The joint effect of mental illness and parental suicide attempt on offspring suicide attempt and death: A Danish nationwide, registry-based study using multistate modeling.

AIM: The aim of this study was to analyse the joint impact of moderate-to-severe mental illness and parental suicidal attempts on suicidal attempt and premature death. METHODS: Using the Danish, nationwide health registries, a cohort study was conducted including the birth cohorts 1983-1989. Cox regression and multistate models were used to estimate relative and absolute risks of suicide attempt and premature death. OUTCOME: We included 384,569 individuals and 7,218 individuals experienced their first suicide attempt during follow-up, while 2,762 individuals died of all causes. Joined exposure to parental suicide attempt and own mental illness increased the relative risk of suicide attempt (HR 22.57) and premature death all causes (HR 3.17). The absolute risk of suicide attempt before the age of 35 years was 20 % for offspring exposed to both parental suicide attempts and own mental illness (23 % for women vs. 15 % for men), while the risk of death was 4 % (0.6 % for women vs. 7 % for men). CONCLUSION: Exposure to both parental suicide attempt and own mental illness increases the relative and absolute risks of suicide attempt and premature death with considerable differences across sex. These findings are important in the clinical assessment of individuals with suicidal behavior.

Comparative Analysis of Outpatient Antibiotic Prescribing in Early Life: A Population-Based Study Across Birth Cohorts in Denmark and Germany.

INTRODUCTION: Comparing antibiotic prescribing between countries can provide important insights into potential needs of improving antibiotic stewardship programs. We aimed to compare outpatient antibiotic prescribing in early life between children born in Denmark and Germany. METHODS: Using the Danish nationwide healthcare registries and a German claims database (GePaRD, ~ 20% population coverage), we included children born between 2004 and 2016, and followed them regarding outpatient antibiotic prescriptions until end of enrollment or the end of 2018. We then determined the median time to first antibiotic prescription. Based on all prescriptions in the first 2 years of life, we calculated the rate of antibiotic treatment episodes and for the children's first prescriptions in this period, we determined established quality indicators. All analyses were stratified by birth year and country. RESULTS: In the 2016 birth cohorts, the median time to first antibiotic prescription was ~ 21 months in Denmark and ~ 28 in Germany; the rate of antibiotic treatment episodes per 1000 person-years was 537 in Denmark and 433 in Germany; the percentage of prescribed antibiotics with higher concerns regarding side effects and/or resistance potential was 6.2% in Denmark and 44.2% in Germany. In the 2016 birth cohorts, the age at first antibiotic prescription was 50-59% higher compared to the 2004 birth cohorts; the rate of antibiotic treatment episodes was 43-44% lower. CONCLUSIONS: Infants in Denmark received antibiotics markedly earlier and more frequently than in Germany, while quality indicators of antibiotic prescribing were more favorable in Denmark. Although both countries experienced positive changes towards more rational antibiotic prescribing in early life, our findings suggest potential for further improvement. This particularly applies to prescribing antibiotics with a lower potential for side effects and/or resistance in Germany.

Use of molnupiravir: A Danish nationwide drug utilization study.

PURPOSE: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild-to-moderate COVID-19. METHODS: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs-CoV-2 test. Patient characteristics were compared to matched, untreated SARS-CoV-2 positive reference groups. RESULTS: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT-PCR SARS-CoV-2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT-PCR SARS-CoV-2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS-CoV-2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%). CONCLUSIONS: Molnupiravir was mainly prescribed by general practitioners to RT-PCR SARS-CoV-2 positive individuals who had a potentially increased risk of severe COVID-19. Though some off-label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Changing characteristics over time of individuals receiving COVID-19 vaccines in Denmark: A population-based descriptive study of vaccine uptake.

