Vasopressin and parental expressed emotion in the transition to fatherhood.

In the last decades, parenting researchers increasingly focused on the role of fathers in child development. However, it is still largely unknown which factors contribute to fathers' beliefs about their child, which may be crucial in the transition to fatherhood. In the current randomized within-subject experiment, the effect of nasal administration of vasopressin (AVP) on both Five Minute Speech Sample-based (FMSS) expressed emotion and emotional content or prosody was explored in 25 prospectivefathers. Moreover, we explored how the transition to fatherhood affected these FMSS-based parameters, using prenatal and early postnatal measurements. Analyses revealed that FMSS-based expressed emotion and emotional content were correlated, but not affected by prenatal AVP administration. However,child's birth was associated with an increase in positivity and a decrease in emotional prosody, suggesting that the child's birth is more influential with regard to paternal thoughts and feelings than prenatal AVP administration.

Effects of vasopressin on neural processing of infant crying in expectant fathers.

In a randomized, double blind, placebo-controlled, within-subject magnetic resonance imaging study, we examined the effect of 20 IU intranasal vasopressin on the neural processing of infant crying in 25 fathers-to-be. We explored whether familial background modulates vasopressin effects, and whether vasopressin differentially affects cry processing coupled with neutral or emotional contextual information. Participants listened to cries accompanied by neutral ('this is an infant') or emotional ('this infant is sick/bored') contextual information, and neutral control sounds ('this is a saw'). Additionally, participants reported on their childhood experiences of parental love-withdrawal and abuse. Infant crying (vs control sounds) was associated with increased activation in the bilateral auditory cortex and posterior medial cortex. No effects of vasopressin were found in this 'cry network'. Exploratory whole-brain analyses suggested that effects of vasopressin in the anterior cingulate cortex, paracingulate gyrus and supplemental motor area were stronger in fathers who experienced lower (vs higher) levels of love-withdrawal. No interaction was observed for abuse. Vasopressin increased activation in response to cries accompanied by emotional vs neutral contextual information in several brain regions, e.g. the cerebellum, brainstem (midbrain), posterior medial cortex, hippocampus, putamen, and insula. Our results suggest that the experience of love-withdrawal may modulate the vasopressin system, influencing effects of vasopressin administration on cry processing. Results further suggest a role for vasopressin in the processing of cry sounds with emotional contextual information.

Periconceptional parental conditions and perimembranous ventricular septal defects in the offspring.

BACKGROUND: The perimembranous ventricular septal (pVSD) defect is the most common congenital heart disease phenotype. Several parental factors are associated with pVSD risk in the offspring. To contribute to the future prevention of pVSDs, we investigated associations with nongenetic parental conditions. METHODS: In a case-control study with standardized data collection at 17 months after birth, 115 parents of a child with pVSD and 484 parents of a healthy child completed questionnaires about periconceptional nongenetic conditions. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Complete data were available for 588 families (98%). Maternal risk conditions associated with pVSD offspring were a positive family history of congenital heart disease (OR, 2.61; 95%CI, 0.98-6.91), medication use (OR, 1.80; 95%CI, 1.13-2.85) and advanced age (OR, 1.07; 95%CI, 1.02-1.12). Exposure to phthalates (OR, 1.93; 95%CI, 1.05-3.54) was the only paternal risk condition associated with pVSD offspring. CONCLUSION: Four periconceptional parental conditions contributed to pVSD risk in the offspring. Couples planning pregnancy should be counseled on these risk conditions which are partially modifiable to contribute to the future prevention of pVSDs.

Association between ADHD drug use and injuries among children and adolescents.

