medication, and dispension of benzodiazepines during pregnancy. CONCLUSION: Almost 3% of the children were prenatally exposed to high-dose folic acid. This study suggests that supplementation of high-dose folic acid during pregnancy might increase the risk of childhood asthma.

Antibiotics prescribed before, during and after pregnancy in the Netherlands: a drug utilization study.

PURPOSE: To describe the prescription of antibiotics before, during and after pregnancy, and the trends over a 16-year period in the Netherlands, and to determine whether they were prescribed according to national guidelines. METHODS: The IADB (http://iadb.nl) contains prescriptions dispensed by community pharmacies in the Netherlands. We extracted information on 18,873 pregnancies for 14,969 women between 1994 and 2009, focusing on antibiotics dispensed in the four trimesters before conception to two trimesters after birth (nine trimesters in total). We calculated trends in prescription rates during pregnancy and over time, and also compared the prescription of antibiotics in the Netherlands with safety category based on the Australian Drug Evaluation Committee. RESULTS: During pregnancy 20.8% of the women were prescribed at least one antibiotic. The 'beta-lactam antibacterials/penicillins' group and the specific antibiotic amoxicillin were most commonly prescribed in the nine trimesters covered. The prescription rate of the 'other antibacterials' group during pregnancy increased over the years, in contrast to that of the 'sulphonamides/trimethoprim' group, which decreased. In total, 2.0% of pregnancies were exposed to a 'potentially harmful' antibiotic and 0.8% to a 'harmful' antibiotic. Compared with the period before conception, 'safe' antibiotics were prescribed more often during pregnancy than the other groups. CONCLUSIONS: One in five women was prescribed at least one antibiotic during pregnancy in the Netherlands, which is comparable with rates in other European countries. Our results suggest that antibiotics appear to be prescribed to pregnant women generally in accordance with national recommendations.

Identifying associations between maternal medication use and birth defects using a case-population approach: an exploratory study on signal detection.

BACKGROUND: The effects of many drugs on the unborn child are unknown. In a case-population design, drug exposure of cases is compared with that of a source population; this kind of study can be useful for generating signals. OBJECTIVE: To see whether a comparison of drug use rates from the birth defect registry EUROCAT NNL (cases) with prescription rates from a population-based prescription database, the IADB (population), could be used to detect signals of teratogenic risk of drugs. METHODS: We defined 3,212 cases from the EUROCAT NNL database, a population-based birth defect registry in the Northern Netherlands and 29,223 population controls from the IADB, a prescription database with data from community pharmacies in the same geographical area, born between 1998 and 2008. We classified the malformations of the 3,212 cases into several malformation groups according to organ system (based on the International Classification of Diseases codes and the EUROCAT guidelines). If a child had multiple malformations in several organ systems (n = 253, 7.9 %), he/she was counted in all the categories represented. For several groups of malformations we calculated rate ratios (RR) and 95 % confidence intervals for drugs acting on the central nervous system and for drugs considered to be safe for use in pregnancy. The RRs were based on first-trimester drug use rates from the cases in the EUROCAT NNL database and prescription rates from the population controls in the IADB. RESULTS: For drugs acting on the central nervous system we found significantly increased RRs for the anti-epileptic drug valproic acid and for some selective serotonin reuptake inhibitors. For drugs considered to be safe only the anti-hypertensive methyldopa showed significantly increased RRs. CONCLUSION: We show that a case-population study is a suitable method for detecting signals of possible teratogenicity, provided that the teratogenic effects and the drugs under study are as specific as possible and the drugs are widely used.

