Prescription Registry Research Articles

Early Life Oral Antibiotics Are Associated With Pediatric-Onset Inflammatory Bowel Disease-A Nationwide Study.

Early-life environmental triggers are thought to play a larger role in pediatric-onset inflammatory bowel disease (pIBD) compared to adult-onset IBD. We aimed to assess the risk of developing pIBD after exposure to oral antibiotics during the first 5 years of life. In a nation-wide cohort study, we identified all patients diagnosed with pIBD (<18 years at diagnosis) in Denmark between 1995 and 2018 from the National Patient Registry and matched them with up to 10 reference individuals. Antibiotic exposure was defined as being prescribed antibiotics during first 5 years of life. Data were retrieved from the National Prescription Register. Outcome was developing pIBD. Risk estimates are presented by hazard ratios (HR) with 95% confidence intervals (CI). We identified 1927 pIBD patients and 18,318 reference individuals. Oral antibiotic exposure during the first 5 years of life was associated with a higher risk of developing pIBD (HR = 1.33 [95% CI: 1.2-1.5], P <0.0001). The risk was also increased if patients had ≥4 antibiotic prescriptions compared to no antibiotics (HR = 1.33 [95% CI: 1.2-1.5], P <0.0001). Broad-spectrum antibiotics increased the risk of pIBD compared to narrow-spectrum antibiotics (HR = 1.29 [95% CI: 1.2-1.4], P < 0.0001). When stratified by IBD subtypes, only Crohn disease was significantly associated with exposure to antibiotics (HR = 1.37 [95% CI: 1.1-1.7], P = 0.002). In this nationwide registry-based study, we found that oral antibiotic exposure during first 5 years of life was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates.

Impact of the publication of the Finnish Meds75+ database on the use of potentially inappropriate medications in older persons.

To evaluate the impact of the updated nationwide Meds75+ database and its linkage to the Finnish health portal on the use of potentially inappropriate medications (PIMs) among older persons. We also aimed to evaluate whether there is regional variation in trend changes of PIM use. Meds75+ was implemented at the population level in 2015, so randomization is unfeasible. We used a quasi-experimental interrupted time series analysis to evaluate the changes in levels and trends of PIM use. The data included all Finnish community-dwelling persons aged ≥75 years (N = 920 163) who had medication purchases in the Prescription Register during 2009-2020. Data were linked with the Care Registers for Health and Social Care and the cause of death register. The prevalence of PIMs decreased from 20.2% in 2009 to 11.7% in 2020. The change of level of the monthly PIM users was negative (β -0.036, 95% confidence interval [CI] -0.202 to 0.131), but not statistically significant (P = .673) after the publication of the database. We found a small decrease (β -0.018, 95% CI -0.083 to 0.047, P = .593) in the slope of PIM users, but it was not statistically significant. The regional results were similar to the main findings. Publication of the updated Meds75+ database did not decrease the level or trend of PIM users. In addition, this study did not show any significant regional variation in PIM use trends. Further research should focus on determining barriers and facilitators to the utilization of PIM criteria in clinical practice.

Does attendance in outdoor kindergartens reduce the use of antibiotics in children?

To determine whether children enrolled in rural outdoor kindergartens had a lower risk of redeeming at least one prescription for antibiotics compared to children enrolled in urban conventional kindergartens, and if type of antibiotics prescribed differed according to kindergarten type. Two Danish municipalities provided data including civil registration numbers from children enrolled in a rural outdoor kindergarten in 2011-2019, and a subsample of all children enrolled in urban conventional kindergartens in the same period. Civil registration numbers were linked to individual-level information on redeemed prescriptions for antibiotics from the Danish National Prescription Registry. Regression models were performed on 2,132 children enrolled in outdoor kindergartens, and 2,208 children enrolled in conventional kindergartens. There was no difference between groups in risk of redeeming at least one prescription for all types of antibiotics (Adjusted Risk Ratio: 0.97 (95% Confidence Intervals 0.93,1.02, p=0.26)). Similarly, there were no differences between kindergarten type and risk of redeeming at least one prescription for systemic, narrow-spectrum systemic antibacterial, broad-spectrum systemic antibacterial, or topical antibiotics. Compared to children who were enrolled in conventional kindergartens, children who were enrolled in outdoor kindergartens did not have a lower risk of redeeming prescriptions for any type of antibiotics.