To study the association between attention deficit hyperactivity disorder (ADHD) drug use and the incidence of hospitalization due to injuries. A random sample of 150,000 persons (0-18 years) was obtained from the Dutch PHARMO record linkage system. An ADHD medication cohort as well as an up to six age/sex/index date sampled control cohort with no history of ADHD drug use was formed. Differences in incidence of hospitalization due to injuries were stratified for age and sex and compared prior, during and after exposure on ADHD drugs. The overall incidence of hospital admissions for injuries was two times higher in the ADHD medication cohort [incidence rate ratios (IRR) 2.2 (95 % CI 1.6-2.9)]. The incidence rate for injuries during exposure to ADHD drugs was lower in the exposed period compared to the period prior to ADHD drug use, although the difference was not statistically significant [IRR 0.68 (95 % CI 0.29-1.60)]. The relative risk for injuries was almost five times higher in the ADHD medication cohort among those who concomitantly used other psychotropics [IRR 4.8 (95 % CI 1.4-16.9)]. Risk for injuries was highest in 12-18 years olds. Children and adolescents using ADHD medication showed a twofold risk for hospital admissions for injuries. ADHD drug use might diminish the increased injury risk, but still overall risk is higher than in age/sex sampled children and adolescents without treatment with ADHD drugs. Use of ADHD and concomitant psychotropics increases the risk for injuries compared to only ADHD drug use.

Deriving Treatment Decision Support From Dutch Electronic Health Records by Exploring the Applicability of a Precision Cohort-Based Procedure for Patients With Type 2 Diabetes Mellitus: Precision Cohort Study.

BACKGROUND: The rapidly increasing availability of medical data in electronic health records (EHRs) may contribute to the concept of learning health systems, allowing for better personalized care. Type 2 diabetes mellitus was chosen as the use case in this study. OBJECTIVE: This study aims to explore the applicability of a recently developed patient similarity-based analytics approach based on EHRs as a candidate data analytical decision support tool. METHODS: A previously published precision cohort analytics workflow was adapted for the Dutch primary care setting using EHR data from the Nivel Primary Care Database. The workflow consisted of extracting patient data from the Nivel Primary Care Database to retrospectively generate decision points for treatment change, training a similarity model, generating a precision cohort of the most similar patients, and analyzing treatment options. This analysis showed the treatment options that led to a better outcome for the precision cohort in terms of clinical readouts for glycemic control. RESULTS: Data from 11,490 registered patients diagnosed with type 2 diabetes mellitus were extracted from the database. Treatment-specific filter cohorts of patient groups were generated, and the effect of past treatment choices in these cohorts was assessed separately for glycated hemoglobin and fasting glucose as clinical outcome variables. Precision cohorts were generated for several individual patients from the filter cohorts. Treatment options and outcome analyses were technically well feasible but in general had a lack of statistical power to demonstrate statistical significance for treatment options with better outcomes. CONCLUSIONS: The precision cohort analytics workflow was successfully adapted for the Dutch primary care setting, proving its potential for use as a learning health system component. Although the approach proved technically well feasible, data size limitations need to be overcome before application for clinical decision support becomes realistically possible.

One-year evaluation of people recovering from COVID-19 receiving allied primary healthcare: A nationwide prospective cohort study.

BACKGROUND: A Dutch nationwide prospective cohort study was initiated to investigate recovery trajectories of people recovering from coronavirus disease 2019 (COVID-19) and costs of treatment by primary care allied health professionals. OBJECTIVES: The study described recovery trajectories over a period of 12 months and associated baseline characteristics of participants recovering from COVID-19 who visited a primary care allied health professional. It also aimed to provide insight into the associated healthcare and societal costs. METHODS: Participants completed participant-reported standardized outcomes on participation, health-related quality of life, fatigue, physical functioning, and costs at baseline (ie, start of the treatment), 3, 6, 9 and 12 months. RESULTS: A total of 1451 participants (64 % women, 76 % mild/moderate severity) with a mean (SD) age of 49 (12) years were included. Linear mixed models showed significant and clinically relevant improvements over time in all outcome measures between baseline and 12 months. Between 6 and 12 months, we found significant but not clinically relevant improvements in most outcome measures. Having a worse baseline score was the only baseline factor that was consistently associated with greater improvement over time on that outcome. Total allied healthcare costs (mean €1921; SEM €48) made up about 3% of total societal costs (mean €64,584; SEM €3149) for the average participant in the cohort. CONCLUSIONS: The health status of participants recovering from COVID-19 who visited an allied health professional improved significantly over a 12-month follow-up period, but nearly the improvement occurred between baseline and 6 months. Most participants still reported severe impairments in their daily lives, and generated substantial societal costs. These issues, combined with the fact that baseline characteristics explained little of the variance in recovery over time, underscore the importance of continued attention for the management of people recovering from COVID-19. TRIAL REGISTRATION: clinicaltrials.gov (NCT04735744).

