Association of postoperative opioid type with mortality and readmission rates: multicentre retrospective cohort study.

BACKGROUND: Opioid treatment in postoperative pain management is crucial, but the impact of administration practices on outcomes is unclear. The hypothesis was that prescription trends remained stable over recent years, and that no difference in mortality and readmission risks is associated with prescription strategies. METHOD: Electronic health records of surgical episodes in the Capital and Zealand Regions of Denmark from 2017 to 2021 were analysed. All opioids administered during postoperative admission were converted to oral morphine equivalents (OMEQs) and an average daily dose per patient was calculated. The opioid administered in the highest OMEQ dosages is considered the primary opioid strategy for the surgical case. Administration trends were analysed through linear regression, and Cox regression was used to calculate hazard ratios to assess dominant opioid strategies' association with 90-day mortality and readmission rates while controlling for confounders. RESULTS: A total of 183 317 patients met the inclusion criteria. Prescription trends remained steady during the study period. Multivariable analysis revealed increased readmission risk (HR 1.18, P < 0.001) of tramadol and tapentadol compared to morphine. They exhibited decreased 90-day mortality risk (HR 0.63, P < 0.001). Oxycodone had similar readmission risk (HR 1.009, P = 0.24) but lower 90-day mortality risk (HR 0.68, P < 0.001). CONCLUSION: Postoperative in-hospital opioid administration remained stable from 2017 to 2021. Tramadol/tapentadol had a higher risk of readmission but lower mortality risk. Oxycodone had comparable readmission but reduced mortality risk. This study provides a framework for future clinical trials assessing this potential impact of opioids in a targeted manner.

A register-based cohort study on the effectiveness and Safety of anti-PCSK9 treatment in persons with hyperlipidemia.

BACKGROUND: Dyslipidemia is a known risk factor for cardiovascular disease. While statins are the primary treatment, some individuals require additional lipid-lowering therapies, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Alirocumab and evolocumab have shown efficacy in reducing low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major cardiovascular events (MACE) but have not been directly compared in clinical trials. This study aims to assess the effects of PCSK9 inhibitors on LDL-C levels and evaluate the impact of a mandated switch from alirocumab to evolocumab. METHODS: Taking advantage of the mandated switch in PCSK9 treatment in Denmark, we conducted a register-based cohort study of 907 individuals with dyslipidemia treated with PCSK9 inhibitors in the Capital Region of Denmark from 2016 to 2022. We analyzed LDL-C levels, treatment retention, and MACE, adjusting for variables such as age, sex, dose, and concurrent lipid-lowering medications. RESULTS: We show that PCSK9 inhibitors treatment resulted in a 49% reduction in LDL-C levels. Following a mandated switch from alirocumab to evolocumab, no significant difference was observed in LDL-C levels or adverse clinical outcomes, including MACE. Treatment discontinuation was most likely within the first 100 days, and no significant difference in discontinuation rates was found between the two drugs. CONCLUSIONS: Our study demonstrates that both alirocumab and evolocumab are effective in significantly reducing LDL-C levels in individuals with dyslipidemia. The mandated switch from alirocumab to evolocumab did not result in significant changes in LDL-C or clinical outcomes, suggesting that these treatments can be used interchangeably. These findings support the clinical equivalence of the two PCSK9 inhibitors and may guide therapeutic decisions in lipid management.

Dyslipidemia is a condition where there are unhealthy levels of fats, i.e. cholesterol (LDL-C and HDL-C), in the blood, which can increase the risk of heart disease. To help manage this, certain drugs called PCSK9 inhibitors, like alirocumab and evolocumab, can be used to lower cholesterol levels. Here, we studied 907 people in Denmark who were treated with these drugs between 2016 and 2022. We found that these drugs reduced LDL-C by almost half. During the study, some people were required to switch from one drug (alirocumab) to another (evolocumab), and this switch did not lead to any changes in cholesterol levels or increase the risk of heart problems or death. Our findings suggest that both alirocumab and evolocumab are safe and effective options for lowering cholesterol, and they can be used interchangeably, which might help doctors make treatment decisions.