#2976 CHRONIC KIDNEY DISEASE WITH COMORBIDITY IN PRIMARY CARE: CARDIORENAL TREATMENT, QUALITY OF CARE AND PROGNOSIS

Abstract Background and Aims Diabetes, heart failure, hypertension and cardiovascular disease are common in primary care, and frequently coexist with impaired kidney function (CKD), further increasing risk of cardiovascular- and renal events as well as premature death. These comorbidities therefore call for more complex treatment regimens and monitoring. Our aim was to describe the prevalence, management, and prognosis of individuals with CKD and additional comorbidity in a large primary care cohort. Method Individuals were included from the Copenhagen Primary Care Laboratory (CopLab) Database, which contains 112 million biochemistry results from persons followed in primary care between 2000 and 2015 and divided into three groups based on (CKD-EPI) eGFR (&amp;gt;60 ml/min, 30-59 ml/min and &amp;lt;30 ml/min) with or without comorbidity in the form of diabetes or heart failure. We included all individuals with at least two measurements of creatinine. The date of the second measurement of creatinine was considered index date (baseline). The database has been combined with pharmacological data (The Danish National Prescription Registry), outpatient clinic visits and hospitalizations (The Danish National Patient Registry - NPR), and mortality information (The Danish Civil Registration System). Heart Failure was defined by ICD-codes in NPR from outpatient clinic visits and hospitalizations and we calculated crude event rates for a range of outcomes according to comorbidity. Diabetes was defined as at least one measurement of plasma or serum glucose ≥11 mmol/l or HbA1c ≥48 mmol/mol in CopLab. We evaluated monitoring of eGFR, albuminuria (UACR) and use of guideline-recommended pharmacological therapy (i.e. RAS-blockers and statins) in each group. Results In the total primary care population of 171,134 individuals of which 63.8% were female, 8.3% had impaired kidney function (eGFR&amp;lt;60ml/min). The median follow-up for the three eGFR groups was 8.4, 4.7 and 2.0 years, respectively. Overall, event rates were higher in individuals with impaired kidney function and comorbidity, i.e. mortality in the group with eGFR&amp;lt;30 ml/min with concurrent heart failure; 42.8 per 100 patient-years (PY). Event rates for ESKD were low in general (0.03 to 0.51 per 100 PY) except for individuals with eGFR&amp;lt;30 ml/min (2.1 to 3.5 per 100 PY). Annual monitoring of eGFR was high in all groups (&amp;gt;90%) with increasing frequency in individuals with impaired kidney function, and measurement of UACR was low in groups with non-diabetic CKD (10-30%). Antihypertensive treatment was frequently prescribed in eGFR &amp;lt;30 ml/min; overall 87.6% and 94.8% with coexisting diabetes and 92.8% with coexisting heart failure. The use of RAS inhibition was more used in diabetes and in heart failure (&amp;gt;50%) but less with low eGFR. Statin therapy was used in approximately 50% of individuals with diabetes, regardless of CKD group, but was used to a much less extent in non-diabetic CKD (20-24%). Conclusion Our data from a large primary care cohort demonstrate a high prevalence of coexisting diabetes and/or heart failure with CKD, increasing the risk for adverse outcomes. The quality of CKD care in general practice may be improved, especially in the non-diabetic population.

Risk and protective factors in Parkinson's disease: a simultaneous and prospective study with classical statistical and novel machine learning models.

Several environmental/lifestyle factors have been individually investigated in previous Parkinson's disease (PD) studies with controversial results. No study has prospectively and simultaneously investigated potential risk/protective factors of PD using both classical statistical and novel machine learning analyses. The latter may reveal more complex associations and new factors that are undetected by merely linear models. To fill this gap, we simultaneously investigated potential risk/protective factors involved in PD in a large prospective population study using both approaches. Participants in the Moli-sani study were enrolled between 2005 and 2010 and followed up until December 2018. Incident PD cases were identified by individual-level record linkage to regional hospital discharge forms, the Italian death registry, and the regional prescription register. Exposure to potential risk/protective factors was assessed at baseline. Multivariable Cox Proportional Hazards (PH) regression models and survival random forests (SRF) were built to identify the most influential factors. We identified 213 incident PD cases out of 23,901 subjects. Cox PH models revealed that age, sex, dysthyroidism and diabetes were associated with an increased risk of PD. Both hyper and hypothyroidism were independently associated with PD risk. SRF showed that age was the most influential factor in PD risk, followed by coffee intake, daily physical activity, and hypertension. This study sheds light on the role of dysthyroidism, diabetes and hypertension in PD onset, characterized to date by an uncertain relationship with PD, and also confirms the relevance of most factors (age, sex, coffee intake, daily physical activity) reportedly shown be associated with PD. Further methodological developments in SRF models will allow to untangle the nature of the potential non-linear relationships identified.

