Comparison of antipsychotic drug use in children and adolescents in the Netherlands before and during the COVID-19 pandemic.

This study aims to describe the patterns and trends in antipsychotic prescription among Dutch youth before and during the corona virus disease 2019 (COVID-19) pandemic (between 2017 and 2022). The study specifically aims to determine whether there has been an increase or decrease in antipsychotic prescription among this population, and whether there are any differences in prescription patterns among different age and sex groups. The study utilized the IADB database, which is a pharmacy prescription database containing dispensing data from approximately 120 community pharmacies in the Netherlands, to analyze the monthly prevalence and incidence rates of antipsychotic prescription among Dutch youth before and during the pandemic. The study also examined the prescribing patterns of the five most commonly used antipsychotics and conducted an autoregressive integrated moving average (ARIMA) analysis using data prior to the pandemic, to predict the expected prevalence rate during the pandemic. The prescription rate of antipsychotics for Dutch youth was slightly affected by the pandemic, with a monthly prevalence of 4.56 [4.50-4.62] per 1000 youths before COVID-19 pandemic and 4.64 [4.59-4.69] during the pandemic. A significant increase in prevalence was observed among adolescent girls aged 13-19 years. The monthly incidence rate remained stable overall, but rose for adolescent girls aged 13-19 years. Aripiprazole, and Quetiapine had higher monthly prevalence rates during the pandemic, while Risperidone and Pipamperon had lower rates. Similarly, the monthly incidence rates of Aripiprazole and Olanzapine went up, while Risperidone went down. Furthermore, the results from the ARIMA analysis revealed that despite the pandemic, the monthly prevalence rate of antipsychotic prescription was within expectation. The findings of this study suggest that there has been a moderate increase in antipsychotic prescription among Dutch youth during the COVID-19 pandemic, particularly in adolescent females aged 13-19 years. However, the study also suggests that factors beyond the pandemic may be contributing to the rise in antipsychotic prescription in Dutch youth.

The relationship between childhood leukaemia and childhood asthma: A pharmacoepidemiological study from the Netherlands.

BACKGROUND: It has been suggested that childhood asthma lowers the risk of childhood leukaemia. Studies have found an inverse association between these conditions. However, most studies on this relationship are based on questionnaires and telephone interviews, introducing recall bias. Therefore, we conducted a matched case-control study based on drug prescription data to assess the relationship between both conditions. METHODS: In a large database, covering more than one million individuals, we identified cases of children who had been prescribed 6-mercaptopurine (6-MP). This drug is used in the outpatient maintenance therapy of childhood leukaemia. We matched every child with leukaemia on sex and age (±6 months) to children without leukaemia (controls). The variable of having had asthma was defined as receiving at least two prescriptions for an inhaled corticosteroid within 12 months. RESULTS: We identified 59 children aged 2-18 who had been prescribed 6-MP (cases), and they were matched to 21,918 controls. Of the children with childhood leukaemia, three (5%) had childhood asthma, whereas in the control group 4889 (22%) had childhood asthma (odds ratio [OR] 0.19; 95% confidence interval 0.06-0.60). CONCLUSION: In this study on the relationship between childhood asthma and childhood leukaemia, we found a strong inverse association.

Exposure to psychotropic drugs before and during pregnancy: what has changed over the last two decades?