First year of life medication use and hospital admission rates: premature compared with term infants.

OBJECTIVE: To compare hospitalization and medication use during the first year of life in preterm-born and term-born infants. STUDY DESIGN: Data for this retrospective cohort study were obtained from the linked PHARMO-Netherlands Perinatal Registry cohort. From this linked birth cohort, preterm infants (<37 weeks) born between 2004 and 2007 were randomly matched to 4 full-term infants. During follow-up, hospitalization and medication use were assessed. Cox proportional hazard regression models were used to estimate and compare the relative risk (RR) of hospitalization and medication use in preterm and full-term infants. Population-attributable risk percentages were calculated to estimate the proportion of hospitalizations and medication use attributable to preterm birth. RESULTS: Among the 71,607 singletons born between 2004-2007, 4277 (6%) were born preterm. Of these, 90% were hospitalized at birth, compared with 55% of full-term infants. Preterm infants were twice as likely to be rehospitalized (RR, 2.0; 95% CI, 1.9-2.2), specifically for respiratory-related diseases. Prematurity accounted for 6% of the respiratory disease readmissions. The most frequently used outpatient drugs in the second half year of life were antibacterials for systemic use and drugs for obstructive airway diseases. Preterm infants were 50% more likely to receive a respiratory medication (RR, 1.5; 95% CI, 1.4-1.7). CONCLUSION: In the first year of life, preterm born infants are up to 2 times more likely than full-term infants to be hospitalized or use medication, especially related to respiratory disease.

Healthcare utilization patterns for knee and hip osteoarthritis before and after changes in national health insurance coverage: a data linkage study from the Netherlands.

INTRODUCTION: Medical guidelines aim to stimulate stepped care for knee and hip osteoarthritis, redirecting treatments from hospitals to primary care. In the Netherlands, this development was supported by changing health insurance coverage for physio/exercise therapy. The aim of this study was to evaluate healthcare utilization patterns before and after health changes in health insurance coverage. METHOD: We analyzed electronic health records and claims data from patients with osteoarthritis in the knee (N = 32,091) and hip (N = 16,313). Changes between 2013 and 2019 in the proportion of patients treated by the general practitioner, physio/exercise therapist or orthopedic surgeon within 6 months after onset were assessed. RESULTS: Joint replacement surgeries decreased for knee (OR 0.47 [0.41-0.54]) and hip (OR 0.81 [0.71-0.93]) osteoarthritis between 2013-2019. The use of physio/exercise therapy increased (knee: OR 1.38 [1.24-1.53], hip: OR 1.26 [1.08-1.47]). However, the proportion treated by a physio/exercise therapist decreased for patients that had not depleted their annual deductibles (knee: OR 0.86 [0.79 - 0.94], hip: OR 0.90 [0.79 - 1.02]). This might be affected by the inclusion of physio/exercise therapy in basic health insurance in 2018. CONCLUSION: We have found a shift from hospitals to primary care in knee and hip osteoarthritis care. However, the use of physio/exercise therapy declined after changes in insurance coverage for patients that had not depleted their deductibles.

Evaluation of Primary Allied Health Care in Patients Recovering From COVID-19 at 6-Month Follow-up: Dutch Nationwide Prospective Cohort Study.