Comorbidity in Congenital Hypothyroidism-A Nationwide, Population-based Cohort Study.

Patients with congenital hypothyroidism (CH) are affected more often than the general population by other chronic diseases and neurological difficulties. The aim of this nationwide population-based register study was to investigate the incidence of congenital malformations, comorbidities, and the use of prescribed drugs in patients with primary CH. The study cohort and matched controls were identified from national population-based registers in Finland. All diagnoses from birth until the end of 2018 were collected from the Care Register, and subject-specific prescription drug purchases were identified from The Prescription Register from birth until the end of 2017. Diagnoses of neonatal and chronic diseases were collected for 438 full-term patients and 835 controls (median follow-up time 11.6 years; range, 0-23 years). Newborns with CH were more often found to have neonatal jaundice (11.2% and 2.0%; P < .001), hypoglycemia (8.9% and 2.8%; P < .001), metabolic acidemia (3.2% and 1.1%; P = .007), and respiratory distress (3.9% and 1.3%; P < .003) as compared to their matched controls.Congenital malformations were diagnosed in 66 of 438 (15.1%) CH patients and in 62 of 835 (7.4%) controls (P < .001). The most commonly affected extrathyroidal systems were the circulatory and musculoskeletal systems. The cumulative incidence of hearing loss and specific developmental disorders was higher among CH patients than controls. The use of antidepressant and antipsychotic drugs was similar in CH patients and their controls. CH patients have more neonatal morbidity and congenital malformations than their matched controls. The cumulative incidence of neurological disorders is higher in CH patients. However, our results do not support the existence of severe psychiatric comorbidity.

POSITIVE ASSOCIATION BETWEEN BASELINE ARTERIAL STIFFNESS AND NEW-ONSET DIABETES: A POPULATION-BASED COHORT STUDY

Objective: The temporal relationship between increased arterial stiffness and diabetes remains unclear. This study aimed to investigate whether arterial stiffness was associated with new-onset diabetes. Design and method: The study population comprised participants from the Vitamin D Assessment (ViDA) Study, a randomised controlled trial of vitamin D supplementation that recruited participants mostly from family practices in Auckland, New Zealand from 5 April 2011 to 6 November 2012. Arterial stiffness was measured at baseline by aortic pulse wave velocity (aPWV), augmentation index (AIx) and pulse pressure (PP). Vitamin D did not affect the risk of the main study outcomes including cardiovascular disease. The final study population was 4479 participants after excluding those with existing diabetes (as determined by dispensed prescriptions and self-report). New-onset diabetes was determined by linkage to dispensed prescription and national hospital discharge registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to aPWV, AIx and PP. Results: The mean (SD) age of participants at baseline was 66.2 (8.3), 2556 (57.1%) were male and 3880 (86.6%) were of European or other ethnicity, with the remainder being Polynesian (including indigenous Maori) or South Asian. During a mean (SD) follow-up of 6.86 ± 0.43 years, 364 (8.1%) participants developed diabetes. Following adjustment for age, sex, ethnicity, mean arterial pressure, body mass index and vitamin D supplementation (vitamin D vs placebo), aPWV and PP, but not AIx were associated with an increase in new onset-diabetes (per SD increase, aPWV hazard ratio, 1.36, 95% CI, 1.13 to 1.64; PP hazard ratio, 1.40 95% CI, 1.16 to 1.68; AIx hazard ratio, 1.02, 95% CI, 0.91 to 1.14). Conclusions: Arterial stiffness, as measured by aPWV and PP, independent of other risk factors, may be a useful predictor of new-onset diabetes.

Trends in the use of psychotropics in older people with dementia: interrupted time series of Finnish clinical guidelines of behavioural and psychological symptoms of dementia.