Trends in prescribing psychotropic drugs before and during pregnancy may have changed over the years, but actual information is lacking. We therefore compared and assessed the exposure and acceptance rates of classes of antipsychotic (+ lithium), anxiolytic, sedative/hypnotic, antidepressant, and psychostimulant before and during pregnancy in the past two decades. All singleton pregnancies with ≥1 prescription of psychotropic drug from six months before pregnancy until child's birthdate were identified in the pregnancy subset of the IADB.nl prescription database. The prescription patterns of psychotropics were distinguished as continuation rate (CR), initiation rate (IR), discontinuation rate (DR), total exposure rate (TER), and acceptance rate. Singleton pregnancies exposed to psychotropic drugs before and during pregnancy increased from 118.4 to 136.5 (per 1000 singleton pregnancies) between decades. Changing trends were observed in decade 2, including a high increase in the TER of antipsychotic class (3.3 to 6.8) and antidepressant class (23.0 to 40.6). A marked increase for individual drugs was seen for sertraline (TER: 0.6 to 6.6 and PAT: 35.3% to 82.5%), citalopram (TER: 2.3 to 10.0 and PAT: 51.1% to 74.6%), and quetiapine (TER: 0.4 to 3.1 and PAT: 57.1% to 66.0%). Although the total exposure rates of five classes of psychotropics in singleton pregnancies increased in decade 2, only antidepressant class had a higher acceptance rate during pregnancy. Certain SSRI antidepressants and atypical antipsychotics were more frequently prescribed in decade 2 than in decade 1, reflecting that treatment options were preferred for safer treatment choices.

Switching pattern and dose adjustment of antidepressants before and during pregnancy.

The purpose of the study is to examine the switching pattern and dose adjustment of antidepressants (ADs) prescribed to women from six months before to six months during pregnancy in the Netherlands. The recorded dispenses or refills were collected from the University of Groningen IADB.nl pregnancy subset for all singleton pregnancies in which the mother received ≥ 1 prescription of an AD dispensed before pregnancy and was present in the database at least six months after conception. The rates of continuation, discontinuation, and switching between 2001 and 2020 were assessed for the ADs studied. The mean number of Defined Daily Doses (DDDs) of the most frequently continued ADs used was calculated both before and during pregnancy, and a paired t-test was used to test for significant changes. The continuation rates for AD users, especially for SSRI and SNRI continued users, increased over time from 27% and 19% (2001-2005) to 65% and 65% (2016-2020). The switching rate between ADs remained consistently low from the start of the study (2001-2005) at 2.0% to the end of the study (2016-2020) at 2.3%. Most women who switched between antidepressants during pregnancy received a different SSRI monotherapy (85%), followed by an SNRI (6%), a TCA (4%), and an "other AD" (4%). In most cases observed, the dose adjustment for the mean DDDs during pregnancy compared to the mean DDDs before pregnancy only changed little (less than 10%). Continued use of SSRIs among singleton pregnancies doubled over the study period. The low rate of AD switching and little changes in the DDD adjustment for most AD continuers indicate that pregnant women prefer to continue their prepregnancy medication rather than switch it. Most observed findings cohere with the Dutch national guidelines for antidepressant use during pregnancy.

Risk of neuropsychiatric adverse events associated with varenicline treatment for smoking cessation among Dutch population: A sequence symmetry analysis.

PURPOSE: Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real-world setting. METHODS: We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time-intervals. Adjusted sequence ratios (aSR) were calculated for each time-interval. RESULTS: Within 365-days' time-interval 1066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa (crude sequence ratio [cSR] 0.90, 95% CI: 0.80-1.02). After adjustments for trends in prescriptions, overall a null association was found (aSR 1.00, 95% CI: 0.89-1.13). Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time-interval. A small transient increased risk was found for sleep disorders, particularly in earlier time-intervals 3 and 6 months (aSRs 1.52, 95% CI: 1.10-2.11 and 1.45, 95% CI: 1.15-1.83, respectively). Subgroup and sensitivity analyses showed similar findings. CONCLUSIONS: Varenicline initiation was unlikely to be associated with an increased risk of taking anti-depressants nor anti-anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation.

Comparing the EQ-5D-3 L and EQ-5D-5 L: studying measurement and scores in Indonesian type 2 diabetes mellitus patients.

