Prescription Registry Research Articles

Arterial Stiffness and Incident Glaucoma: A Large Population-Based Cohort Study

To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50 to 84 years. Prospective, population-based cohort study. Arterial stiffness was assessed in 4,713 participants without known glaucoma (mean ± SD age = 66 ± 8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles. During a mean ± SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95% CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95% CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95% CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95% CI 1.52-4.52; Ptrend = .007), ePWV (HR, 2.42, 95%CI 1.37-4.27; Ptrend = .03), and aPP (HR, 1.68, 95%CI 1.10-2.5; Ptrend = .02) were associated with the development of glaucoma. Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives.

Abstract PO3-01-14: Impact of detection mode, tumor characteristics and additional treatment on adherence to adjuvant endocrine therapy after breast cancer in Sweden

Abstract Background: Adjuvant endocrine therapy (AET) reduces recurrence and mortality in women with estrogen receptor (ER) positive early breast cancer (EBC). Adherence to AET has been shown to be lower than expected with risk of worse longtime prognosis. In a nationwide study in Sweden women with breast cancer diagnosis 2008-2010 adherence to AET at 5-year follow-up was estimated at 82,5% which is considered good related to recent published studies (manuscript is under review). Differences between regions and age-groups were shown. Present study investigates the impact on adherence of detection mode, tumor characteristics and additional treatment. Methods: Through the Swedish Cancer Registry (SCR) women with a first primary EBC diagnosed 2008-2010 were identified. From the Swedish National Breast Cancer Registry (NKBC) individual tumor and treatment data were collected. Included in the study was patients with ER positive tumors > 10 mm without distant metastasis at diagnosis. Through the Swedish Prescription Registry dispensed treatment from pharmacies was extracted and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥80%. Adherence at 3- and 5-year follow-up by detection mode, tumor characteristics and additional treatment was estimated. Results: Out of 21 016 women with a first primary BC 2008-2010 registered in the NKBC 10 176 met the inclusion criteria for the study. Among screen-detected tumors the 3- and 5-year adherence were 90,2 respectively 85,1% and 85,4 respectively 78,4% in the non-screen-detected group. In the screen-detected group the tumors were smaller and more often node negative. There was a significantly increased 5-year adherence in patients with stage III disease compared to those with stage I disease (84,1 vs 81,3 %) but not significant at 3-year (89,2 vs 87,3). Adjuvant chemotherapy significantly increased 3- (91.0% vs 85.8%) and 5-year (85.7% vs 79.3%) adherence among screen-detected and non-screen-detected respectively. Conclusions: Adherence to AET in Sweden was good, although there were differences depending on detection mode, tumor stage and additional adjuvant treatment. Stage and additional medical adjuvant treatment depend on each other and should not be seen as independent factors for adherence for AET. Citation Format: Anne Andersson, Anna Von Wachenfeldt, Lennarth Nyström, Frida Isaksson, Pihla Ruohonen. Impact of detection mode, tumor characteristics and additional treatment on adherence to adjuvant endocrine therapy after breast cancer in Sweden [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-14.

Symptomatic and Preventive Medication Use before and after Alzheimer's Disease Diagnosis: A 10-Year Matched Cohort Study

ObjectiveTo investigate longitudinal changes in symptomatic and preventive medication use among community-dwelling people with and without Alzheimer's disease (AD) 5 years pre- and post-AD diagnosis. DesignRetrospective matched cohort study. Settings and ParticipantsThe sample comprised 58,496 people with a geriatrician/neurologist-verified AD diagnosis matched 1:1 for age, sex, and region to people without AD in Finland. MethodsMedication dispensing data were obtained from the Finnish Prescription Register. Prevalence of symptomatic and preventive medication use was evaluated every 6 months from 5 years pre- to post-AD diagnosis. Longitudinal changes in medication use between people with and without AD were compared using ordinal logistic regression. ResultsDuring the 5 years pre- and post-diagnosis, there were differences in symptomatic (P < .001) and preventive (P = .006) medication use between people with and without AD. Over the 5 years pre-diagnosis, prevalence of symptomatic and preventive medications increased in both people with and without AD. During the 1 year pre-diagnosis, people with AD had a higher increase in use of ≥3 symptomatic medications (+4.4% vs +2.2%) and ≥3 preventive medications (+6.4% vs +2.9%) compared to people without AD. Over the 5 years post-diagnosis, symptomatic medication use plateaued in both people with and without AD. Meanwhile, people using ≥3 preventive medications decreased (−6.0%) in those with AD, but increased (+6.1%) in those without AD. During the follow-up period, people with AD had a larger absolute percentage increase in prevalence of antipsychotics (+22.7% vs +1.8%) and antidepressants (+19.1% vs +5.0%) than people without AD. During the same period, paracetamol and calcium supplement use increased by 31.1% and 20.4%, respectively, among people with AD. The largest absolute percentage decrease in prevalence of preventive medications over the 5 years post-diagnosis were beta-blockers (−9.8%) and statins (−7.0%) in people with AD. Conclusions and ImplicationsAt the point of and following diagnosis, there were population-level changes in medication use among people with AD. Medication assessments during this period appear to coincide with discontinuation of preventive medications whereas minimal changes were observed in symptomatic medication use.