Up to 90% of people with dementia experience behavioural and psychological symptoms of dementia (BPSD) as part of their illness. Psychotropics are not recommended as the first-line treatment of BPSD because older people are more prone to adverse reactions. In this study, we evaluate the impact of the Finnish clinical guidelines of BPSD (published in 2017) on psychotropic use in people with dementia. This study is based on Finnish Prescription Register data from 2009 to 2020. The data included all community-dwelling Finnish people aged ≥65 and who had anti-dementia medication purchases (n= 217,778). We used three-phased interrupted time series design to evaluate the changes in levels and trends of monthly (n= 144) psychotropic user rates compared with the predicted trends. In addition, we evaluated the changes in levels and trends of monthly new psychotropic user rates. The level of monthly psychotropic user rate decreased non-significantly during the intervention period (β -0.057, P= 0.853), and during the post-intervention period, there was an increase in the level (β 0.443, P= 0.091) and slope (β 0.199, P= 0.198), but not statistically significant. The level of monthly new psychotropic user rate (β -0.009, P= 0.949) during the intervention period and the level (β 0.044, P= 0.714) and slope (β 0.021, P= 0.705) during the post-intervention period were almost unchanged. Results may indicate possible challenges in deprescribing and better adherence to the guidelines at the beginning of BPSD treatment. Further research into the barriers to implement BPSD guidelines and the availability of non-pharmacological treatments is needed.

The impact of an annual mass media campaign on treatment seeking for alcohol use disorders in the Danish population: An interrupted time-series analysis

IntroductionA minority of individuals with alcohol use disorder (AUD) seek treatment. In Denmark, a mass media campaign, “RESPEKT”, aiming to increase treatment seeking, has been broadcasted nationwide since 2015. The campaign is unique from an international perspective. Similar interventions have, up until now, not been scientifically evaluated. AimTo investigate whether there was an association between campaign periods and treatment seeking for AUD. A secondary aim was to investigate possible gender differences. The hypotheses were that treatment seeking would increase during the campaign periods, and that men would increase their treatment seeking more compared to women. MethodStudy design: Interrupted time-series analysis.Participants: Adults aged 18 years and above in the Danish population seeking AUD treatment.Exposure: Campaign periods year 2015–2018.Outcome: Changes in treatment seeking defined as treatment entry respectively filled prescription of AUD pharmacotherapy.Data: National Alcohol Treatment Register on treatment entries for specialist addiction care and National Prescription Registry for filled prescriptions on AUD pharmacotherapies 2013–2018.Analysis: Segmented negative binomial regression, including the full cohort and stratified by sex. ResultsThe results show no association between campaign periods and treatment seeking. Nor were there any gender differences in treatment seeking. The hypotheses were not confirmed. ConclusionThe campaign periods showed no association with treatment seeking. Eventual future campaigns should possibly focus on earlier steps of the treatment seeking process, as problem recognition, to increase treatment seeking. There is a great need to develop other ways to narrow the treatment gap for AUD.

Prenatal opioid exposure and risk of asthma in childhood: a population-based study from Denmark, Norway, and Sweden.

Background: Opioids may modulate the immune function through opioid receptors on immune cells. Long-term consequences of prenatal opioid exposure on the immune system, such as childhood asthma, are unknown. Objectives: To investigate whether prenatal opioid exposure is associated with the risk of childhood asthma. Methods: Cohort study using linked nationwide registers in Denmark (1996-2015), Norway (2005-2015), and Sweden (2006-2013). Children born by mothers who were chronic opioid analgesics users before pregnancy (n = 14,764) or who were receiving opioid maintenance therapy (OMT) before or during pregnancy (n = 1,595) were identified based on information from each of the medical birth registers and prescription registers. Long-term opioid analgesics exposed children were compared to short-term exposed or unexposed, whereas OMT exposed children were compared to OMT unexposed. Asthma among children ≥1years of age was defined as two or more filled prescriptions of antiasthmatic medication within 365days, or a diagnosis of asthma. Hazard ratios (HRs) were calculated using Cox proportional hazards regression with attained age as the time scale. Inverse probability of treatment weights based on propensity scores were applied to adjust for measured confounders. Individual level data from Norway and Sweden were pooled, whereas individual level data from Denmark were analyzed separately. For the opioid analgesics comparisons, adjusted HRs (aHR) from the combined Norwegian/Swedish data and the Danish data were pooled in a fixed-effects meta-analysis. Results: For the opioid analgesics cohort, no increased risk of asthma was observed in long-term exposed children neither compared with unexposed [aHR = 0.99 (95% CI 0.87-1.12)], nor compared with short-term exposed [aHR = 0.97 (0.86-1.10)]. No increased risk of asthma was observed in OMT exposed compared with OMT unexposed children [Norway/Sweden: aHR = 1.07 (0.60-1.92), Denmark: aHR = 1.25 (0.87-1.81)]. Results from sensitivity analyses, where potential misclassification of the outcome and misclassification of OMT exposure were assessed, as well as starting follow-up at 6years of age, showed that the estimates of association were generally robust. Conclusion: We found no association between prenatal exposure to opioids and risk of childhood asthma. Results were consistent across two different opioid exposure groups with different confounder distributions.