BACKGROUND: The EuroQoL five-dimensional instrument (EQ-5D) is the favoured preference-based instrument to measure health-related quality of life (HRQoL) in several countries. Two versions of the EQ-5D are available: the 3-level version (EQ-5D-3 L) and the 5-level version (EQ-5D-5 L). This study aims to compare specific measurement properties and scoring of the EQ-5D-3 L (3 L) and EQ-5D-5 L (5 L) in Indonesian type 2 diabetes mellitus (T2DM) outpatients. METHODS: A survey was conducted in a hospital and two primary healthcare centres on Sulawesi Island. Participants were asked to complete the two versions of the EQ-5D instruments. The 3 L and 5 L were compared in terms of distribution and ceiling, discriminative power and test-retest reliability. To determine the consistency of the participants' answers, we checked the redistribution pattern, i.e., the consistency of a participant's scores in both versions. RESULTS: A total of 198 T2DM outpatients (mean age 59.90 ± 11.06) completed the 3 L and 5 L surveys. A total of 46 health states for 3 L and 90 health states for 5 L were reported. The '11121' health state was reported most often: 17% in the 3 L and 13% in the 5 L. The results suggested a lower ceiling effect for 5 L (11%) than for 3 L (15%). Regarding redistribution, only 6.1% of responses were found to be inconsistent in this study. The 5 L had higher discriminative power than the 3 L version. Reliability as reflected by the index score was 0.64 for 3 L and 0.74 for 5 L. Pain/discomfort was the dimension mostly affected, whereas the self-care dimension was the least affected. CONCLUSIONS: This study suggests that the 5 L-version of the EQ-5D instrument performs better than the 3 L-version in T2DM outpatients in Indonesia, regarding measurement and scoring properties. As such, our study supports the use of the 5 L as the preferred health-related quality of life measurement tool. We did not do a trial but this study was approved by the Medical Ethics Committee of Universitas Gadjah Mada Yogyakarta, Indonesia (document number KE/FK/1188/EC, 12 November 2014, amended 16 March 2015).

'Diabetes is a gift from god' a qualitative study coping with diabetes distress by Indonesian outpatients.

BACKGROUND: More than two-thirds of patients diagnosed with type 2 diabetes mellitus (T2DM) in Indonesia encounter medical-related problems connected to routine self-management of medication and the social stigma related to T2DM. The current study aims to explore distress and coping strategies in Indonesian T2DM outpatients in a Primary Healthcare Centre (PHC) in Surabaya, East Java, Indonesia. METHODS: We conducted a qualitative study using two different data collection methods: focus group discussions and in-depth interviews. The guideline of interviews and discussions were developed based on seventeen questions derived from the DDS17 Bahasa Indonesia (a Bahasa Indonesia version of the Diabetes Distress Scale questionnaire), which covered physician distress domain, emotional burden domain, regimen distress domain and interpersonal distress domain. RESULTS: The majority of the 43 participants were females and aged 50 or older. Our study discovered two main themes: internal and external diabetes distress and coping strategies. Internal diabetes distress consists of disease burden, fatigue due to T2DM, fatigue not due to T2DM, emotional burden (fear, anxiety, etc.) and lack of knowledge. Internal coping strategies comprised spirituality, positive attitude, acceptance and getting more information about T2DM. External diabetes distress was evoked by distress concerning healthcare services, diet, routine medication, monthly blood sugar checks, interpersonal distress (family) and financial concern. External coping strategies included healthcare support, traditional medicine, vigilance, self-management, social and family support and obtaining information about health insurance. CONCLUSION: Our study shows that for Indonesian T2DM-patients, spirituality and acceptance are the most common coping mechanisms for reducing DD. Furthermore, our study revealed an overall positive attitude towards dealing with T2DM as well as a need for more information about T2DM and potential coping strategies. Finally, an important finding of ours relates to differences in DD between males and females, potential DD associated with health services provision and the specific challenges faced by housewives with T2DM.

A Prescription Trend Analysis of Methylphenidate: Relation to Study Reports on Efficacy.

Use of methylphenidate in children has increased substantially, despite conflicting evidence regarding efficacy. In this study, prescription data were analyzed in relation to the publication of new evidence regarding efficacy. Incidence rates and prescribed doses of methylphenidate increased, with a decline during the last few years. Duration of use is still increasing. In half of the cases, starting dosages are higher than recommended in guidelines. There was little evidence that publication of new evidence directly influenced the use of methylphenidate. Recent and critical study findings should receive more attention to contribute to the development and use of treatment guidelines for ADHD and evidence-based methylphenidate use.