AIMS: The Danish authorities implemented a differential rollout of the COVID-19 vaccines where individuals at high risk of COVID-19 were prioritized. We describe the temporal uptake and characteristics of COVID-19 vaccine recipients in Denmark. METHODS: Using nationwide healthcare registries, we identified all Danish residents ⩾5 years of age who received at least one dose of a COVID-19 vaccine from 27 December 2020-29 January 2022. We charted the daily number of newly vaccinated individuals and the cumulative vaccine coverage over time, stratified by vaccine type, age groups and vaccination priority groups, and described characteristics of vaccine recipients during two-month-intervals and in vaccination priority groups. RESULTS: By 29 January 2022, 88%, 86% and 64% of Danish residents ⩾5 years (n=5,562,008) had received a first, second and third dose, respectively, of a COVID-19 vaccine, most commonly the BNT162b2 vaccine (84%). Uptake ranged from 48% in 5-11-year-olds to 98% in 65-74-year-olds. Individuals vaccinated before June 2021 were older (median age 61-70 years vs 10-35 years in later periods) and had more comorbidities such as hypertension (22-28% vs 0.77-2.8% in later periods), chronic lung disease (9.4-15% vs 3.7-4.6% in later periods) and diabetes (9.3-12% vs 0.91-2.4% in later periods). CONCLUSIONS: We document substantial changes over time in, for example, age, sex and medical history of COVID-19 vaccine recipients. Though these results are related to the differential vaccine rollout in Denmark, similar findings are probable in other countries and should be considered when designing and interpreting studies on the effectiveness and safety of COVID-19 vaccines.

Development and Validation of a Nordic Multimorbidity Index Based on Hospital Diagnoses and Filled Prescriptions.

Purpose: To develop the Nordic Multimorbidity Index (NMI), a multimorbidity measure specifically suited to the Nordic health and administrative registry data based on current diagnosis, treatment, and coding practices. Methods: The NMI was developed to predict 5-year mortality in a population-based cohort of randomly sampled Danish residents aged ≥40 years (n = 425,087) followed from 2013 to 2018. Included predictors were selected from hospital diagnoses and filled drug prescriptions based on a combination of subject matter knowledge and a data-driven approach using backwards elimination. The performance of the NMI was assessed in a temporal validation cohort of Danish residents followed from 2007 to 2012 and in six cohorts of new users of selected drugs. The discriminative performance of the NMI, Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) was assessed using the c-statistic from logistic regression models with 5-year mortality as dependent variable and the multimorbidity index score, age, and sex as independent variables. Results: The NMI included 50 predictors. In the temporal validation cohort, the c-statistic of the NMI (0.887, 95% CI 0.883-0.890) exceeded that of the CCI (0.871, 95% CI 0.868-0.874) and ECI (0.866, 95% CI 0.863-0.870). In all new user cohorts, the NMI outperformed the other indices with c-statistics ranging from 0.781 (95% CI 0.779-0.784) to 0.838 (95% CI 0.834-0.842). Conclusion: The NMI predicted 5-year mortality in a general Danish population and six cohorts of new users of selected drugs and was superior to the CCI and ECI. The NMI could be preferred over these indices to quantify the level of multimorbidity for, eg, descriptive purposes or confounding control. The NMI should be validated in other patient populations and other Nordic countries.

High-dose non-sedating antihistamines are used insufficiently in chronic urticaria patients treated with omalizumab.

BACKGROUND: The lifetime prevalence of chronic urticaria (CU) is 0.5%-1%. In some patients with CU, symptomatic control is not achieved with non-sedating second-generation H1 antihistamines (nsAH1) alone, even with quadrupled standard doses as recommended in international guidelines. In these cases, biological treatment with omalizumab can be added. Since omalizumab is expensive compared to antihistamines, lack of adherence to guidelines for high dose nsAH1 (up to four-fold standard dose per day) may be associated with substantial unnecessary costs. The aim was to measure the use nsAH1 before and during omalizumab use for the first time in an omalizumab treated CU population. METHODS: We identified all Danish patients with CU who initiated omalizumab from March 2014 to December 2018 and evaluated new and ongoing nsAH1 treatments using the Danish nationwide registries. RESULTS: A total of 955 CU patients initiated treatment with omalizumab within the study period (median age 40 years [IQR 28-50], 74.5% females). During the 12 months prior to omalizumab initiation, 95.6% of the patients filled at least one prescription with nsAH1 at some point, while 84.7% filled at least one prescription during the three months before omalizumab. From 3 months before omalizumab initiation till 3 months after, the proportions of users of high-dose nsAH1 was maximum 31.1%. CONCLUSIONS: Omalizumab was usually administered before sufficient nsAH1 treatment was tried. In despite of the labelling that omalizumab should be co-administered with high dose nsAH1, this does not happen This may lead to substantial unnecessary costs.

SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis.