Rational Pharmacotherapy in Type 2 Diabetes: Danish Data From 2002 to 2020 on Mortality, Diabetes- Related Outcomes, Adverse Events, and Medication Expenses.

OBJECTIVE: Developments in pharmacotherapy and management of type 2 diabetes may have shifted the balance of treatment benefits versus harms and costs over the past decades. This study aimed to describe the trends in this balance. RESEARCH DESIGN AND METHODS: We followed the Danish population with type 2 diabetes between 2002 and 2020, analyzing their medication use in relation to treatment benefits (such as mortality and diabetes-related outcomes), adverse events, and medication costs. Using multivariate analyses, we adjusted for potential confounders, including age, sex, and socioeconomic status. RESULTS: The study included 461,805 individuals. From 2002 to 2020, the median age increased from 66 to 68 years, and the mean number of comorbidities increased from 5.2 to 8.8. The overall incidence of cardiovascular, renal, and other important adverse clinical outcomes decreased. Similarly, the rate of some adverse events, such as gastric bleeding, hypoglycemia, and falls declined, whereas the incidence of electrolyte imbalances and ketoacidosis increased. The average per-patient cost was reduced by 8%, but total medication expenses increased by 148% due to an expanding population size, lowered costs of most cardiovascular medications, and increasing costs for glucose-lowering drugs. CONCLUSIONS: Advancements in type 2 diabetes management have led to reduced risk of both diabetes-related outcomes and treatment harms, while maintaining relatively stable per-patient medication expenses. Although these trends are multifactorial, they suggest more rational pharmacotherapy. Still, increased risk of certain adverse events, along with increasing costs for glucose-lowering medications, underscores the need for ongoing vigilance and risk-benefit analysis.

COVID-19-associated cerebral microbleeds in the general population.

Cerebral microbleeds are frequent incidental findings on brain MRI and have previously been shown to occur in Coronavirus Disease 2019 (COVID-19) cohorts of critically ill patients. We aimed to determine the risk of having microbleeds on medically indicated brain MRI and compare non-hospitalized COVID-19-infected patients with non-infected controls. In this retrospective case-control study, we included patients over 18 years of age, having an MRI with a susceptibility-weighted sequence, between 1 January 2019 and 1 July 2021. Cases were identified based on a positive reverse transcriptase polymerase chain reaction test for SARS-CoV-2 and matched with three non-exposed controls, based on age, sex, body mass index and comorbidities. The number of cerebral microbleeds on each scan was determined using artificial intelligence. We included 73 cases and 219 matched non-exposed controls. COVID-19 was associated with significantly greater odds of having cerebral microbleeds on MRI [odds ratio 2.66 (1.23-5.76, 95% confidence interval)], increasingly so when patients with dementia and hospitalized patients were excluded. Our findings indicate that cerebral microbleeds may be associated with COVID-19 infections. This finding may add to the pathophysiological considerations of cerebral microbleeds and help explain cases of incidental cerebral microbleeds in patients with previous COVID-19.

Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system.

Introduction: Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments. Methods: An observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis. Results: Spontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA. Conclusion: Overall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed.

Increasing Medication Use and Polypharmacy in Type 2 Diabetes: The Danish Experience From 2000 to 2020.

OBJECTIVE: Type 2 diabetes often coexists with other conditions that are amenable to pharmacological treatment. We hypothesized that polypharmacy among individuals with type 2 diabetes has increased since 2000. RESEARCH DESIGN AND METHODS: Using Danish national registries, we established a cohort of all Danish individuals (aged ≥18 years) with type 2 diabetes between 2000 and 2020. We analyzed their medication use and prevalence of varying degrees of polypharmacy (≥5 or ≥10 medications), stratifying by age, sex, number of chronic diseases, and socioeconomic status. RESULTS: The cohort grew from 84,917 patients in 2000 to 307,011 in 2020, totaling 461,849 unique patients. The number of daily medications used per patient increased from (mean ± SD) 3.7 ± 2.8 (in 2000) to 5.3 ± 3.2 (in 2020). The lifetime risk of polypharmacy was substantial, with 89% (n = 409,062 of 461,849) being exposed to ≥5 medications at some point and 47% (n = 217,467of 461,849) to ≥10 medications. The increases were driven by an expanding group of medications, with analgesics, antihypertensives, proton pump inhibitors, and statins having the largest net increase. Advanced age, male sex, lower socioeconomic status, and Danish ethnicity positively correlated with polypharmacy but could not explain the overall increase in polypharmacy. CONCLUSIONS: Medication use and polypharmacy have increased among patients with type 2 diabetes. Although the implications and appropriateness of this increased medication use are uncertain, the results stress the increasing need for health care personnel to understand the potential risks associated with polypharmacy, including medication interactions, adverse effects, and over- and underprescribing.