Angiotensin-converting enzyme inhibitor treatment and the development of urinary tract infections: a prescription sequence symmetry analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) can reduce urine output, especially when treatment is first started. Since bacterial clearance from the urinary tract is dependent on urine output, it was hypothesized that ACEi may also increase the risk of urinary tract infections (UTIs). OBJECTIVE: Our objective was to assess the risk of UTIs associated with ACEi therapy initiation in the general population. METHODS: A prescription sequence symmetry analysis was performed with the Dutch 'InterAction Database' (IADB.nl) pharmacy prescription database. We selected all patients from the IADB who were incident users of both ACEi and nitrofurantoin (a proxy for UTIs). A relatively short maximum time-span of 4 weeks between both prescriptions was used to limit time-variant confounding. The sequence ratio was calculated by dividing the number of individuals starting ACEi first and nitrofurantoin second by the number of individuals starting nitrofurantoin treatment first and ACEi second. We adjusted for trends in prescribing and estimated 95 % confidence intervals using exact confidence intervals for binomial distributions. To evaluate whether the effect is specific to ACEi and to assess whether the possible mechanism behind an increased risk of UTIs is related to the renin-angiotensin-aldosterone system, we also estimated the risk for ß-adrenoceptor antagonists (ß-blockers). RESULTS: In total, 22,959 incident users of ACEi therapy were eligible for analysis. Of these, 161 patients started ACEi therapy within 4 weeks prior to or after nitrofurantoin therapy initiation. A total of 101 (63 %) started ACEi therapy first followed by nitrofurantoin treatment, while 60 (37 %) patients started nitrofurantoin treatment first, which corresponds to a statistically significant adjusted sequence ratio (ASR) of 1.68 (95 % CI 1.21-2.36). No association was found between ß-blockers and UTI treatment (ASR 1.01, 95 % CI 0.74-1.38). CONCLUSIONS: A significant excess of patients received UTI medication prescriptions following the first month after ACEi initiation. This prescription sequence asymmetry suggests that ACEi initiation increases the risk of developing UTIs.

A population analysis of prescriptions for asthma medications during pregnancy.

BACKGROUND: It is important to control asthma during pregnancy. However, some studies indicate that women stop or change their asthma medications when they become pregnant. OBJECTIVE: We used a population database to analyze changes in prescriptions for asthma medications to patients before, during, and after pregnancy. METHODS: We collected information from a pregnancy database that is part of the population-based pharmacy prescription InterAction Database from the northern Netherlands. Our study cohort comprised 25,709 pregnancies for which prescription data were available. We collected data over a study period of 1 year before pregnancy until 6 months after birth and analyzed data from pregnant women who received at least 1 prescription for asthma medication during the study period (n = 2072), identifying all prescriptions for asthma medication and oral corticosteroids. RESULTS: Prescriptions for asthma medications did not change during pregnancies from 1994-2003. However, during the 2004-2009 period, there was a significant decrease (P = .017) in prescriptions for asthma medications during the first months of pregnancy compared with the months before pregnancy, especially prescriptions of long-acting bronchodilators. Although most asthma prescriptions continued throughout pregnancy, prescriptions for controller therapies were reduced by 30% during the first months of pregnancy. CONCLUSIONS: Many women stop or reduce their use of asthma medications when they become pregnant. Strategies to safely control asthma during pregnancy are needed.

Psychotropic medication during endocrine treatment for breast cancer.

PURPOSE: Psychological problems are frequently mentioned in women treated for breast cancer in whom depression is mentioned as the most common disorder. The aim was to study the prescription of psychotropic medication in women with endocrine treatment for breast cancer in women in our prospective and consecutive pharmacy database. METHODS: Women (n = 2,172) with at least one prescription of tamoxifen, fulvestrant, anastrazole, letrozole or exemestane were considered as breast cancer patients treated with endocrine therapy. This group was compared with an age- and family physician-matched group of women without cancer (n = 8,129), and the incidence risk ratio (IRR) and the 95% confidence intervals (95% CI) were calculated. In addition, the prevalence of these psychotropic medication prescriptions and the 95% CI were calculated. RESULTS: There was an increased prescription of psychotropic medication in the female breast cancer patients on endocrine therapy: anxiolytics (IRR 2.07, 95% CI 1.87-2.29), hypnotics and sedatives (IRR 2.59, 95% CI 2.34-2.87) and anti-depressants (IRR 1.46, 95% CI 1.28-1.65). The prevalences of anxiolytics, hypnotics and sedatives were also increased in this group, indicating an increased use over time of these drugs. The prevalence of anti-depressant prescription was not increased, indicating short-term use only. CONCLUSIONS: This study indicated increased psychological distress due to breast cancer diagnosis and/or treatment in women on endocrine therapy. Anti-depressants were only prescribed for a short time. These data can contribute to an improved awareness of the impact of breast cancer (treatment) and therefore potentially to the optimizing of support for these patients.