Medication use among the oldest old in the Faroe Islands-A national cross-sectional study.

Aging is often associated with an increasing number of comorbidities that warrant use of multiple drugs which increases the use of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs) and drug-related problems (DRPs). The aim is to assess the prevalence of polypharmacy, PIMs, DDIs and DRPs among Faroese residents aged ≥90 years. In this population-based cross-sectional study, 494 individuals ≥90 years were invited and 298 (60%) participated. A pharmacist-led medication review was performed based on self-information, electronic patient journal and the Faroese Prescription Registry. The prevalence of polypharmacy was 74% with no sex-difference. Approximately 60% of participants used PIMs, primarily benzodiazepines and proton pump inhibitors, the latter being a frequently implicated medication in DRPs. Opioid use was low compared with other Nordic studies. DRPs were observed for 79% with discrepancies in the medication lists as the most common cause, and DDIs were identified for 47% of participants, mostly moderately clinically relevant DDIs. In conclusion, the medication use among the oldest old Faroese resembled that in other Nordic countries with a high prevalence of polypharmacy and use of PIMs, especially PPIs and benzodiazepines. However, no sex-difference was noted in medication use and the use of opioids was low.

Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Sleep Disorders and Sleep Disturbances in Persons with Multiple Sclerosis: A Population-Based Matched Case-Control Study in Denmark

Introduction: Adverse sleep is common in multiple sclerosis (MS). Population-based studies including adequate control groups are lacking. We hypothesized that the prevalence of sleep disorders and other sleep disturbances would be higher in persons with MS than in controls. Methods: We conducted a population-based study linking individual-level data from the Danish MS Registry (n = 21,943 persons with MS) and the Danish Population Registry (n = 109,715 matched controls) with information on sleep disorders from the Danish National Patient Registry and other sleep disturbances assessed by dispensed prescription drugs from the Danish National Prescription Registry. Results: Prevalence of diagnosed sleep disorders in terms of central hypersomnia (0.15% vs. 0.06%), sleep disturbances (1.05% vs. 0.70%), and sleep movements (0.22% vs. 0.13%) and other sleep disturbances identified by dispensed central acting (10.73% vs. 1.10%) and hypnotic use (30.65% vs. 20.13%) medication was statistically significantly higher among persons with MS when compared to controls. We found no statistically significant difference in the prevalence of sleep apnea and parasomnia between groups. Stratified by sex and age at MS diagnosis, results for differences between persons with MS and controls were similar. Conclusion: In this registry-based study, we found that the prevalence of several diagnosed sleep disorders was higher in persons with MS than in controls, that is, those reflecting insomnia and daytime symptoms including hypersomnia. Other sleep disturbances identified by dispensed prescription medication were markedly higher in persons with MS than in controls.

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study

PurposeMetronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. MethodsWe conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FindingsOut of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59–1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. ImplicationsOur findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

Seasonal Variations in Treatment Seeking for Alcohol Use Disorder in the Total Danish Population.

A minority of all individuals with alcohol use disorder (AUD) seek treatment. Contextual factors associated with treatment seeking are poorly understood. It is known that the level of alcohol consumed varies between seasons of the year. However, it is not known to what extent treatment seeking for AUD also varies between seasons. This study aims to investigate seasonal variations in treatment seeking for AUD. The study design was a time-series analysis. The study population consisted of adults age 18 years and older in Denmark seeking AUD treatment. The outcomes were the following two measures of changes in treatment seeking: (a) treatment entry and (b) filled prescription of AUD pharmacotherapy. Data came from the National Alcohol Treatment Register on treatment entries for specialist addiction care and National Prescription Registry for filled prescriptions on AUD pharmacotherapies from 2013 to 2018. Analysis was a segmented negative binomial regression. Treatment seeking for AUD showed clear seasonal variations, with the lowest numbers in December and from March to April. In January, treatment seeking was highest, with a decline around July and a subsequent slight rise from August to October. The findings emphasize the importance of contextual factors when developing and evaluating interventions to increase treatment seeking for AUD.