BACKGROUND: Patients recovering from COVID-19 often experience persistent problems in their daily activities related to limitations in physical, nutritional, cognitive, and mental functioning. To date, it is unknown what treatment is needed to support patients in their recovery from COVID-19. OBJECTIVE: This study aimed to evaluate the primary allied health care of patients recovering from COVID-19 at 6-month follow-up and to explore which baseline characteristics are associated with changes in the scores of outcomes between baseline and 6-month follow-up. METHODS: This Dutch nationwide prospective cohort study evaluated the recovery of patients receiving primary allied health care (ie, dietitians, exercise therapists, occupational therapists, physical therapists, and speech and language therapists) after COVID-19. All treatments offered by primary allied health professionals in daily practice were part of usual care. Patient-reported outcome measures on participation, health-related quality of life, fatigue, physical functioning, and psychological well-being were assessed at baseline and at 3- and 6-month follow-up. Linear mixed model analyses were used to evaluate recovery over time, and uni- and multivariable linear regression analyses were used to examine the association between baseline characteristics and recovery. RESULTS: A total of 1451 adult patients recovering from COVID-19 and receiving treatment from 1 or more primary allied health professionals were included. For participation (Utrecht Scale for Evaluation of Rehabilitation-Participation range 0-100), estimated mean differences of at least 2.3 points were observed at all time points. For the health-related quality of life (EuroQol Visual Analog Scale, range 0-100), the mean increase was 12.3 (95% CI 11.1-13.6) points at 6 months. Significant improvements were found for fatigue (Fatigue Severity Scale, range 1-7): the mean decrease was -0.7 (95% CI -0.8 to -0.6) points at 6 months. However, severe fatigue was reported by 742/929 (79.9%) patients after 6 months. For physical functioning (Patient-Reported Outcomes Measurement Information System-Physical Function Short Form 10b, range 13.8-61.3), the mean increase was 5.9 (95% CI 5.9-6.4) points at 6 months. Mean differences of -0.8 (95% CI -1.0 to -0.5) points for anxiety (Hospital Anxiety and Depression Scale range 0-21) and -1.6 (95% CI -1.8 to -1.3) points for depression were found after 6 months. A worse baseline score, hospital admission, and male sex were associated with greater improvement between baseline and 6-month follow-up, whereas age, the BMI, comorbidities, and smoking status were not associated with mean changes in any outcome measures. CONCLUSIONS: Patients recovering from COVID-19 who receive primary allied health care make progress in recovery but still experience many limitations in their daily activities after 6 months. Our findings provide reference values to health care providers and health care policy makers regarding what to expect from the recovery of patients who receive health care from 1 or more primary allied health professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735744; https://tinyurl.com/3vf337pn. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2340/jrm.v54.2506.

Opioid prescribing in out-of-hours primary care in Flanders and the Netherlands: A retrospective cross-sectional study.