Antidepressant use during pregnancy and the risk of developing gestational hypertension: a retrospective cohort study.

BACKGROUND: Prior studies reported that exposure to antidepressants during pregnancy may be associated with gestational hypertension. The aim of this study is to assess the association between the use of antidepressants during pregnancy and the risk of developing gestational hypertension. METHODS: A retrospective cohort study using the prescription database IADB.nl was conducted among nulliparous women with singleton pregnancies between 1994 and 2015 in the Netherlands. Logistic regression analysis was used to estimate odds ratios (OR), adjusted OR (aOR) and their corresponding 95% confidence intervals (95% CI). Gestational hypertension as main outcome measure was defined as at least one dispensed record of an antihypertensive drug (methyldopa, nifedipine, labetalol, ketanserin, nicardipine) after 20 weeks of gestation until 14 days after delivery. Sub-analyses were conducted for class of antidepressant, duration and amount of use of antidepressant (≤30, ≥30 Defined Daily Doses or DDDs), and maternal age. Sensitivity analyses to assess uncertainties were conducted. RESULTS: Twenty-eight thousand twenty women were included, of which 539 (1.92%) used antidepressants. The risk of gestational hypertension was doubled for women using antidepressant (aOR 2.00 95% CI 1.28-3.13). Significant associations were also found for the subgroup selective serotonin reuptake inhibitors (SSRIs) (aOR 2.07 95% CI 1.25-3.44), ≥30 DDDs (aOR 2.50 95% CI 1.55-3.99) and maternal age of 30-34 years (aOR 2.59 95% CI 1.35-4.98). Varying the theoretical gestational age showed comparable results. CONCLUSION: Prolonged use of antidepressants during the first 20 weeks of gestation appeared to be associated with an increased risk of developing gestational hypertension. When balancing the benefits and risks of using these drugs during pregnancy, this should be taken into account.

Association between medication prescription for atopic diseases and attention-deficit/hyperactivity disorder.

BACKGROUND: Data on the association between atopic diseases and attention-deficit/hyperactivity disorder (ADHD) have been inconclusive. OBJECTIVE: To assess whether children with drug-treated ADHD are more likely to receive treatment for asthma, allergic rhinitis, or eczema before the start of ADHD medication use compared with controls and to examine the effect of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. METHODS: We conducted a retrospective nested case-control study among children (6-12 years of age) using the Groningen University prescription database. Cases were defined as children with at least 2 prescriptions of methylphenidate within 12 months. For each case, 4 controls were matched on age, sex, and regional area code. Parental prescription data were linked to cases and controls to assess the influence of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. RESULTS: We identified 4257 cases and 17,028 matched controls. Drug treatment for asthma, allergic rhinitis, and eczema was more common in cases than controls (adjusted odds ratios [aORs], 1.4 [95% confidence interval (CI), 1.3-1.6], 1.4 [95% CI, 1.1-1.8], and 1.3 [95% CI, 1.1-1.5], respectively). Medication for allergic rhinitis and asthma among parents was associated with ADHD treatment in their children (aORs, 1.3 [95% CI, 1.1-1.5] and 1.2 [95% CI, 1.1-1.3], respectively). CONCLUSION: This study provides further evidence to support the hypothesis that atopic diseases are associated with ADHD. The parental-offspring association suggests a possible genetic and/or environmental component.

Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands: choice of antidepressant and dose.