Paternal Preconceptional Alcohol Use Disorder With the Offspring's Mortality Risk

IntroductionPaternal pre-conceptional alcohol use may contribute to early pregnancy loss. However, the link between paternal pre-conceptional alcohol use disorder(AUD) and long-term offspring's mortality risk remains unclear. This study examined the association of paternal pre-conceptional AUD and recency of diagnosis with offspring's mortality, and further stratified the mortality after the first year of birth by age. MethodsThis is a nationwide cohort study with 1973174 Danish births(1980-2012), with follow-up from birth until death, emigration, or 31-December 2016. Paternal conceptional AUD was identified from Danish National Patient Register and Prescription Registry, categorizing recency of diagnosis into <1 year, 1-<4 years, 4-<8 years, ≥8 years. Logistic regression estimated odds ratios and 95% confidence intervals(CIs) for offspring mortality risk. All data were analyzed in 2023. ResultsPaternal pre-conceptional AUD was associated with a 28% increased mortality after one year of birth(95%CI=1.09-1.51), 23% increased infant mortality(95%CI=1.07-1.42), and 23% increased odds of stillbirth(95%CI=1.06-1.43). Paternal AUD diagnosed <1 year before conception was associated with an 85%-111% increased risk of mortality in offspring aged 15-40 years. More recent AUD diagnosis(i.e.,one year before conception) had a higher risks of death from infectious and circulatory diseases in offpring. ConclusionsOffspring of fathers with AUD before conception had higher mortality risk from birth to early adulthood, especially when AUD diagnosis is close to conception. Current awareness regarding paternal pre-conceptional alcohol dependence use is insufficient. Promoting alcohol dependence avoidance, including educating men on the impact of alcohol on child health during pre-pregnancy examination may help reduce or prevent long-term offspring mortality.

Sedative drug prescription patterns in Danish adults from 2002 through 2021. A register-based cohort study

ObjectivePharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. MethodsAll adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002–2006, 2007–2011, and 2012–2016. ResultsA total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012–2016. In 2002–2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011–2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. ConclusionSedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Patients with eosinophilic oesophagitis in Denmark have higher use of psychotropic drugs: A Danish nationwide study of psychotropic drug use in 3367 patients and 16,835 matched comparators.

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients. The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE. This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register. The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p≤0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE. Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders.

Breastfeeding decreases the risk of developing psoriasis through to early adulthood.

Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. To explore the role of early nutrition as a risk factor for the development of psoriasis. Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. Individuals breastfed for < 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective.

Polyautoimmunity in Patients With Anticyclic Citrullinated Peptide Antibody-Positive and -Negative Rheumatoid Arthritis: a Nationwide Cohort Study From Denmark.

This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative patients with rheumatoid arthritis (RA). In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP-positive vs anti-CCP-negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. The study included 5839 anti-CCP-positive and 3799 anti-CCP-negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP-positive and anti-CCP-negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP-negative patients developed autoimmune disease.

Maternal mental health disorders and offspring asthma and allergic diseases: The role of child mental health.

Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders. The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders. Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma. The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.

Apalutamide toxicity and tolerability: A real-world multicentre experience in metastatic hormone-sensitive prostate cancer (MHSPC) in the United Kingdom (UK).

107 Background: Apalutamide became available for mHSPC along with androgen deprivation treatment (ADT) in the UK in November 2021. We present here, to our best knowledge the first real world multicentre experience of Apalutamide use in mHSPC patients from three tertiary cancer centres from the UK. Our primary aim was to assess for toxicity and tolerability at this stage. Methods: We collected retrospective data from hospital prescription registries including all patients with mHSPC receiving Apalutamide between November 2021 and January 2023. Median period of follow up in our cohort was 14 months. Results: Two hundreds and ten patients received Apalutamide for mHSPC from three centres. The median age was 73 years. A total of 16.4% of the patients had recurrent mHSPC previously treated for localised PC and 83% were de novo metastatic. Of all patients, 43.3% had high-volume disease, and 56.7% had low-volume disease. The median presenting Prostate Specific Antigen (PSA) was 62 ng/l at diagnosis (range 0.87 to 5580). Undetectable PSA achieved in 43.3% of patient after starting Apalutamide and ADT. For those who have detectable PSA, median value was 0.22. Ninety percent of patients maintained their performance status (PS) at 0 or 1 on treatment. Most common side effects were fatigue (35.7%) and rash (11.4%). Cardiac adverse effects were recorded in 1.9% and thromboembolic events in 0.4%. Overall grade 3 and 4 toxicity was 5.2% across all symptoms assessed. To date, 83.3% patients continue on Apalutamide, 7.6 % discontinued due to toxicity and 9.1% had progressive disease (PD). Three deaths were recorded and all due to PD. Conclusions: In this multicentre retrospective analysis we found that Apalutamide and ADT is well tolerated in the real-world setting. Our patients are older and had lower volume metastasis compared with patients from the registry Trial (TITAN). Fatigue is more prevalent. Majority patients continue on Apalutamide with manageable side effects and good PS.

Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study.

