General practitioners' and community pharmacists' beliefs and practices on opioids for non-malignant pain.

BACKGROUND: In Europe, opioid use has surged, largely due to prescriptions for chronic non-malignant pain (CNMP). General practitioners (GPs) and community pharmacists (CPs) play a major role in opioid prescribing for non-malignant pain. Exploring their personal beliefs and practices might reveal underlying mechanisms to identify measures that could halt the further escalation of opioid use. METHODS: Guided by the health belief model, a survey was designed and distributed nationwide to examine the practices and beliefs of GPs and CPs in the domains: threats, benefits, barriers and self-efficacy. The results of GPs and CPs were compared at the statement level using chi-square analysis. RESULTS: Of 214 GPs and 212 CPs who completed the survey, the majority agreed that too many opioids are used in the treatment of chronic non-malignant pain (66.8% GPs and 66.5% CPs). Furthermore, they were concerned about the addictive potential of opioids (83.1% GPs and 71.7% CPs). In general, both professions have concerns about opioid use. GPs report a slightly higher degree of self-efficacy and perceive fewer benefits from opioids in treating CNMP. GPs and CPs valued the recommended measures to reduce opioid prescribing, yet less than half actively implement these strategies in their clinics. CONCLUSION: GPs and CPs believe that opioids are being used too frequently to treat CNMP. However, both professions lack the actions to improve opioid-related care. GPs and CPs require education, collaboration and tools to implement guidelines on non-malignant pain and opioids. SIGNIFICANCE: This study, guided by the health belief model, reveals that general practitioners and community pharmacists have serious concerns about opioid use in chronic non-malignant pain. Despite shared concerns, both professions differ in their beliefs about opioid benefits and perceived self-efficacy. Both professions have in common that they value recommended measures to reduce opioid prescribing. Also, they both struggle to implement strategies, emphasizing the urgent need for education, collaboration and tools to align practices with guidelines on non-malignant pain and opioids.

Practice variation in opioid prescribing for non-cancer pain in Dutch primary care: A retrospective database study.

BACKGROUND: Prescription opioid use has increased steadily in many Western countries over the past two decades, most notably in the US, Canada, and most European countries, including the Netherlands. Especially the increasing use of prescription opioids for chronic non-cancer pain has raised concerns. Most opioids in the Netherlands are prescribed in general practices. However, little is known about variation in opioid prescribing between general practices. To better understand this, we investigated practice variation in opioid prescribing for non-cancer pain between Dutch general practices. METHODS: Data from 2017-2019 of approximately 10% of all Dutch general practices was used. Each year included approximately 1000000 patients distributed over approximately 380 practices. The primary outcome was the proportion of patients with chronic (>90 days) high-dose (≥90 oral morphine equivalents) opioid prescriptions. The secondary outcome was the proportion of patients with chronic (<90 oral morphine equivalents) opioid prescriptions. Practice variation was expressed as the ratio of the 95th/5th percentiles and the ratio of mean top 10/bottom 10. Funnel plots were used to identify outliers. Potential factors associated with unwarranted variation were investigated by comparing outliers on practice size, patient neighbourhood socioeconomic status, and urbanicity. RESULTS: Results were similar across all years. The magnitude of variation for chronic high-dose opioid prescriptions in 2019 was 7.51-fold (95%/5% ratio), and 15.1-fold (top 10/bottom 10 ratio). The percentage of outliers in the funnel plots varied between 13.8% and 21.7%. Practices with high chronic high-dose opioid prescription proportions were larger, and had more patients from lower income and densely populated areas. CONCLUSIONS: There might be unwarranted practice variation in chronic high-dose opioid prescriptions in primary care, pointing at possible inappropriate use of opioids. This appears to be related to socioeconomic status, urbanicity, and practice size. Further investigation of the factors driving practice variation can provide target points for quality improvement and reduce inappropriate care and unwarranted variation.