Identifying people living with cystic fibrosis in the Danish National Patient Registry: A validation study.

BACKGROUND: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. METHODS: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. RESULTS: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). CONCLUSIONS: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Importance: Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. Objective: To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. Design, Setting, and Participants: This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Exposures: Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Main Outcomes and Measures: Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Results: Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. Conclusions and Relevance: The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

Temporal trends and regional variability in BRAF and KRAS genetic testing in Denmark (2010-2022): Implications for precision medicine.

OBJECTIVE: This study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022. STUDY DESIGN AND SETTING: Using comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions. RESULTS: The study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed. CONCLUSION: Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.

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

PURPOSE: Metronidazole, 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. METHODS: We 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. FINDINGS: Out 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. IMPLICATIONS: Our 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.

Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020.

BACKGROUND AND AIMS: Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. METHODS: Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. RESULTS: A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. CONCLUSIONS: Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

The impact of type 2 diabetes and glycaemic control on mortality and clinical outcomes in hospitalized patients with COVID-19 in the capital region of Denmark.

AIM: To explore the impact of type 2 diabetes (T2D), glycaemic control and use of glucose-lowering medication on clinical outcomes in hospitalized patients with COVID-19. MATERIALS AND METHODS: For all patients admitted to a hospital in the Capital Region of Denmark (1 March 2020 to 1 December 2021) with confirmed COVID-19, we extracted data on mortality, admission to intensive care unit (ICU), demographics, comorbidities, medication use and laboratory tests from the electronic health record system. We compared patients with T2D to patients without diabetes using Cox proportional hazards models adjusted for available confounding variables. Outcomes were 30-day mortality and admission to an ICU. For patients with T2D, we also analysed the association of baseline haemoglobin A1c (HbA1c) levels and use of specific glucose-lowering medications with the outcomes. RESULTS: In total, 4430 patients were analysed, 1236 with T2D and 2194 without diabetes. The overall 30-day mortality was 19% (n = 850) and 10% (n = 421) were admitted to an ICU. Crude analyses showed that patients with T2D both had increased mortality [hazard ratio (HR) 1.37; 95% CI 1.19-1.58] and increased risk of ICU admission (HR 1.28; 95% CI 1.04-1.57). When adjusted for available confounders, this discrepancy was attenuated for both mortality (adjusted HR 1.13; 95% CI 0.95-1.33) and risk of ICU admission (adjusted HR 1.01; 95% CI 0.79-1.29). Neither baseline haemoglobin A1c nor specific glucose-lowering medication use were significantly associated with the outcomes. CONCLUSION: Among those hospitalized for COVID-19, patients with T2D did not have a higher risk of death and ICU admission, when adjusting for confounders.

Age disparities in glucose-lowering treatment for Danish people with type 2 diabetes: a cross-sectional study between 2019 and 2020.