The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended. We aimed to determine whether antidepressant prescriptions are in accord with guidelines. A cohort of young people aged between 6 and 17 at the time of antidepressant initiation was selected from IABD, a Dutch pharmacy prescription database. The percentage of prescriptions for each antidepressant was determined. Starting and maintenance doses were determined and compared with recommendations for citalopram, fluoxetine, fluvoxamine, and sertraline. During the study period, 2942 patients initiated antidepressant treatment. The proportion of these young people who were prescribed fluoxetine increased from 10.1 % in 1994-2003 to 19.7 % in 2010-2014. However, the most commonly prescribed antidepressants were paroxetine in 1994-2003 and citalopram in 2004-2014. The median starting and maintenance doses were ≤0.5 DDD/day for tricyclic antidepressants and 0.5-1 DDD/day for SSRIs and other antidepressants. Starting doses were guideline-concordant 58 % of the time for children, 31 % for preteens, and 16 % for teens. Sixty percent of teens were prescribed an adult starting dose. In conclusion, guideline adherence was poor. Physicians preferred citalopram over fluoxetine, in contrast to the recommendations. Furthermore, although children were prescribed a low starting dose relatively frequently, teens were often prescribed an adult starting dose. These results suggest that dedicated effort may be necessary to improve guideline adherence.

Comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events-a real-world longitudinal inception cohort study.

Introduction: Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events. Methods: Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64-0.97 and 0.69-0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19-0.98) for ARBs and 0.32 (CI: 0.13-0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1. Conclusion: The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDT with BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs.

The Therapeutic Potential of Essential Oils in Managing Inflammatory Skin Conditions: A Scoping Review.

Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree (Melaleuca alternifolia) oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain (Trachyspermum ammi) oil, eucalyptus (Eucalyptus globulus) oil, and cedarwood (Cedrus libani) oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kanuka (Kunzea ericoides) oil and frankincense (Boswellia spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.

Long-term comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events: a population-based retrospective inception cohort study in the Netherlands.

OBJECTIVE: To determine the long-term effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events. DESIGN: Retrospective inception cohort study covering a 25-year study period. SETTING: University Groningen IADB.nl pharmacy prescription database with data from 1996 to 2020. PARTICIPANTS: Patients aged 18 years or older, free of any cardiovascular disease (CVD) drug therapies prior to initiation of a preventive antihypertensive monotherapy (ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs) and thiazides). OUTCOME MEASURES: Primary outcome was the time to first prescription of acute cardiac drug therapy (CDT) measured by valid drug proxies to identify a first major CVD event in patients without a history of CVD. RESULTS: Among 33 427 initiators, 5205 (15.6%) patients experienced an acute CDT. The average follow-up time was 7.9±5.5 years. The 25-year incidence rate per 1000 person-years were 25.3, 22.4, 18.2, 24.4 and 22.0 for ACEI, ARB, BB, CCB and thiazide starters, respectively. Inverse probability of treatment-weighted Cox regression showed that thiazide starters had lower hazards than the reference BB starters (HR: 0.88, 95% CI: 0.81 to 0.95). Among patients on diabetes drugs, risks were lower (HR: 0.49, 95% CI: 0.28 to 0.85). CCB starters had higher hazards than reference BB (HR: 1.21, 95% CI: 1.07 to 1.36). The overall estimated number needed to treat for thiazides compared with BBs to prevent one acute CDT in 25 years was 26, and four among patients on diabetes drugs. CONCLUSIONS: After adjustments for confounders, patients starting on monotherapy with thiazides had a lower incidence of CDT compared with those starting on BBs, notably among patients on diabetes drugs. Conversely, patients who began CCB monotherapy had a higher incidence of CDT compared with those starting on BBs. Other monotherapies had comparable incidence of cardiovascular disease compared with BBs.

Real-World Dispensing Patterns of Inhalation Medication in Young Adult Asthma: An Inception Cohort Study.