Indications related to antidepressant prescribing in the Nivel-PCD database and the SIDIAP database.

BACKGROUND: Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings. METHODS: A longitudinal study of new antidepressant users aged ≥65 was conducted, with data from the Nivel-PCD (The Netherlands) and SIDIAP (Catalonia) databases (2010-2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described. RESULTS: A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65-69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased. LIMITATIONS: It is not mandatory for physicians to register a diagnosis with each prescription. CONCLUSIONS: Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.

The influence of gender concordance between general practitioner and patient on antibiotic prescribing for sore throat symptoms: a retrospective study.

BACKGROUND: Patient gender as well as doctor gender are known to affect doctor-patient interaction during a medical consultation. It is however not known whether an interaction of gender influences antibiotic prescribing. This study examined GP's prescribing behavior of antibiotics at the first presentation of patients with sore throat symptoms in primary care. We investigated whether GP gender, patient gender and gender concordance have an effect on the GP's prescribing behavior of antibiotics in protocolled and non-protocolled diagnoses. METHODS: We analyzed electronic health record data of 11,285 GP practice consultations in the Netherlands in 2013 extracted from the Nivel Primary Care Database. Our primary outcome was the prescription of antibiotics for throat symptoms. Sore throat symptoms were split up in 'protocolled diagnoses' and 'non-protocolled diagnoses'. The association between gender concordance and antibiotic prescription was estimated with multilevel regression models that controlled for patient age and comorbidity. RESULTS: Antibiotic prescription was found to be lower among female GPs (OR 0.88, CI 95% 0.67-1.09; p = .265) and female patients (OR 0.93, 95% 0.84-1.02; p = .142), but observed differences were not statistically significant. The difference in prescription rates by gender concordance were small and not statistically significant in non-protocolled consultations (OR 0.92, OR 95% CI: 0.83-1.01; p = .099), protocolled consultations (OR 1.00, OR 95% CI: 0.68-1.32; p = .996) and all GP practice consultations together (OR 0.92, OR 95% CI: 0.82-1.02; p = .118). Within the female GP group, however, gender concordance was associated with reduced prescribing of antibiotics (OR 0.85, OR 95% CI: 0.72-0.99; p = 0.034). CONCLUSIONS: In this study, female GPs prescribed antibiotics less often than male GPs, especially in consultation with female patients. This study shows that, in spite of clinical guidelines, gender interaction may influence the prescription of antibiotics with sore throat symptoms.

[Inter-practice variation in polypharmacy prevalence amongst older patients in primary care]. / Bij iedere huisarts evenveel pillen?

PURPOSE: Complex medication management in older people with multiple chronic conditions can introduce practice variation in polypharmacy prevalence. This study aimed to determine the inter-practice variation in polypharmacy prevalence and examine how this variation was influenced by patient and practice characteristics. METHODS: This cohort study included 45,731 patients aged 55 years and older with at least one prescribed medication from 126 general practices that participated in NIVEL Primary Care Database in the Netherlands. Medication dispensing data of the year 2012 were used to determine polypharmacy. Polypharmacy was defined as the chronic and simultaneous use of at least five different medications. Multilevel logistic regression models were constructed to quantify the polypharmacy prevalence variation between practices. Patient characteristics (age, gender, socioeconomic status, number, and type of chronic conditions) and practice characteristics (practice location and practice population) were added to the models. RESULTS: After accounting for differences in patient and practice characteristics, polypharmacy rates varied with a factor of 2.4 between practices (from 12.4% to 30.1%) and an overall mean of 19.8%. Age and type of conditions were highly positively associated with polypharmacy, and to a lesser extent a lower socioeconomic status. CONCLUSIONS: Considerable variation in polypharmacy rates existed between general practices, even after accounting for patient and practice characteristics, which suggests that there is not much agreement concerning medication management in this complex patient group. Initiatives that could reduce inappropriate heterogeneity in medication management can add value to the care delivered to these patients.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.