BACKGROUND: Increased opioid prescribing has raised concern, as the benefits of pain relief not always outweigh the risks. Acute and chronic pain is often treated in a primary care out-of-hours (OOH) setting. This setting may be a driver of opioid use but the extent to which opioids are prescribed OOH is unknown. We aimed to investigate weak and strong opioid prescribing at OOH primary care services (PCS) in Flanders (Northern, Dutch-speaking part of Belgium) and the Netherlands between 2015 and 2019. METHODS: We performed a retrospective cross sectional study using data from routine electronic health records of OOH-PCSs in Flanders and the Netherlands (2015-2019). Our primary outcome was the opioid prescribing rate per 1000 OOH-contacts per year, in total and for strong (morphine, hydromorphone, oxycodone, oxycodone and naloxone, fentanyl, tapentadol, and buprenorphine and weak opioids (codeine combinations and tramadol and combinations) and type of opioids separately. RESULTS: Opioids were prescriped in approximately 2.5% of OOH-contacts in both Flanders and the Netherlands. In Flanders, OOH opioid prescribing went from 2.4% in 2015 to 2.1% in 2017 and then increased to 2.3% in 2019. In the Netherlands, opioid prescribing increased from 1.9% of OOH-contacts in 2015 to 2.4% in 2017 and slightly decreased thereafter to 2.1% of OOH-contacts. In 2019, in Flanders, strong opioids were prescribed in 8% of the OOH-contacts with an opioid prescription. In the Netherlands a strong opioid was prescribed in 57% of these OOH-contacts. Two thirds of strong opioids prescriptions in Flanders OOH were issued for patients over 75, in the Netherlands one third was prescribed to this age group. CONCLUSION: We observed large differences in strong opioid prescribing at OOH-PCSs between Flanders and the Netherlands that are likely to be caused by differences in accessibility of secondary care, and possibly existing opioid prescribing habits. Measures to ensure judicious and evidence-based opioid prescribing need to be tailored to the organisation of the healthcare system.

Evaluation of Allied Healthcare in Patients Recovering from Covid-19: Study Protocol and Baseline Data of s National Prospective Cohort Study.

OBJECTIVE: To report the study protocol and baseline characteristics of a prospective cohort study to evaluate longitudinal recovery trajectories of patients recovering from COVID-19 who have visited a primary care allied health professional. DESIGN: Report of the protocol and baseline characteristics for a prospective cohort study with a mixed-methods approach. PATIENTS: Patients recovering from COVID-19 treated by primary care dietitians, exercise therapists, occupational therapists, physical therapists and/or speech and language therapists in the Netherlands. METHODS: The prospective study will measure primary outcome domains: participation, health-related quality of life, fatigue, physical functioning, and costs, at baseline, 3, 6, 9 and 12 months. Interviews, on the patients' experiences with allied healthcare, will be held with a subsample of patients and allied health professionals. RESULTS: The cohort comprises 1,451 patients (57% female, mean age 49 (standard deviation 13) years). Preliminary results for the study cohort show that 974 (67%) of the participants reported mild/moderate severity symptoms during the infection period and patients reported severe restrictions in activities of daily living compared with previous research in other patient populations. Both quantitative and qualitative, will provide insight into the recovery of patients who are treated by allied health professionals. CONCLUSION: In conclusion, this will be the first comprehensive study to longitudinally evaluate the recovery trajectories and related costs of patients recovering from COVID-19 who are treated by allied health professionals in the Netherlands. This study will provide evidence for the optimal strategy to treat patients recovering from COVID-19 infection, including which patients benefit, and to what extent, from treatment, and which factors might impact their recovery course over time. The preliminary results of this study demonstrated the severity of restrictions and complaints at the start of therapy are substantial.

Venous thromboembolism prophylaxis after total knee or hip replacement: treatment pattern and outcomes.

PURPOSE: To determine the thromboprophylactic treatment pattern and occurrence of venous thromboembolism (VTE), major bleeding, and wound infections in patients undergoing total knee replacement (TKR) or total hip replacement (THR). METHODS: From the PHARMO database, all patients ≥ 18 years hospitalized for TKR or THR between January 2003 and September 2008 were selected. Patients with pharmacy data up to 3 months after hospitalization were included in the study cohort. Duration and type of thromboprophylaxis were assessed. VTE, major bleeding, and wound infections were identified by hospitalizations. Regarding VTE, timing of event in relation to thromboprophylaxis was determined. RESULTS: The study population included 2930 patients with TKR, 5332 patients with THR without hip fracture, and 289 patients with THR and hip fracture. Mean duration of thromboprophylaxis was about 30 (± 20) days for all procedures, with low-molecular-weight heparin being the most frequently used drug. During 3 months of follow-up, 1% to 2% of patients were hospitalized for an event. The most observed event was wound infection (58%), followed by major bleeding (29%), and VTE (13%). For wound infection and major bleeding, median time after surgery was about 19 days. Median time between surgery and VTE was 24 days for TKR and 60 days for THR. Eighteen of 23 VTE occurred during thromboprophylaxis. CONCLUSIONS: Although patients are often treated for fewer days than recommended, thromboprophylaxis after TKR and THR in the Netherlands is adequate. Only 5 of 23 VTE hospitalizations occurred off-treatment and might have been prevented. Furthermore, fewer than 1% of patients were hospitalized for bleeding.

Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study.

Most studies investigating the association between psoriasis and cardiovascular disease have shown a significant relationship. This comparison study investigated the association between psoriasis and prevalent use of cardiovascular drugs. Drug exposure data for 1998 to 2006 were extracted from the Dutch PHARMO-Record Linkage System database. Psoriasis patients were selected using an algorithm of hospitalization and drug dispensing records specific for psoriasis and matched with controls for gender, age and time-period. From the records of 2.5 million Dutch residents, 9,804 (0.4%) psoriasis patients and 15,288 (0.6%) controls were selected. Psoriasis patients used significantly more anti-hypertensives, anti-coagulant and anti-platelet agents, digoxin, nitrates, lipid-lowering and anti-diabetic drugs than the reference population during a 5-year period observation. In a multiple linear regression model adjusting for the number of unique drugs used, psoriasis was no longer significantly associated with any of these drug classes. Psoriasis patients used more cardiovascular-related drugs, but surveillance bias appears to affect this association considerably.

Current issues around the pharmacotherapy of ADHD in children and adults.

BACKGROUND: New drugs and new formulations enter the growing market for ADHD medication. The growing awareness of possible persistence of ADHD impairment beyond childhood and adolescence resulting in increased pharmacotherapy of ADHD in adults, is also a good reason for making an inventory of the what is generally known about pharmacotherapy in ADHD. AIM: To discuss current issues in the possible pharmacotherapy treatment of ADHD in children, adolescents and adults with respect to the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used. METHODS: A search of the literature with an emphasis on the position of pharmacotherapy in ADHD treatment guidelines, the pharmacoepidemiological trends, and current concerns about the drugs used in pharmacotherapy. RESULTS: According to the guidelines, the treatment of ADHD in children consists of psychosocial interventions in combination with pharmacotherapy when needed. Stimulants are the first-choice drugs in the pharmacological treatment of ADHD in children despite a number of well known and frequently reported side effects like sleep disorders and loss of appetite. With regard to the treatment of adults, stimulant treatment was recommended as the first-choice pharmacotherapy in the single guideline available. Both in children and adults, there appears to be an additional though limited role for the nonadrenergic drug atomoxetine. The increase of ADHD medication use, in children, adolescents and in adults, can not only be interpreted as a sign of overdiagnosis of ADHD. Despite the frequent use of stimulants, there is still a lack of clarity on the effects of long-term use on growth and nutritional status of children. Cardiovascular effects of both stimulants and atomoxetine are rare but can be severe. The literature suggests that atomoxetine may be associated with suicidal ideation in children. CONCLUSION: Although pharmacotherapy is increasing common in the treatment of ADHD in both children and adults, there are still a lot of questions about side effects and how best to counter them. This suggests an important role for close monitoring of children and adults treated with stimulants or atomoxetine.

Challenging the challenge hypothesis on testosterone in fathers: Limited meta-analytic support.