OBJECTIVE: To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes. METHODS: This nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use. RESULTS: The study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users. CONCLUSIONS: ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic. TRIAL REGISTRATION NUMBER: EUPAS34887.

Renin-Angiotensin System Blockers and Adverse Outcomes of Influenza and Pneumonia: A Danish Cohort Study.

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.

Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.

BACKGROUND: Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI -3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI -3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI -3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI -2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD -0.2%, 95% CI -2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19. CONCLUSIONS: Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2. TRIAL REGISTRATION: The European Union electronic Register of Post-Authorisation Studies EUPAS34734.

Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: a nationwide cohort.

BACKGROUND: Population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) is urgently needed to inform targeted protection strategies in the general population. METHODS: We examined characteristics and predictors of hospitalization and death in a nationwide cohort of all Danish individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 27 February 2020 until 19 May 2020. RESULTS: We identified 11 122 SARS-CoV-2 polymerase chain reaction-positive cases of whom 80% were community-managed and 20% were hospitalized. Thirty-day all-cause mortality was 5.2%. Age was strongly associated with fatal disease {odds ratio [OR] 15 [95% confidence interval (CI): 9-26] for 70-79 years, increasing to OR 90 (95% CI: 50-162) for ≥90 years, when compared with cases aged 50-59 years and adjusted for sex and number of co-morbidities}. Similarly, the number of co-morbidities was associated with fatal disease [OR 5.2 (95% CI: 3.4-8.0), for cases with at least four co-morbidities vs no co-morbidities] and 79% of fatal cases had at least two co-morbidities. Most major chronic diseases were associated with hospitalization, with ORs ranging from 1.3-1.4 (e.g. stroke, ischaemic heart disease) to 2.6-3.4 (e.g. heart failure, hospital-diagnosed kidney disease, organ transplantation) and with mortality with ORs ranging from 1.1-1.3 (e.g. ischaemic heart disease, hypertension) to 2.5-3.2 (e.g. major psychiatric disorder, organ transplantation). In the absence of co-morbidities, mortality was <5% in persons aged ≤80 years. CONCLUSIONS: In this nationwide population-based COVID-19 study, increasing age and multimorbidity were strongly associated with hospitalization and death. In the absence of co-morbidities, the mortality was, however, <5% until the age of 80 years.

Existing Data Sources in Clinical Epidemiology: The Danish COVID-19 Cohort.

BACKGROUND: To facilitate research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a prospective cohort of all Danish residents tested for SARS-CoV-2 in Denmark is established. DATA STRUCTURE: All Danish residents tested by reverse transcriptase polymerase chain reactions (RT-PCR) for SARS-CoV-2 in Denmark are included. The cohort is identified using the Danish Microbiology Database. Individual-level record linkage between administrative and health-care registries is facilitated by the Danish Civil Registration System. Information on outcomes related to SARS-CoV-2 infection includes hospital admission, intensive care unit admission, mechanical ventilation, and death and is retrieved from the five administrative Danish regions, the Danish National Patient Registry, and the Danish Register of Causes of Death. The Patient Registry further provides a complete hospital contact history of somatic and psychiatric conditions and procedures. Data on all prescriptions filled at community pharmacies are available from the Danish National Prescription Registry. Health-care authorization status is obtained from the Danish Register of Healthcare Professionals. Finally, selected laboratory values are obtained from the Register of Laboratory Results for Research. The cohort is governed by a steering committee with representatives from the Danish Medicines Agency, Statens Serum Institut, the Danish Health Authority, the Danish Health Data Authority, Danish Patients, the Faculties of Health Sciences at the Danish universities, and Danish regions. The steering committee welcomes suggestions for research studies and collaborations. Research proposals will be prioritized based on timeliness and potential clinical and public health implications. All research protocols assessing specific hypotheses for medicines will be made publicly available using the European Union electronic Register of Post-Authorisation Studies. CONCLUSION: The Danish COVID-19 cohort includes all Danish residents with an RT-PCR test for SARS-CoV-2. Through individual-level linkage with existing Danish health and administrative registries, this is a valuable data source for epidemiological research on SARS-CoV-2.

Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza.

