Danish Cohort Research Articles

Short-term and long-term stroke risk following SARS-CoV-2 infection in relation to disease severity: a Danish national cohort study

ObjectivesStudies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke...

Psychosocial and mental impact of alopecia areata: Analysis of the Danish Skin Cohort

AbstractImportanceAlopecia areata (AA) carries a psychological burden for patients beyond hair loss. However, quality‐of‐life measurement tools such as EQ‐5D used in clinical trials may not adequately capture the burden of AA, the perceived stigmatization or the psychosocial impact of AA.ObjectiveTo investigate the potential association between disease severity and the degree of social isolation, perceived stigmatization, anxiety and depression, alcohol consumption and work absenteeism using multiple PRO measures in patients with AA.Design, Setting and ParticipantsUsing the Danish Skin Cohort, the study included adult patients diagnosed with AA. The study included multiple PRO measures, including Skindex‐16, EQ‐5D‐5L, Work Productivity and Activity Impairment (WPAI), Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) and the Alopecia Areata Symptom Impact Scale (AASIS). The questionnaires were dispatched to the patients in January 2023. The severity of AA was determined based on scalp involvement using a modified Alopecia Areata Scale. Multiple multivariate linear regressions were conducted using Skindex‐16, AASIS and WPAI, while multivariate logistic regressions were applied to HADS, AUDIT‐C and EQ‐5D‐5L.ResultsA total of 376 patients were included, of which 177 (47%) had severe disease, 41 (11%) had moderate disease, 94 (25%) had mild disease, and 64 (17%) were in remission. The median age of patients was 55 (IQR, 47–66 years) and most were female (70%). Skindex‐16 and AASIS were the only PRO measures able to distinguish between severity. For these scores, moderate and severe diseases, female sex, and involvement of eyebrows increased the score and negatively impacted patient quality of life.Conclusion and RelevanceThe results indicate the importance of using the proper tool for the intended measurement of quality of life and that factors such as the severity of AA, as well as female sex and involvement of the eyebrows, may potentially increase the psychosocial burden of AA.

Cervical cancer screening integrated in routine clinical care of women with HIV.

To evaluate if integrated cervical cancer screening (CCS) for women with HIV (WWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of human papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities. Cohort study. WWH who accepted the offer of combined CCS and HIV care (group 1), WWH who declined the offer (group 2), and WWH not offered CCS within HIV care (group 3) between 2013 and 2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WWH were screened annually. A total of 804 WWH were included. WWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22-99% compared with the WWH who declined CCS (group 2; n = 232) 10-16% and WWH who were not invited for CCS (group 3; n = 354) 11-25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups. Integrating CCS for WWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WWH in HIV care into preventive services.

Examining the influence of Covid-19 restrictions, a nurse strike, and SARS-CoV-2 coinfection on bacteremia mortality: A Danish population-based cohort study (2019–2022)

ObjectivesBacteremia is an acute severe infection with high mortality. Changes in healthcare services and coinfections with SARS-CoV-2 may have affected the mortality for bacteremia during the COVID-19 pandemic, which has been reported for other major diseases. In this study we examine the all-cause bacteremia mortality amidst the COVID-19 pandemic. MethodsA population-based cohort study comprised of laboratory confirmed bacteremia episodes in the Capital Region, Denmark (March 2019–February 2022). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI) for all-cause bacteremia mortality associated with the Covid-19 restriction period, a strike period, and coinfection with SARS-CoV-2, adjusted for possible confounders. ResultsA total of 14,912 bacteremia episodes were identified in 12,693 patients during the study period. The 30- and 90-day all-cause mortality were 19 % and 27 %, respectively. The fully adjusted HR for 30- and 90-day all-cause mortality associated with the Covid-19 restriction period were 0.91 (95 % CI, 0.84 to 0.99) and 0.90 (95 % CI, 0.84 to 0.96), respectively, compared to the remaining time period. The corresponding HRs associated with SARS-CoV-2 coinfection were 1.29 (95 % CI, 1.11 to 1.50) and 1.36 (95 % CI, 1.20 to 1.55) compared to patients without coinfection. The association between the national nurse strike and all-cause bacteremia mortality was inconclusive. ConclusionsIn this large population-based cohort study, a significant reduction in all-cause mortality for bacteremia was observed during the Covid-19 restriction period in Denmark, while coinfection with SARS-CoV-2 seem to be a substantial risk factor for all-cause bacteremia mortality.