In fathers testosterone levels are suggested to decrease in the context of caregiving, but results seem inconsistent. In a meta-analysis including 50 study outcomes with N = 7,080 male participants we distinguished three domains of research, relating testosterone levels to parental status (Hedges' g = 0.22, 95% CI: 0.09 to 0.35; N = 4,150), parenting quality (Hedges' g = 0.14, 95% CI: 0.03 to 0.24; N = 2,164), and reactivity after exposure to child stimuli (Hedges' g = 0.19, 95% CI: -0.03 to 0.42; N = 766). The sets of study outcomes on reactivity and on parenting quality were both homogeneous. Parental status and (higher) parenting quality were related to lower levels of testosterone, but according to conventional criteria combined effect sizes were small. Moderators did not significantly modify combined effect sizes. Results suggest that publication bias might have inflated the meta-analytic results, and the large effects of pioneering but small and underpowered studies in the domains of males' parental status and parenting quality have not been consistently replicated. Large studies with sufficient statistical power to detect small testosterone effects and, in particular, the moderating effects of the interplay with other endocrine systems and with contextual determinants are required.

Vasopressin Differentially Affects Handgrip Force of Expectant Fathers in Reaction to Own and Unknown Infant Faces.

The underlying mechanisms of paternal responses to infant signals are poorly understood. Vasopressin has previously been proposed to affect these responses. Using a double-blind, placebo-controlled, within-subject design (N = 25 expectant fathers), we examined the effect of vasopressin administration on the use of excessive handgrip force during exposure to infant crying versus matched control sounds, while participants saw morphed images representing their own infant versus an unknown infant. We found that, compared to placebo, AVP administration elicited more excessive force while viewing an unknown infant image compared to viewing the image representing one's own infant, while the reverse was true under placebo. The results are discussed in light of vasopressin's role in parenting and parental protection among human fathers.

Folic acid sensitive birth defects in association with intrauterine exposure to folic acid antagonists.

Since the protective effect of folic acid (FA) on birth defects is well known, it is reasonable to assume intrauterine exposure to FA antagonists increases the risk on these defects. We have therefore performed case-control analyses to investigate the risk of intrauterine exposure to FA antagonists, using data on births from the EUROCAT Northern Netherlands registry from 1997 to 2002. Of the 815 cases, 11 were exposed to a FA antagonist compared to 16 of the 1402 controls. For FA sensitive defects as a group, the study showed no effect after exposure to a FA antagonist (odds ratio (OR)=1.18, 95% CI: 0.55-2.57). We found no effect after exposure to a dihydrofolate reductase inhibitor (DHFRI) (OR 0.44, 95% CI: 0.12-1.54), but we did find a statistically significant effect after exposure to an antiepileptic drug (OR=3.45, 95% CI: 1.04-11.48). This study supports the findings of various other studies on the teratogenicity of antiepileptics. An association between DHFRIs and FA sensitive defects was not found.

Nature and management of duplicate medication alerts.

OBJECTIVE: To investigate the nature of duplicate medication (DM) alerts, their management by community pharmacists, and potential characteristics of DM alerts that lead to interventions by pharmacists. METHODS: Observational study in 53 community pharmacies. Each pharmacist registered the nature and management of 24 DM alerts on a structured form. RESULTS: On average, the clinical decision support systems generated 20.4 DM alerts per 100 dispensed drugs. In half of the 1272 registered alerts, the pharmacists judged that there was no risk for concurrent use of both prescriptions. In 32% of the alerts, the DM alert was generated for an intentional combination. In 17% of the alerts, there was a risk for unintentional concurrent use. In 32% of the alerts the pharmacists decided that one or more actions were needed: the electronic patient record was updated in 15% of the alerts and in 19% of the alerts the pharmacists performed an external action-for example, informing the patient or modifying the prescription (including 5 therapeutic prescription modifications and 22 logistic prescription modifications). Alerts concerning first dispensing were more likely to be followed by an external action than alerts concerning refills (40% vs 14%, P < .001). DISCUSSION AND CONCLUSION: In community pharmacy, prescription modifications based on DM alerts are rare, but DM alerts lead with some regularity to other actions-for example, patient instruction and update of the electronic patient record. As the current DM alerts are diverse and nonspecific in detecting situations where external action is considered relevant, other ways of alerting should therefore be considered.

Drug use by pregnant women and comparable non-pregnant women in The Netherlands with reference to the Australian classification system.