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data. Meta-analyses across the five cohorts showed that PRS for schizophrenia was significantly positively associated with prescribed (standardized) antipsychotic dose (beta(SE) = 0.0435(0.009), p = 0.0006) and antipsychotic polypharmacy defined as taking ≥2 antipsychotics (OR = 1.10, CI = 1.05-1.21, p = 0.0073). The direction of effect was similar in all five independent cohorts. These findings indicate that genotypes may aid clinically relevant decisions on individual patients´ antipsychotic treatment. Further, the findings illustrate how real-world data have the potential to generate results needed for future precision medicine approaches in psychiatry.

Counting the costs: a nationwide study on healthcare use following an adalimumab biosimilar switch in >1300 inflammatory arthritis patients.

In Denmark, cost savings motivate mandatory biosimilar switches. In 2018, patients switched from originator to biosimilar adalimumab, that is, to GP2017 in Eastern and to SB5 in Western Denmark. However, concerns were raised about additional costs covering, that is, an increased number of outpatient visits due to patient education, treatment monitoring, and patient concerns. To investigate whether the switch led to increased total healthcare costs, defined as costs related to in- and outpatient contacts in hospitals and the primary sector and use of prescription medicine (excluding biological treatment). Observational cohort study with geographical cluster pseudo-randomization. Patients with rheumatoid arthritis, psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA), who switched were identified in the nationwide DANBIO registry. Total healthcare costs 9 months before and after the switch were captured from the National Patient and Prescription registries. The difference between pre- and post-switch costs was estimated by a generalized estimation equations (GEE) model. Overall, 1316 patients switched to GP2017 (n = 621) or SB5 (n = 695). Total healthcare costs were mainly driven by hospital costs. The monthly fluctuations of hospital costs 9 months before and after the switch were largely similar or decreased. In the adjusted analyses (GEE), hospital costs decreased after the switch (by approximately 15%) for GP2017 switchers, especially PsA (estimate = 0.83; 95% CI 0.75-0.92) and AxSpA patients (estimate = 0.85; 0.77-0.93), with no significant changes for SB5 switchers. We found no increase in total healthcare costs in 9 months following a nationwide mandatory adalimumab originator to biosimilar switch. Our findings were strengthened by similar results for GP2017 and SB5.

Arterial Thromboembolism in Patients With Atrial Fibrillation and CHA2DS2-VASc Score 1: A Nationwide Study.

Oral anticoagulation is suggested in patients with atrial fibrillation and a CHA2DS2-VASc score ≥1 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, and sex score). To assess granular differences within CHA2DS2-VASc 1, the incidence of arterial thromboembolism according to CHA2DS2-VASc 1 subgroups was examined. The Danish National Patient Registry and the Danish Prescription Registry were linked on a nationwide level to identify patients with atrial fibrillation from 2000 to 2021 without oral anticoagulation and categorized according to CHA2DS2-VASc score: CHA2DS2-VASc 0 (male and female subjects); CHA2DS2-VASc 1 (hypertension, heart failure, diabetes, vascular disease, and age 65-74 years); or CHA2DS2-VASc 2 (age ≥75 years without other risk factors). Female sex was not considered a risk factor in any risk group. The outcome was arterial thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Study groups were compared using Cox regression analysis. We included 26 701 patients with a CHA2DS2-VASc 0 score; 22 915 with CHA2DS2-VASc 1 (1483 patients with heart failure, 9066 with hypertension, 843 with diabetes, 770 with vascular disease, and 10 753 who were 65 to 74 years of age); and 14 525 patients with CHA2DS2-VASc 2 (≥75 years of age without other risk factors). With a median of 1 year of observation time, the cumulative incidence of arterial thromboembolism was 0.6% (n=154 [95% CI, 0.6%-0.8%]), 1.4% (n=16 [95% CI, 0.8%-2.2%]), 1.9% (n=141 [95% CI, 1.6%-2.2%]), 1.7% (n=12 [95% CI, 0.9%-2.9%]), 2.0% (n=13 [95% CI, 1.1%-3.4%]), 2.3% (n=187 [95% CI, 2.0%-2.7%]), and 4.4% (n=533 [95% CI, 4.1%-4.8%]) for CHA2DS2-VASc 0, heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years (CHA2DS2-VASc 1), and age ≥75 years (CHA2DS2-VASc 2), respectively. No statistically significant difference was identified among subgroups of CHA2DS2-VASc 1 (P=0.15 for difference). For patients with atrial fibrillation, all subgroups of CHA2DS2-VASc 1 were associated with lower incidence of arterial thromboembolism compared with age ≥75 years without other risk factors (ie, CHA2DS2-VASc 2) and a higher incidence compared with CHA2DS2-VASc 0. No statistically significant difference was identified between the subgroups of CHA2DS2-VASc 1. These findings support current recommendations that patients within this intermediate risk group could be identified with a similar risk of arterial thromboembolism.