Importance: During the ongoing coronavirus disease 2019 pandemic, case reports have suggested that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes. Objective: To study the association of NSAID use with adverse outcomes in patients hospitalized with influenza or influenza pneumonia. Design, Setting, and Participants: This cohort study used propensity score matching among 7747 individuals aged 40 years or older who were hospitalized with influenza, confirmed by polymerase chain reaction or antigen testing, between 2010 and 2018. Data were collected using Danish nationwide registers. All analyses reported were performed on May 29, 2020. Exposures: Prescription fill of an NSAID within 60 days before admission. Main Outcomes and Measures: Risk ratio (RR) and risk difference (RD) with 95% CIs for intensive care unit admission and death within 30 days of admission. Results: A total of 7747 patients (median [interquartile range] age, 71 [59-80] years, 3980 [51.4%] men) with confirmed influenza were identified. Of these, 520 (6.7%) were exposed to NSAIDs. In the unmatched cohorts, 104 of 520 patients (20.0%) who used NSAIDs and 958 of 7227 patients (13.3%) who did not use NSAIDs were admitted to the intensive care unit. For death within 30 days of admission, we observed 37 events (7.1%) among those who used NSAIDs compared with 563 events (7.8%) among those who did not. Current NSAID use was associated with intensive care unit admission (RR, 1.51; 95% CI, 1.26 to 1.81; RD, 6.7%; 95% CI, 3.2% to 10.3%), while NSAID use was not associated with death (RR, 0.91; 95% CI, 0.66 to 1.26; RD, -0.7%; 95% CI, -3.0% to 1.6%). In the matched cohorts, risks were unchanged for patients who used NSAIDs, while 83 ICU admissions (16.0%) and 36 deaths (6.9%) were observed among matched individuals who did not use NSAIDs. Matched (ie, adjusted) analyses yielded attenuated risk estimates for intensive care unit admission (RR, 1.25; 95% CI, 0.95 to 1.63; RD, 4.0%; 95% CI, -0.6% to 8.7%) and death (RR, 1.03; 95% CI, 0.66 to 1.60; RD, 0.2%; 95% CI, -2.9% to 3.3%). Associations were more pronounced among patients who used NSAIDs for a longer period (eg, for intensive care unit admission: RR, 1.90; 95% CI, 1.19 to 3.06; RD, 13.4%; 95% CI, 4.0% to 22.8%). Conclusions and Relevance: In this cohort study of adult patients hospitalized with influenza, the use of NSAIDs was not associated with 30-day intensive care unit admission or death in adjusted analyses. There was an association between long-term use of NSAIDs and intensive care unit admission.

Use of medication among nursing home residents: a Danish drug utilisation study.

BACKGROUND: Data on drug utilisation patterns in nursing home populations is scarce. We aimed to describe drug use patterns in Danish nursing home residents. METHODS: We established a cohort of 5,179 individuals (63% women; median age of 84 years) admitted into 94 nursing homes across Denmark during 2015-2017. Data on prescription drug use and other census data were obtained from the nationwide Danish health registries. RESULTS: The total number of drug classes filled increased from a median of 6 drugs (interquartile range [IQR] 3-9) at 18-24 months before nursing home admission to a median of 8 drugs (IQR 6-11) just after admission, with the most common drug classes comprising paracetamol (61%), platelet inhibitors (41%), proton pump inhibitors (34%), statins (33%) and potassium supplements (31%). The incidence rate of new drug treatments increased from 21 new treatments/100 residents/month at 12-24 months before admission to a peak of 71 new treatments/100 residents/month in the month prior to admission, while it levelled off to about 34 new treatments/100 residents/month after 6-9 months. The drug classes primarily responsible for this peak were laxatives, antibiotics and analgesics. The largest absolute increases were seen for laxatives (53%), paracetamol (43%) and antidepressants (36%), all showing a marked increase up to and following admission. A high proportion of residents remained on therapy in the 3-year period following admission, with users of antidepressants and antidementia drugs being most persistent. CONCLUSION: Nursing home admission is associated with an increase in use of both predominantly preventive and non-preventive drug classes.

Long-term oral budesonide treatment and risk of osteoporotic fractures in patients with microscopic colitis.

