Danish National Patient Registry Research Articles

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

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

BackgroundThe 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. MethodsUsing 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. ResultsAn 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). ConclusionsThe 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.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Outcome of Pediatric Large Vessel Occlusion Stroke in Denmark

BACKGROUND We performed a nationwide study to examine clinical outcome in children with large‐vessel occlusion (LVO) stroke treated with mechanical thrombectomy (MT) or conservatively. METHODS Study participants were enrolled by 2 methods: (1) registration of children assessed through a pediatric stroke triage‐setup from January 2021 to June 2023 and (2) identification of children registered with a stroke or stroke‐related diagnosis in the Danish National Registry of Patients between January 2011 and December 2020. Medical records were reviewed to validate possible stroke events. Children aged 29 days to 17 years with arterial ischemic stroke were included. The children were followed up for cause of stroke, site of vessel occlusion, treatment characteristics, and clinical outcome according to the modified Rankin scale. RESULTS A total of 181 children with arterial ischemic stroke were identified. Angiography descriptions were available in 133 children and demonstrated LVOs in 28 (21.1%) of these. Fourteen children with LVOs underwent MT and 14 were treated conservatively. Thirteen of 14 (92.9%) children treated with MT achieved successful reperfusion. Periprocedural complications were observed in 2 children, including 1 child who developed symptomatic intracerebral hemorrhage <24 hours from MT. Long‐term outcome was poor (modified Rankin scale score 3–6) in 7 out of 14 (50.0%) children with LVOs treated conservatively and 5 out of 14 (35.7%) children treated with MT. When limiting analysis to MT procedures performed within 24 hours from stroke onset, a poor outcome was observed in 3 out of 11 (27.3%) children treated with MT. Outcome did not differ significantly between treatment groups. CONCLUSION This nationwide study demonstrates that MT is feasible and apparently safe to use in children. Among children with LVOs, outcome tended to be better for those treated with MT than those treated conservatively, but outcome did not differ significantly between groups, likely due to small sample sizes.

Return to badminton play following an ACL injury is common, but only a few return to previous performance.

To report how many badminton players return to badminton after an anterior cruciate ligament (ACL) injury and to which level. Patients in Denmark from 2000 to 2018, registered in the Danish National Patient Register with a diagnosis of ACL rupture and badminton as a primary sport were asked about a return to sport (RTS) and return to performance (RTP) after ACL injury. RTP was defined as the return to full participation in the same sport, same level and same preinjury performance. To investigate the likelihood of RTS and return to preinjury level, a binominal logistic regression was used. Badminton was the primary sport for 900 participants. Only 435 players were injured during badminton, and 626 participants intended to RTP. RTS was achieved by 396 (63%)and 117 (19%) returned to the same performance as their preinjury level. However, 273 (44%) returned to full participation at the same level as the preinjury level but did not perform as well. Males had a significantly higher RTS than females, and RTP was also higher among males [221 (68%) vs. 175 (58%), odds ratio, OR: 1.67, p = 0.003 and 74 (23%) vs. 43 (14%), OR: 1.58, p = 0.05]. Return to badminton was achieved by 396 (63%), but only 117 (19%) returned to the same performance as their preinjury level after ACL injury. Females are less successful in RTS and RTP. Future research on improving RTS and the RTP rates in badminton, in general, and specifically for females is needed. Level II.

The Epidemiology of Hospital-Treated Alopecia Areata in Denmark, 1995-2016.

Alopecia areata (AA) is an autoimmune skin disease presenting as nonscarring hair loss. Information on the epidemiology of AA, especially the occurrence of AA and its subtypes within the general population, is scarce. The study aimed to estimate the incidence rates and prevalence of hospital-treated AA and its subtypes in Denmark and to examine the demographic and clinical characteristics of patients with AA, including comorbidities and use of prescription medications. This was a cohort study based on data from administrative and health registers in Denmark in 1995-2016. The study included individuals who were (1) registered with a hospital inpatient or hospital-based outpatient clinic diagnosis of AA between 1995 and 2016 in the Danish National Patient Registry covering encounters at all Danish hospitals, (2) alive and resided in Denmark anytime between 1995 and 2016, (3) aged ≥ 12years, and (4) resided uninterrupted in Denmark during the 12months before the first AA diagnosis during the study period. During the study period, 2778 individuals with an incident hospital-based diagnosis of AA were identified; 63.1% were female and 28.7% of the patients were aged ≥ 50years. Over the study period, the overall incidence rate for any hospital-treated AA per 100,000 person-years was 2.62 (95% confidence interval [CI], 2.53-2.72), and the overall prevalence in 2016 was 71.7 (95%CI 69.4-74.1) per 100,000 persons. Both incidence rate and prevalence increased over time. Prevalence of most hospital-treated comorbidities or history of medication use was below 10% and was similar in the alopecia totalis (AT)/alopecia universalis (AU) and non-AT/AU subtypes of AA. This cohort study reported incidence rates and prevalence over time and characteristics of individuals with hospital-treated AA in Denmark, which are in agreement with those previously reported in this population.