BACKGROUND: The pharmacotherapeutic guidelines for type 2 diabetes have changed considerably during the past decades. SGLT2 inhibitors and GLP-1 receptor agonists have emerged as first-line agents by preventing cardiovascular events within a few years of treatment. In contrast, sulphonylureas and insulin have been deprioritised due to less beneficial effects and the risk of hypoglycaemia-particularly in older people who are frail. We hypothesised that medications with a high risk of hypoglycaemia were used more often in older people compared with younger people. METHODS: In a nationwide cohort of people with type 2 diabetes in Denmark from 2019 to 2020, we described the use of specific glucose-lowering medications in relation to age and glycated haemoglobin A1C (HbA1c) by descriptive statistics and regression models adjusted for sex, socioeconomic factors, renal function, and several comorbidities. FINDINGS: Among 290 890 people with type 2 diabetes, glucose-lowering medication usage peaked at age 70 years. Increasing age was associated with relatively less use of metformin, GLP-1 receptor agonists, and SGLT2 inhibitors and more use of basal insulin, DDP-4 inhibitors, and sulphonylureas. When comparing 80-year-olds with 60-year-olds at similar HbA1c levels of 6·5% (48 mmol/mol), 80-year-olds used 8% (95% CI 7-10%) fewer glucose-lowering medications, were 55% less likely to receive GLP-1 receptor agonists or SGLT2 inhibitors (relative ratio 0·45, 95% CI 0·42-0·48), and 65% more likely to receive sulphonylureas (1·65, 1·54-1·76). Among 23 032 individuals aged 80 years or older with HbA1c levels of less than 6·5% (<48 mmol/mol), 2291 (10%) used sulphonylureas or insulin. INTERPRETATION: In Danish people with type 2 diabetes, the likelihood of using glucose-lowering medications with a high risk of hypoglycaemia (eg, sulphonylureas and basal insulin) increased with age, whereas the likelihood of using GLP-1 receptor agonists and SGLT2 inhibitors decreased. Some people aged 80 years or older with an HbA1c level of less than 6·5% (48 mmol/mol) were potentially overtreated with sulphonylureas or insulin. These findings emphasise the importance of frequently re-evaluating glucose-lowering treatments. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.

KRAS G12C mutated advanced non-small cell lung cancer (NSCLC): Characteristics, treatment patterns and overall survival from a Danish nationwide observational register study.

OBJECTIVES: We aimed to characterize the advanced NSCLC population in terms of KRAS G12C prevalence, patient characteristics, and survival outcomes after the introduction of immunotherapies. MATERIALS AND METHODS: We identified adult patients diagnosed with advanced NSCLC between January 1, 2018 and June 30, 2021 using the Danish health registries. Patients were grouped by mutational status (any KRAS mutation, KRAS G12C, and KRAS/EGFR/ALK wildtype [Triple WT]). We analyzed KRAS G12C prevalence, patient and tumor characteristics, treatment history, time-to-next-treatment (TTNT), and overall survival (OS). RESULTS: We identified 7,440 patients of whom 40% (n = 2,969) were KRAS tested prior to the first line of therapy (LOT1). Among the KRAS tested, 11% (n = 328) harbored KRAS G12C. More KRAS G12C patients were women (67%), smokers (86%), had a high (≥50%) level of PD-L1 expression (54%), and more frequently received anti-PD-L1 treatment than any other group. From the date of the mutational test result, OS (7.1-7.3 months) was similar between the groups. OS from LOT1 (14.0 months) and LOT2 (10.8 months), and TTNT from LOT1 (6.9 months) and LOT2 (6.3 months) was numerically longer for the KRAS G12C mutated group compared to any other group. However, from LOT1 and LOT2, the OS and TTNT were comparable when stratifying the groups by PD-L1 expression level. Regardless of the mutational group, OS was markedly longer for patients with high PD-L1 expression. CONCLUSION: In patients diagnosed with advanced NSCLC after the implementation of anti-PD-1/L1 therapies, the survival in KRAS G12C mutated patients is comparable to patients with any KRAS mutation, Triple WT, and all NSCLC patients.

Discontinuation of antipsychotics in individuals with first-episode schizophrenia and its association to functional outcomes, hospitalization and death: a register-based nationwide follow-up study.

BACKGROUND: Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death. METHODS: Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995-2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2-5. Outcomes year 5-6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression. RESULTS: Among 21 351, 9.3% took antipsychotics continuously year 2-5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53-2.56 and OR 2.60, 95% CI 1.91-3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05-1.48 and 2.04, 95% CI 1.64-2.53) and no antipsychotics (OR 2.00, 95% CI 1.69-2.38 and 5.64, 95% CI 4.56-6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10-1.47) and longer admissions (IRR 1.68, 95% CI 1.30-2.16) year 5-6 compared to continuous users. Mortality during year 5-6 did not differ between groups. CONCLUSION: Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.