Purpose: The Global Initiative for Asthma (GINA) suggests a step-wise approach for pharmacological treatment of asthma. Valid study of real-world treatment patterns using dispensing databases includes proper measurement of medication adherence. We aim to explore such patterns by applying a time-varying proportion of days covered (tPDC)-based algorithm. Patients and Methods: We designed a retrospective inception cohort study using the University of Groningen IADB.nl community pharmacy dispensing database. Included were 19,184 young adults who initiated asthma medication anywhere between 1994 and 2021, in the Netherlands. Main treatment steps were defined as: 1 - SABA/ICS-formoterol as needed, 2 - low dose ICS, 3 - low dose ICS + LABA or tiotropium, or intermediate dose ICS, 4 - intermediate to high dose ICS + LABA or tiotropium, triple therapy, or high dose ICS, 5 - treatment prescribed by a specialist. Changes in treatment steps were determined using a time-varying proportion of days covered (tPDC)-based algorithm. Individual drug treatment trajectories were visualized over time using a lasagna plot. Results: At initiation, of the 19,184 included individuals, 52%, 7%, 15%, 16%, and 10% started treatment in steps 1 to 5, respectively. The median (IQR) follow-up time was 3 (1-7) years. Median (IQR) number of switches was 1 (0-3). Comparing starting step to last observed step, 37% never switched between treatment steps, 20% of individuals stepped down and 22% stepped up. Conclusion: The low proportion of treatment switches between steps indicates that tailoring of treatment to patients' needs might be suboptimal. The tPDC-based algorithm functions well in translating dispensing data into continuous drug-utilization data, enabling a more granular assessment of treatment patterns among asthma patients.

Association between Incidence of Prescriptions for Alzheimer's Disease and Beta-Adrenoceptor Antagonists: A Prescription Sequence Symmetry Analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, with a growing number of patients worldwide. The association between AD and treatment with drugs targeting the beta-adrenergic receptor is controversial. The aim of this study is to assess the association between the initiation of AD medication and beta-adrenoceptor antagonists (beta-blockers) in adults. MATERIALS AND METHODS: We conducted a prescription sequence symmetry analysis using the University of Groningen IADB.nl prescription database. We determined the order of the first prescription for treating AD and the first prescription for beta-blockers, with the dispensing date of the first prescription for AD defined as the index date. Participants were adults over 45 years old starting any AD medication and beta-blockers within two years. We calculated adjusted sequence ratios with corresponding 95% confidence intervals. RESULTS: We identified 510 users of both AD and beta-blockers, and 145 participants were eligible. The results were compatible with either a significant decrease in the incidence of AD after using beta-blockers (adjusted sequence ratio (aSR) = 0.52; 95% CI: 0.35-0.72) or, conversely, an increase in beta-blockers after AD medication (aSR = 1.96; 95% CI: 1.61-2.30). CONCLUSIONS: There is a relationship between the use of beta-blockers and AD medications. Further research is needed with larger populations to determine whether drug therapy for AD increases the risk of hypertension or whether beta-blockers have potential protective properties against AD development.

Community Use of Repurposed Drugs Before and During COVID-19 Pandemic in the Netherlands: An Interrupted Time-Series Analysis.

Background: Repurposing registered drugs could reduce coronavirus disease (COVID-19) burden before novel drugs are authorized. Little is known about how the pandemic and imposed restrictions changed their dispensing. We aimed to investigate the impact of COVID-19 pandemic on repurposed drugs dispensing in the Netherlands. Methods: We performed interrupted time-series study using University of Groningen prescription database IADB.nl to evaluate dispensing trends of 24 repurposed drugs before (2017-February 2020) and after (March 2020-2021) the pandemic' start. Primary outcomes were monthly prevalence and incidence rates. An autoregressive integrated moving average model assessed the effect of pandemic and stringency index (measuring strictness of government's restriction policies). Results: Annual number of IADB.nl population ranged from 919,697 to 952,400. Generally, dispensing of common long-term-used drugs was not significantly affected by pandemic. The prevalence of antibacterials (-4.20 users per 1000 people), antivirals (-0.04), corticosteroids (-1.29), prednisolone (-1.32), calcium channel blocker (-0.41), and diuretics (-1.29) was lower than expected after the pandemic's start, while the prevalence of ivermectin (0.07), sulfonylureas (0.15), sodium-glucose co-transporter-2 (SGLT2) inhibitor (0.17), and anticoagulants (1.95) was higher than expected. The pandemic was associated with statistically significant decreases in the incidence of antibacterials (-1.21), corticosteroids (-0.60), prednisolone (-0.64) and anticoagulants (-0.02), and increases in ivermectin (0.02), aggregated antidiabetic drugs (0.13), and SGLT2 inhibitors (0.06). These trends were positively associated with pandemic and negatively associated with stringency index. Conclusion: Dispensing of most drugs was not significantly associated with pandemic and government's response. Despite some statistically significant disruptions, these were not necessarily clinically relevant due to small absolute differences observed.