Amyotrophic Lateral Sclerosis Survival and Occupational Lead Exposure in the Danish National Patient Registry (P2-15.002)

Amyotrophic Lateral Sclerosis Survival and Occupational Lead Exposure in the Danish National Patient Registry (P2-15.002)

The asbestos-asbestosis exposure-response relationship: a cohort study of the general working population.

The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure-response relationship for asbestosis in a general working population setting. We examined the exposure-response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure-response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15- -1.22]. The IRR was 1.94 (95% CI 1.53-2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. This study found exposure-response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn'sdisease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD:IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. The clinical course of CD is milder for those who have previously undergone appendectomy.

Validity of Major Osteoporotic Fracture Diagnoses in the Danish National Patient Registry.

To evaluate the validity of diagnosis codes for Major Osteoporotic Fracture (MOF) in the Danish National Patient Registry (NPR) and secondly to evaluate whether the fracture was incident/acute using register-based definitions including date criteria and procedural codes. We identified a random sample of 2400 records with a diagnosis code for a MOF in the NPR with dates in the year of 2018. Diagnoses were coded with the 10th revision of the International Classification of Diseases (ICD-10). The sample included 2375 unique fracture patients from the Region of Southern Denmark. Medical records were retrieved for the study population and reviewed by an algorithmic search function and medical doctors to verify the MOF diagnoses. Register-based definitions of incident/acute MOF was evaluated in NPR data by applying date criteria and procedural codes. The PPV for MOF diagnoses overall was 0.99 (95% CI: 0.98;0.99) and PPV=0.99 for the four individual fracture sites, respectively. Further, analyses of incident/acute fractures applying date criteria, procedural codes and using patients' first contact in the NPR resulted in PPV=0.88 (95% CI: 0.84;0.91) for hip fractures, PPV=0.78 (95% CI: 0.74;0.83) for humerus fractures, PPV=0.78 (95% CI: 0.73;0.83) for clinical vertebral fractures and PPV=0.87 (95% CI: 0.83;0.90) for wrist fractures. ICD-10 coded MOF diagnoses are valid in the NPR. Furthermore, a set of register-based criteria can be applied to qualify if the MOF fracture was incident/acute. Thus, the NPR is a valuable and reliable data source for epidemiological research on osteoporotic fractures.

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

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. 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. 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. 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.

Risk of depression and anxiety in 7.302 patients with sarcoidosis: a nationwide cohort study.

The aim was to investigate the association between sarcoidosis and anxiety and/or depression (A/D) in patients with sarcoidosis and comparators matched on age, gender, residency, and cohabitation status. Patients with newly diagnosed sarcoidosis between 2001 and 2015 were identified in the Danish National Patient Register. Cases were matched 1:4 with non-sarcoidosis comparators. We estimated the cumulative incidence of A/D using the Cumulative Incidence Function and the subdistribution hazard ratio (sHR) for A/D using the Fine-Gray subdistribution hazard model. Estimates were adjusted for socio-economic status and Deyo-Charlson Comorbidity Index. We identified 7.302 cases and 26.145 matched comparators. The cumulative incidence of A/D after five years was 6.0% (95%CI 5.5-6.4) for cases and 4.2% (95%CI 4.0-4.4) for matched comparators. The cumulative incidence was higher among cases for both males and females and in all age-groups compared with the matched comparators. The adjusted-sHR for A/D was 1.38 (95%CI 1.24-1.53). The adjusted-sHR for A/D was 1.51 (95%CI 1.30-1.75) for male cases and 1.25 (95%CI 1.08-1.45) for female cases compared with the matched comparators. The adjusted-sHR for A/D was higher for cases in all age-groups compared with the matched comparators, although not statistically significant among cases aged 30-39 years (a-sHR 1.15; 95%CI 0.92-1.44). Sarcoidosis cases had a higher risk of A/D compared with matched comparators during 18 years of follow-up. The risk of developing A/D was greater for male and female cases and within all age-groups compared with the matched comparators.

Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study.

Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

Sleep disorders and sleep disturbances in persons with multiple sclerosis: A population-based matched case-control study in Denmark.