Genetic analysis of probable sleep bruxism and its associations with clinical and behavioral traits.

Sleep bruxism (SB) can cause damage on teeth, headache and severe pain affecting both sleep and daily functioning. Yet despite the growing interest into bruxism, the underlying clinically relevant biological mechanisms remain unresolved. The aim of our study was to understand biological mechanisms and clinical correlates of SB including previously reported disease associations. We used data from the FinnGen release R9 (N = 377 277 individuals) that are linked with Finnish hospital and primary care registries. We identified 12 297 (3.26%) individuals with International Classification of Diseases (ICD)-10 codes used for SB. In addition, we used logistic regression to examine the association between probable SB and its clinically diagnosed risk factors and comorbidities using ICD-10 codes. Furthermore, we examined medication purchases using prescription registry. Finally, we performed the first genome-wide association analysis for probable SB and computed genetic correlations using questionnaire, lifestyle, and clinical traits. The genome-wide association analysis revealed one significant association: rs10193179 intronic to Myosin IIIB (MYO3B) gene. In addition, we observed phenotypic associations and high genetic correlations with pain diagnoses, sleep apnea, reflux disease, upper respiratory diseases, psychiatric traits, and also their related medications such as antidepressants and sleep medication (p < 1e-4 for each trait). Our study provides a large-scale genetic framework to understand risk factors for SB and suggests potential biological mechanisms. Furthermore, our work strengthens the important earlier work that highlights SB as a trait that is associated with multiple axes of health. As part of this study, we provide genome-wide summary statistics that we hope will be useful for the scientific community studying SB.

Preconception use of antibiotics and fecundability: a Danish prospective cohort study

To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). Not applicable. 9462 female participants, median age 29 years at enrollment. Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

Treatment of High Blood Pressure is associated with a Reduced Incidence of Parkinson’s disease (S42.007)

<h3>Objective:</h3> We performed an agnostic drug-wide association study (DWAS) in Norway estimating the association between all drugs prescribed in Norway and the subsequent incidence of Parkinson’s disease (PD). <h3>Background:</h3> Several drugs including treatments for cardiovascular diseases have been associated with a reduced incidence of PD. <h3>Design/Methods:</h3> We employed data on drug use in the entire Norwegian population from 2004 to 2019 (4.6 million) registered in the Norwegian Prescription Registry, including more than 600 million individual prescriptions. Drug classes were screened according to ATC codes at level 2, corresponding to therapeutic subgroups. Individuals who developed PD during the 15 years of follow-up (n=15,849) were identified using an algorithm based on drugs prescribed to treat the disease. Cox regression models with exposure as time-dependent variable were specified, and all p-values were corrected for multiple testing using the false discovery rate. <h3>Results:</h3> We found several novel associations between drug classes and the incidence of PD including a <i>decreased</i> incidence of PD among users of drugs acting on the renin-angiotensin system (0.86, 95%CI: 0.83–0.89). We also found an inverse association between calcium channel blockers and PD incidence, but we could not confirm the previously reported association between lipid-modifying agents and PD. Further, beta blocking agents and drugs for cardiac therapy were associated with an <i>increased</i> PD incidence. We also found increased PD incidence for drugs used in the treatment of prodromal symptoms of PD, including urologicals, drugs for constipation, anti-psychotics, and antidepressants. <h3>Conclusions:</h3> We observed two large drug classes of anti-hypertensives being associated with a subsequent reduced incidence of PD. The finding of two other cardiovascular drug classes being associated with an <i>increased</i> PD incidence calls for more detailed epidemiological studies and experimental studies to elucidate possible mechanisms. <b>Disclosure:</b> Trond Riise has nothing to disclose. Mr. Solheim has nothing to disclose. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Igland has nothing to disclose. Miss Tuominen has nothing to disclose. Dr. Abolpour Mofrad has nothing to disclose. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. Dr. Scherzer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Scherzer has received research support from NIH. The institution of Dr. Scherzer has received research support from Michael J. Fox Foundation. The institution of Dr. Scherzer has received research support from American Parkinson’s Disease Association. Dr. Scherzer has received intellectual property interests from a discovery or technology relating to health care. Mrs. Romanowska has nothing to disclose.