Duloxetine Exposure During Pregnancy and the Risk of Offspring Being Born Small for Gestational Age or Prematurely: A Nationwide Danish and Swedish Safety Study.

BACKGROUND: Depression or depressive symptoms are common among pregnant women. The use of antidepressants during pregnancy has grown steadily. The risk of offspring being born small for gestational age or prematurely when exposed to duloxetine during pregnancy is not established. OBJECTIVE: We aimed to investigate the association between duloxetine exposure during pregnancy and offspring being born small for gestational age or prematurely. METHODS: We conducted an observational study including live births in Sweden and Denmark (2004-2016). Duloxetine exposure during early (0-140 days) or late (141 to delivery) pregnancy compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, venlafaxine-exposed, and duloxetine discontinuers. RESULTS: In total, 2,083,467 pregnancies were identified, where 1589 and 450 were duloxetine exposed in early and late pregnancy, respectively. For small for gestational age, no increased risk was seen for duloxetine across comparators. In the early and late exposure windows, propensity score-matched odds ratios for small for gestational age ranged between 0.64 (95% confidence interval 0.44-0.95) and 1.48 (95% confidence interval 0.85-2.57). For preterm birth, the findings differed across comparators and exposure-time windows, but trended towards an increased risk for duloxetine-exposed when compared with duloxetine-non-exposed, selective serotonin reuptake inhibitor-exposed, and duloxetine discontinuers in both early exposure and late exposure. The odds ratios ranged between 1.17 and 2.04, of which some did not reach statistical significance. No clear association was observed when compared with venlafaxine exposed, 0.91 (95% confidence interval 0.73-1.14) for early exposure and 1.26 (95% confidence interval 0.86-1.86) for late exposure. Most preterm births (79.2%) occurred in weeks 33-36 of gestation. CONCLUSIONS: Duloxetine exposure during pregnancy is unlikely to increase the risk of small for gestational age. Although not consequently statistically significant across comparisons, a trend towards an increased risk of preterm birth was observed for duloxetine exposed. Therefore, an increased risk of preterm birth cannot be excluded, especially for women exposed to duloxetine throughout pregnancy.

Healthcare resource utilization in patients with treatment-resistant depression-A Danish national registry study.

OBJECTIVES: To investigate healthcare resource utilization (HRU) and associated costs by depression severity and year of diagnosis among patients with treatment-resistant depression (TRD) in Denmark. METHODS: Including all adult patients with a first-time hospital contact for major depressive disorder (MDD) in 1996-2015, TRD patients were defined at the second shift in depression treatment (antidepressant medicine or electroconvulsive therapy) and matched 1:2 with non-TRD patients. The risk of utilization and amount of HRU and associated costs including medicine expenses 12 months after the TRD-defining date were reported, comparing TRD patients with non-TRD MDD patients. RESULTS: Identifying 25,321 TRD-patients matched with 50,638 non-TRD patients, the risk of psychiatric hospitalization following TRD diagnosis was 138.4% (95%-confidence interval: 128.3-149.0) higher for TRD patients than for non-TRD MDD patients. The number of hospital bed days and emergency department (ED) visits were also higher among TRD patients, with no significant difference for somatic HRU. Among patients who incurred healthcare costs, the associated HRU costs for TRD patients were 101.9% (97.5-106.4) higher overall, and 55.2% (50.9-59.6) higher for psychiatric services than those of non-TRD patients. The relative differences in costs for TRD-patients vs non-TRD patients were greater for patients with mild depression and tended to increase over the study period (1996-2015), particularly for acute hospitalizations and ED visits. LIMITATIONS: TRD was defined by prescription patterns besides ECT treatments. CONCLUSION: TRD was associated with increased psychiatric-related HRU. Particularly the difference in acute hospitalizations and ED visits between TRD and non-TRD patients increased over the study period.