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

Congenital Tooth Agenesis and Risk of Early-Onset Cancer

There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting. To examine the association between tooth agenesis and specific cancer types before 40 years of age. This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 years. Data were analyzed from January through June 2023. Tooth agenesis as documented by the Danish Central Registry of Odontology (Danish municipal pediatric dental care) from January 1, 1988, to December 31, 2018, and from hospital encounters in the Danish National Patient Registry within the entire study period. The primary outcome was first cancer diagnosis before 40 years of age obtained from the Danish Cancer Registry. Associations between tooth agenesis and specific cancers were estimated by Cox proportional hazards regression as hazard ratios (HRs) with 95% CIs. Analyses were split into age groups: younger than 1 year, 1 to younger than 3 years, 3 to younger than 10 years, 10 to younger than 20 years, 20 to younger than 30 years, and 30 to younger than 40 years. Associations with nonsyndromic tooth agenesis were evaluated after exclusion of individuals with known syndromes. Among 2 501 715 included individuals (1 284 292 [51.3%] male), 70 288 (2.8%) had a diagnosis of tooth agenesis (mean [SD] age at diagnosis, 13.2 [4.1] years) and 26 308 (1.1%) had a diagnosis of early-onset cancer within the study period; 778 individuals had co-occurrence of tooth agenesis and cancer. Overall, tooth agenesis was positively associated with several cancer types, including neuroblastoma (age 1 to <3 years; HR, 4.20; 95% CI, 2.24-7.88), nephroblastoma (age 1 to <3 years; HR, 4.59; 95% CI, 2.37-8.91), hepatoblastoma (age 1 to <3 years; HR, 7.10; 95% CI, 2.70-18.68), osteosarcoma (age 10 to <20 years; HR, 2.19; 95% CI, 1.11-4.32), colorectal carcinomas (age 30 to <40 years; HR, 2.81; 95% CI, 1.38-5.71), and carcinomas of bladder (age 20 to <30 years; HR, 3.35; 95% CI, 1.35-8.30). This cohort study found associations between congenital tooth agenesis and several cancer types, from childhood to early adulthood. Further evaluation of these associations is needed to assess possible clinical implications.

Are Outcomes From an Exercise Therapy and Patient Education Program for Osteoarthritis Associated With Hip and Knee Replacement Within Two Years? A Register-Based Study of 9,339 Patients With Osteoarthritis.

The objective of this study was to determine whether short-term outcomes from exercise therapy and patient education for osteoarthritis (OA) are associated with hip or knee replacement within two years. Individual-level data from the Good Life with osteoArthritis in Denmark (GLA:D) Registry were linked to the Danish National Patient Registry and other national registries. Cox proportional hazards models were used to investigate associations between program outcomes (baseline to three-month changes) and time to primary hip or knee replacement. Patients who did not receive joint replacement were censored at two years, time of death, or emigration. A total of 2,304 and 7,035 patients with clinically diagnosed hip and knee OA, respectively, were included. Of these, 30% with hip OA and 10% with knee OA had joint replacement within two years. Postprogram improvements in hip-related quality of life and arthritis self-efficacy (pain subscale) were associated with a reduced hazard of hip replacement (adjusted hazard ratios [HRs] for a 10-unit improvement: 0.74 [95% confidence interval (CI) 0.69-0.80] and 0.90 [95% CI 0.85-0.96], respectively). Improvements in knee pain, knee-related quality of life, and arthritis self-efficacy (pain subscale) were associated with a lower hazard of knee replacement (adjusted HRs for 10-unit improvement: 0.81 [95% CI 0.76-0.86] to 0.90 [95% CI 0.86-0.95], 0.70 [95% CI 0.63-0.78] to 0.79 [95% CI 0.72-0.86], and 0.89 [95% CI 0.83-0.94], respectively). The magnitude of improvement in key measures after exercise therapy and education was significantly associated with the likelihood of surgery. Progression to hip replacement was three times higher than progression to knee replacement. This information can guide patient-clinician conversations around anticipated program outcomes.

Prevalence and Patient Characteristics of Ectodermal Dysplasias in Denmark

Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias. To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics. This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023. The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants. The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.

The Copenhagen Primary Care Laboratory (CopLab) Database.

The Copenhagen General Practice Laboratory (CGPL) was founded in 1922 to provide paraclinical analyses to the primary health-care sector in Copenhagen. At the end of 2015, CGPL was closed and the CopLab database was established to make CGPL data available for research. We isolated tests performed at the CGPL with clinically relevant test results. The database was linked to national registers containing health, social, and demographic information. Results are presented with descriptive statistics showing counts, percentages, medians, and interquartile ranges (IQR). The CopLab database includes 1,373,643 unique individuals from primary care with test results from laboratory analyses of blood/urine/semen as well as cardiac and lung function tests collected by CGPL from greater Copenhagen from 2000 to 2015. The CopLab database holds nearly all test results requested by general practitioners throughout years 2000 to 2015 for residents in the greater Copenhagen area. The median age of the individuals was 51 years and 59.7% were females. Each individual has a median of 4 requisitions. More than 1 million participants are currently alive and living in Denmark and may be followed in national registries such as the Danish National Patient Registry, Laboratory Database, National Prescription Database etc.

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark

ObjectivesAn increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke...

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

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