BACKGROUND: Due to a substantial first-pass metabolism of oral budesonide, systemic bioavailability is low compared to other oral corticosteroids, thereby possibly avoiding adverse effects of systemic corticosteroid use. AIM: To determine whether use of oral budesonide is associated with osteoporotic fractures in patients with microscopic colitis (MC). METHODS: Applying data from the Danish nationwide health registries, we conducted a case-control study nested within a cohort of patients with MC from 2004 to 2012. We estimated odds ratios (ORs) for the association between budesonide use and osteoporotic fractures (hip, wrist and spinal fractures). RESULTS: We identified 417 cases with a first occurrence of an osteoporotic fracture. Eighty-six per cent were women and the median age was 78 years. The OR for the overall association between ever-use of budesonide and any osteoporotic fractures did not reach statistical significance (OR 1.13, CI: 0.88-1.47). The highest risk was observed for spinal fractures (OR 1.98, CI: 0.94-4.17), where a dose-response association seemed to exist, followed by hip and wrist fractures (OR 1.17 [CI: 0.79-1.73] and OR 0.99 [CI: 0.66-1.47] respectively). We generally found modestly increased ORs across subgroups at suspected high or low risk of fractures (1.00-2.49). No overall dose-response association was evident (OR for doubling of cumulative dose 0.93 (CI: 0.84-1.03). CONCLUSION: No overall association between use of oral budesonide and osteoporotic fractures was demonstrated among individuals with MC. There seemed to be an isolated adverse effect of budesonide on the risk of spinal fractures, which appears to be dose related.

Morbidity and mortality among older people admitted to nursing home.

BACKGROUND: the increasing number of multimorbid older people places high demands on future health care systems. To inform the discussion on how to structure future care strategies, we aimed to describe the temporal relationship between admission, and morbidity and mortality in nursing home residents. METHODS: data on 5,179 older individuals admitted to 94 Danish nursing homes in 12 municipalities during 2015-2017 were linked to the nationwide Danish health registries to retrieve information on the temporal relation between nursing home admission and morbidity and mortality. RESULTS: at the time of nursing home admission, the majority were women (63%). Male residents were younger than women (median 82 vs 85 years) and had a higher prevalence of comorbidities (median Charlson score 2 vs 1 among women). The median survival after nursing home admission was 25.8 months, with the 3-year survival being 37%. Three-year survival was lower among men (29 vs 43% among women) and among the oldest residents (23% among those aged ≥90 years vs 64% among individuals ≤65 years). In addition to age and sex, predictors of mortality included hospitalisations prior to nursing home admission and a high burden of comorbidity. The rate of hospitalisations, primarily for reasons related to frailty, increased substantially during the 9 months prior to nursing home admission. CONCLUSION: we provide detailed information on differences in morbidity and mortality across age span and sex at the time of nursing home admission, thereby contributing to the ongoing discussion of how to structure the future health care system.

Increased risk of major adverse cardiac events following the onset of acute exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Acute exacerbations in chronic obstructive pulmonary disease (COPD) may trigger major adverse cardiac events (MACE). We aimed to determine whether the risk of having MACE was transiently increased following the onset of an acute COPD exacerbation. METHODS: We conducted a nationwide, register-based study from 1997 to 2014 comprising individuals with an acute COPD exacerbation followed by a MACE (acute myocardial infarction (MI), stroke or cardiovascular death). Using the case-crossover design, we estimated odds ratios (OR) for the association between acute exacerbations of COPD and MACE as well as for single outcomes (acute MI, stroke and cardiovascular death), different levels of severity of exacerbations and within patient subgroups. RESULTS: We identified 118 807 cases with a MACE preceded by an exacerbation. Overall, the risk of MACE increased almost fourfold following the onset of an acute exacerbation compared to periods without exacerbations in the same individuals (OR: 3.70; 95% CI: 3.60-3.80). The associations were consistent for single outcomes (acute MI, OR: 3.57; cardiovascular death, OR: 4.33; and stroke, OR: 2.78) and particularly strong associations were demonstrated for severe exacerbations (OR: 5.92) and the oldest individuals (OR: 4.18). CONCLUSION: The risk of MACE increased substantially following the onset of an acute exacerbation. This highlights that prevention of cardiac events is an important goal in the management of COPD. Attention should be paid to detecting cardiovascular disease following acute COPD exacerbations.

Use of prescription drugs in the older adult population-a nationwide pharmacoepidemiological study.