Trigeminovascular effects of propranolol in men and women, role for sex steroids.

OBJECTIVE: Assess whether propranolol modulates the trigeminovascular system in both men and women. METHODS: We investigated the effect of propranolol (80 mg, 90 min after oral administration, corresponding to Tmax ) on the increase in dermal blood flow of the forehead skin (innervated by the trigeminal nerve) by capsaicin application (0.6 mg/mL) and electrical stimulation (0.2-1.0 mA) before and after placebo (grapefruit juice) or propranolol (oral solution diluted in grapefruit juice) in a randomized, double-blind, placebo-controlled cross-over study, including healthy males (n = 10) and females on contraceptives (n = 11). Additionally, we compared our results with data from the Dutch IADB.nl prescription database by analyzing the change in triptan use after propranolol prescription in a population similar to our dermal blood flow study subjects (males and females, 20-39 years old). RESULTS: Dermal blood flow responses to capsaicin were significantly attenuated after propranolol, but not after placebo. When stratifying by sex, no significant changes in the capsaicin-induced dermal blood flow were observed in females after propranolol, whereas they remained significant in males. Dermal blood flow responses to electrical stimulation were not modified in any case. In our prescription database study, after propranolol, a more pronounced decrease in triptan use was observed in male patients than in female patients. INTERPRETATION: Propranolol (80 mg) inhibits capsaicin-induced increases in dermal blood flow in a sex-dependent manner. In patients, a more pronounced decrease in triptan use is observed in males when compared with females, suggesting an interaction between propranolol and sex steroids in the modulation of the trigeminovascular system.

Neuropsychiatric safety of varenicline in the general and COPD population with and without psychiatric disorders: a retrospective cohort study in a real-world setting.

OBJECTIVES: To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD) population with and without psychiatric disorders compared with nicotine replacement therapy (NRT) to strengthen the knowledge of varenicline safety. DESIGN: A retrospective cohort study. SETTING: Prescription database IADB.nl, the Netherlands. PARTICIPANTS: New users of varenicline or NRT among general (≥18 years) and COPD (≥40 years) population. Psychiatric subcohort was defined as people prescribed psychotropic medications (≥2) within 6 months before the index date. OUTCOME MEASURES: The incidence of NPAEs including depression, anxiety and insomnia, defined by new or naive prescriptions of related medications in IADB.nl within 24 weeks after the first treatment initiation of varenicline or NRT. RESULTS: For the general population in non-psychiatric cohort, the incidence of total NPAEs in varenicline (4480) and NRT (1970) groups was 10.5% and 12.6%, respectively (adjusted OR (aOR) 0.85, 95% CI 0.72 to 1.00). For the general population in psychiatric cohort, the incidence of total NPAEs was much higher, 75.3% and 78.5% for varenicline (1427) and NRT (1200) groups, respectively (aOR 0.82, 95% CI 0.68 to 0.99). For the COPD population (1598), there were no differences in the incidence of NPAEs between comparison groups in both the psychiatric cohort (aOR 0.97, 95% CI 0.66 to 1.44) and non-psychiatric cohort (aOR 0.81, 95% CI 0.54 to 1.20). Results from subgroup or sensitivity analyses also did not reveal increased risks of NPAEs but showed decreased risk of some subgroup NPAEs associated with varenicline. CONCLUSIONS: In contrast to the concerns of a possible increased risk of NPAEs among varenicline users, we found a relative decreased risk of total NPAEs in varenicline users of the general population in psychiatric or non-psychiatric cohorts compared with NRT and no difference for NPAEs between varenicline and NRT users in smaller population with COPD.