Agreement between survey- and register-based measures of depression in Denmark.

Register-based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey- and register-based measures of depression, and explored sociodemographic and health-related factors that may have influenced this agreement. All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records. A checklist for depressive symptoms within the last 14 days (Major Depression Inventory; MDI) from the survey was compared with register-based assessment of hospital-diagnosed MDD and/or prescriptions for antidepressants. We estimated agreement between survey-based and register-based measures for depression and used logistic regression models to explore selected associated factors. In total, 5.9% of How are you? survey participants screened positive for current depression on the MDI. Of these, 51.3% (95% confidence interval (CI): 49.0-53.6) filled a prescription for an antidepressant medication during the 10 years prior or 2 years following the administration of the survey, and 14.5% (95% CI: 12.9-16.2) were treated for MDD in a psychiatric hospital-based setting. When using a higher threshold of the MDI indicating more severe current depression, 22.8% (95% CI: 19.6-26.1) of those who screened positive also received an MDD diagnosis and 63.4% (95% CI: 59.7-67.2) were prescribed antidepressants during this 12-year period. Among those with current depression, female sex, older age, chronic diseases, hospital-treated self-harm, and being permanently outside the workforce were associated with having a register-based MDD diagnosis or antidepressant prescription. Among those with a register-based depression record, female sex, younger age, hospital-treated self-harm, stress, and severe loneliness were associated with current depression. We found that as few as 15% of individuals with current depression in the general Danish population were captured by the psychiatric hospital register, while 51% of these individuals were identifiable in the prescription register. These findings demonstrate that register-based measures significantly underestimate the true prevalence of depression by identifying only the cases that are most severe.

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions

BackgroundImplant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called “breast implant illness” (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. MethodsThe Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DiscussionThe Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. RegistrationThis study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Incidence of gastrointestinal malignancies increases in persons received eradication therapy for Helicobacter pylori: A cohort study.

Long-term Helicobacter pylori infection increases the risk of gastric malignancies. Since the symptoms for H. pylori gastritis, as well as for several malignancies, may be nonexisting or highly unspecific, even H. pylori-positive subjects with underlying malignancies may receive eradication therapy. The aim was to assess the incidence of gastrointestinal and various other malignancies in individuals after eradication therapy for H. pylori infection. A cohort of 217,554 subjects (120,344 women and 97,210 men), who had purchased specific combinations of drugs for H. pylori eradication therapy in 1994-2004, was identified by the Finnish National Prescription Registry and followed for cancer incidence until the end of 2008 (1.89 million person-years at risk). A total of 22,398 malignancies were identified in the cohort. In both genders, for the first 6 months after drug prescription, the standardized incidence ratios (SIRs) were between 5 and 32 for gastric, colorectal, and pancreatic cancers, and 2 and 3 for several other malignancies. Although later on the SIRs of most malignancies fell rapidly, those of gastric noncardia and lung cancers remained elevated up to 5 years of follow-up. The only SIRs below unity were seen in men for gastric cancers (cardia 0.61, 95% CI: 0.37-0.95; intestinal noncardia 0.74, 95% CI: 0.56-0.97) during the post-therapy period covering years 5-15. Incidence levels significantly above the population rates were detected for many malignancies. Although eradication of H. pylori may have a long-lasting protective effect against gastric cancer, H. pylori therapy may postpone the detection of malignancies possibly underlying unspecific gastrointestinal symptoms. Therefore, it should be emphasized that the diagnostic work-up for malignancies should not be stopped in case of detection and treatment of H. pylori infection.

Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study

ObjectivesTo examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled.DesignRetrospective...