PURPOSE: Multi-morbidity and polypharmacy are common among older people. It is essential to provide a better understanding of the complexity of prescription drug use among older adults to optimise rational pharmacotherapy. Population-based utilisation data in this age group is limited. Using the Danish nationwide health registries, we aimed to characterise drug use among Danish individuals ≥ 60 years. METHODS: This is a descriptive population-based study assessing drug prescription patterns in 2015 in the full Danish population aged ≥ 60 years. The use of specific therapeutic subgroups and chemical subgroups and its dependence on age were described using descriptive statistics. Profiles of drug combination patterns were evaluated using latent class analysis. RESULTS: We included 1,424,775 residents (median age 70 years, 53% women). Of all the older adults, 89% filled at least one prescription during 2015. The median number of drug groups used was five per person. The most used single drug groups were paracetamol and analogues (34%), statins (33%) and platelet aggregation inhibitors (24%). Eighteen drug profiles with different drug combination patterns were identified. One drug profile with expected use of zero drugs and 11 drug profiles expected to receive more than five different therapeutic subgroup drugs were identified. CONCLUSION: The use of drugs is extensive both at the population level and increasing with age at an individual level. Separating the population into different homogenous groups related to drug use resulted in 18 different drug profiles, of which 11 drug profiles received on average more than five different therapeutic subgroup drugs.

Discontinuation of therapy among COPD patients who experience an improvement in exacerbation status.

PURPOSE: A subset of patients with chronic obstructive pulmonary disease (COPD) experience a decrease in exacerbation frequency, leading to a diminished need for treatment with inhaled corticosteroids (ICS). We investigated prescribing and discontinuation patterns of long-acting bronchodilators and ICS in COPD patients according to exacerbation frequency. METHODS: Using the nationwide Danish health registries, we conducted a drug utilization study among patients who had at least two exacerbations or one hospitalization due to an exacerbation during 2011-2012. This study population was stratified according to consistency of exacerbation occurrence after 12, 24, 36, and 48 months of follow-up and the groups were described according to use of ICS, long-acting ß2-agonists (LABA), and long-acting anticholinergics (LAMA), and combinations thereof. RESULTS: We identified 29,010 COPD exacerbators during 2011-2012. Upon inclusion, 70% received ICS-containing regimens, in combination with LABA (23%) or both LABA and LAMA (41%). The proportion of prevalent users of ICS-containing regimens decreased to 56% during follow-up among exacerbation-free individuals, while it increased to 86% in individuals who experienced at least one exacerbation annually. Persistence to ICS-containing regimens was 58% after 4 years in individuals without exacerbations compared to 74% among those with annual exacerbations. Similar patterns were observed for triple therapy which was the most extensively used drug combination regardless of consistency of exacerbation occurrence. CONCLUSIONS: The extensive use of ICS and the relatively high persistence to ICS-containing regimens in individuals who had a decrease in exacerbation occurrence highlight a need for the development and implementation of de-escalation strategies in clinical practice.

Use of proton pump inhibitors among Danish children: A 16-year register-based nationwide study.

OBJECTIVES: Proton pump inhibitors (PPI) are among the most frequently used drugs in the developed countries. In recent years, their use among children and adolescents has been on the increase. Guidelines recommend use for a period no longer than 4-8 weeks. The aim of this study was to describe time trends in prescribing patterns of PPI use among children, with emphasis on persistence to therapy. METHODS: We used the Danish nationwide healthcare registries and identified all Danish children (0-17 years old) who were provided with a filled in PPI prescription between 2000 and 2015. Based on descriptive analyses, we reported trends over time in annual use, prevalent and incident users. Moreover, we evaluated persistence to treatment and doses used over time. Analyses were stratified by age groups (0-4, 5-11 and 12-17 years). RESULTS: We identified 212 056 filled in PPI prescriptions prescribed to 78 489 children. The total annual use of PPIs among children increased eight times from 2000 to 2015. Omeprazole was most frequently used (60% of all use). The proportion of prevalent users increased from 0.1 in 2000 to 3.1 per 1000 children in 2015, while the rate of new users increased from 1.2 to 8.0 per 1000 child years. In general, persistence to PPIs was low: in the youngest age groups (14%), slightly more children were covered by treatment 12 months after the first prescription compared with the oldest age groups (5%). CONCLUSION: The use of PPIs among Danish children has increased substantially during the last 15 years. In general, treatment with PPIs among children was of short duration. Attention should be paid to indications and rationality behind initiation of therapy.