OBJECTIVE: To describe drug use in pregnancy, and compare drug use of pregnant women with non-pregnant women with respect to possible teratogenicity. STUDY DESIGN: A cross-sectional study based on pharmacy records from 1997 to 2001 was performed. Pregnant women and matched non-pregnant women (same physician and age) were identified. Prescriptions were set against the Australian risk classification. RESULTS: Thirty-five percent of all prescriptions for non-pregnant women were safe in pregnancy (Australian classification A), in 14% the risk was unknown (B1, B2), 49% were potentially harmful drugs (B3, C, D, X), and in 3% no classification was available. For pregnant women these figures were 86, 3, 10 and 2%, respectively. In non-pregnant women the highest percentages of prescriptions for unsafe drugs were for psycholeptics (99% not classified as safe), psychoanaleptics (100%), anti-inflammatory/antirheumetic products (100%), antihistamines (94%), antacids/anti-ulcer drugs (81%), antiepileptics (100%), beta-blockers (100%), systemic antimycotics (100%), antiprotozoals (97%), diuretics (100%) and immunosuppressives (100%). In pregnant women this pattern was comparable, except for antihistamines (22%) and antacids/anti-ulcer drugs (3%). CONCLUSION: We conclude that many drugs used by non-pregnant women should be avoided in pregnancy, and that pregnant women indeed do so. However, for some drug groups the available safe alternatives are limited.

Pharmacologic treatment of attention-deficit/hyperactivity disorder in children: incidence, prevalence, and treatment patterns in the Netherlands.

BACKGROUND: The prevalence of attention-deficit/hyperactivity disorder (ADHD) and the associated use of stimulant medications may have increased in the Netherlands in recent years, but there is a lack of data to confirm this trend. This retrospective analysis examined the incidence, prevalence, and treatment pattern of ADHD among children from a large sample representation of the general population of the Netherlands and represents the first such analysis in a large cohort of European children. OBJECTIVE: The aim of this study was to estimate the incidence and prevalence of children receiving initial pharmacotherapy for ADHD between 2000 and 2007 in the Netherlands and to describe treatment patterns (including persistence and adherence to ADHD medications) in this pediatric population. METHODS: Prescription and hospitalization data from the PHARMO medical record linkage system database in the Netherlands (2003 to 2006) were analyzed for patients with newly prescribed ADHD medication who were aged 6 to 17 years and received follow-up for at least 12 months after treatment initiation with methylphenidate, dexamphetamine, atomoxetine, or combination therapy. The yearly incidence and prevalence of children receiving ADHD pharmacotherapy were estimated for the period 2000 to 2007. Demographic characteristics and baseline medication data at treatment initiation were collected along with data on hospitalizations and psychotropic treatments in the year before initiation of ADHD treatment. RESULTS: Of the 4909 patients in the study cohort, 82% were male and 46% were between 6 and 9 years of age. The yearly incidence of children receiving ADHD medication--extrapolated from the PHARMO database to the Netherlands population--increased from 30 per 10,000 in the year 2000 to 75 per 10,000 in the year 2007. Prevalence rates showed a similar trend, increasing from 110 per 10,000 in 2000 to 210 per 10,000 in 2007. Prevalence and incidence rates both were consistently higher among boys than girls, although the greatest increases over time were observed in female patients. Analysis of treatment patterns revealed that most children (98%) initiated treatment with methylphenidate. Of those, 89% received an immediate-release formulation, although increased use of long-acting amphetamine and atomoxetine was apparent over the study period. Persistence and adherence rates varied according to the medications used and the prescribing physician. Antipsychotic agents and melatonin were the most commonly used therapeutics in the year before ADHD treatment initiation (6% and 4% of patients, respectively). CONCLUSIONS: The incidence and prevalence of children treated for ADHD increased from 2000 to 2007. Most children (98%) initiated treatment with immediate-release methylphenidate.