Incidence and prognosis of superficial vein thrombosis during pregnancy and the post-partum period: a Danish nationwide cohort study

The incidence of superficial vein thrombosis (SVT) of the legs and the subsequent risk of venous thromboembolism during pregnancy and the post-partum period is unknown. To better understand the clinical course of SVT during these times, we aimed to estimate the incidence rate of SVT during pregnancy and in the post-partum period, as well as the risk of subsequent venous thromboembolism. In this nationwide cohort study, we collected data on all pregnant women who delivered between Jan 1, 1997, and Dec 31, 2017, in Denmark were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Prescription Registry. Data on ethnicity were not available. Incidence rates per 1000 person-years were calculated for each trimester and the antepartum and post-partum period. Among women with a pregnancy-related SVT, risk of subsequent venous thromboembolism within the same pregnancy or post-partum period were calculated and compared with a matched cohort of pregnant women without SVT using Cox proportional hazards analysis. During 1 276 046 deliveries, 710 diagnoses of lower extremity SVT occurred from conception up to 12 weeks postpartum (0·6 per 1000 person-years [95% CI 0·5-0·6]). The incidence rates of SVT per 1000 person-years were 0·1 (95% CI 0·1-0·2) during the during the first trimester, 0·2 (0·2-0·3) during the second trimester, and 0·5 (0·5-0·6) during the third trimester. The incidence rate was 1·6 per 1000 person-years (95% CI 1·4-1·7) during the post-partum period. Of the 211 women with antepartum SVT included in the analysis, 22 (10·4%) were diagnosed with venous thromboembolism, compared with 25 (0·1%) in women without SVT (hazard ratio 83·3 [95% CI 46·3-149·7]). The incidence rate of SVT during pregnancy and the post-partum period was low. However, if SVT during pregnancy was diagnosed, the risk of developing venous thromboembolism during the same pregnancy was high. These results might help physicians and patients to make decisions about anticoagulant management of pregnancy-related SVT. None.

Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway

Approximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum. To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes. This cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy. Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method. Initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models. Among 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found. Based on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found. These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.

Abstract P3-03-10: The Impact of Type 2 Diabetes on Complications after Primary Breast Cancer Surgery: a Danish population-based cohort study

Abstract Introduction Type 2 diabetes (T2D) is associated with obesity and other comorbidities involving multiple organ systems, which may increase the risk of postsurgical complications. Knowledge is sparse on the impact of T2D on the postsurgical outcome after breast cancer (BC) surgery in primary BC. Objectives To investigate the association of T2D and risk of complications after primary BC surgery, and according to neoadjuvant chemotherapy. Methods Our cohort included all Danish women diagnosed with early-stage operable BC during 1996-2018 registered in the Danish Breast Cancer Group clinical database. All patients had primary surgical treatment—mastectomy or breast conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries, defining T2D via diagnostic codes or redemption of ≥2 prescriptions for glucose-lowering drugs. We defined postoperative complications as hospital admissions for medical or surgical complications (re-operations (excluding seromas), bleeding, infection, thrombosis, kidney or arterial cardiovascular disease) up to 30 days after primary BC surgery. We calculated the 30-day cumulative incidence function (CIF) of postoperative complications and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (95% CI) overall, and stratified by the receipt of neoadjuvant chemotherapy, adjusting for potential confounders. Results Among 84,491 women with operable BC, 4,669 (5.5%) had prevalent T2D at time of BC surgery. Overall, 800 (17.1%) and 8,621 (10.8%) of BC patients with and without T2D developed postoperative complications corresponding to CIFs of 17% (95%CI: 16% - 18%) and 11% (95%CI: 10% - 11%), respectively, and a HR of 1.44 (95%CI: 1.34-1.56). 173 (3.7%) BC patients with T2D and 2,805 (3.5%) without T2D received neoadjuvant chemotherapy. Among those who did not receive neoadjuvant chemotherapy, the CIFs of postoperative complications was 17% (95% CI: 16% - 18%) and 11% (95% CI: 10% - 11%) for women with and without T2D, respectively, with a corresponding HR of 1.42 (95% CI: 1.31-1.53). For those with and without T2D who received neoadjuvant chemotherapy, the CIFs were 24% (95% CI: 18% - 30%) and 10% (95% CI: 9% - 11%), respectively, and with a corresponding HR of 2.08 (95% CI: 1.49-2.91). Conclusion Among women with BC, prevalent T2D at the time of primary BC surgery increases the risk of postoperative complications. This excess risk is particularly pronounced among patients who undergo neoadjuvant chemotherapy. Citation Format: Kasper Kjærgaard, Jannik Wheler, Looket Dihge, Peer Christiansen, Signe Borgquist, Deirdre Cronin-Fenton. The Impact of Type 2 Diabetes on Complications after Primary Breast Cancer Surgery: a Danish population-based cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-10.