Urticaria and the risk of cancer: a Danish population-based cohort study.

Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We conducted a population-based cohort study using healthcare databases covering the Danish population (January 1980-December 2022). We followed 87 507 people for a median of 10.1 years after their first hospital contact for urticaria. To examine associations of a hospital diagnosis of urticaria with incident cancer. We computed the absolute risk of cancer and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) standardized to Danish national cancer rates. In a cross-sectional analysis, we examined whether the extent of cancer spread differed between people with vs. without a previous urticaria diagnosis. The overall SIR for all types of cancer was 1.09 (95% CI 1.06-1.11) based on 7788 observed vs. 7161 expected cases. The risk for any cancer was 0.7% (95% CI 0.6-0.7) for the first year of follow-up. Cancer was diagnosed in 588 people with urticaria during the first year of follow-up (SIR 1.49, 95% CI 1.38-1.62) and in 7200 people thereafter (SIR 1.06, 95% CI 1.04-1.09). During the first year of follow-up, we found strong associations with haematological cancers (e.g. non-Hodgkin lymphoma; SIR 2.91, 95% CI 1.92-4.23). Cancer stage was similar in people with vs. without a previous urticaria diagnosis. At the time of urticaria diagnosis, or in the first year afterward, we found a large increase in the risk of cancer. In subsequent years, a persistent 6% increase in risk remained. Diagnostic efforts may partly explain the elevated short-term risk, but occult cancer may promote urticaria, or cancer and urticaria share common risk factors.

Text message questionnaires for Patient-Reported Outcome Measures after Cesarean section-A feasibility study.

Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)-based questionnaires may offer a low-cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS-based questionnaires. Prospective Danish single-center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS-based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30. Response rate and time from receiving the SMS to completion of the questionnaires. Opioid consumption and Patient Reported Outcomes Measures on pain and recovery. From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS-based questionnaire at 6 h after cesarean section was 23 min (IQR 2-72), decreasing to 20 min (IQR 2-78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65-84) at 6 h, decreasing to 28% (95% CI 34-58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20-50). SMS-based questionnaires on Patient Reported Outcome Measures are a feasible and cost-effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain-management within this timeframe.

Risk and Prognosis of Cancer in Patients with Obstructive Uropathy Compared with the General Danish Population.

To examine whether obstructive uropathy is associated with increased risk of cancer and whether mortality differs between patients with cancer with and without obstructive uropathy. In a nationwide population-based Danish cohort study including 37,275 adult patients with a first-time hospital-related diagnosis of obstructive uropathy in 1996 to 2022, we assessed cumulative cancer incidence (risk) and standardized incidence ratios (SIR). Furthermore, we compared the mortality of 7,485 patients diagnosed with cancer after obstructive uropathy diagnosis with that of 69,785 patients with cancer without obstructive uropathy matched by age, sex, cancer site, stage, and calendar year of cancer diagnosis. The 3-month risk of cancer after an obstructive uropathy diagnosis was 9.6%. The 3-month SIR was 34.2 [95% confidence interval (CI), 33.1-35.4] while the 1 to <5 year SIR was 1.2 (95% CI, 1.1-1.3). The 3-month SIRs were 82.7 (95% CI, 79.3-86.2) for urological cancer, 88.8 (95% CI, 79.8-98.5) for gynecological cancer, and 13.9 (95% CI, 12.0-15.9) for colorectal cancer. After 1 year of follow-up, the excess number of urological cancers decreased to 0.1 per 100 person-years, whereas we observed no excess risk of gynecological and colorectal cancers. The 5-year all-cause mortality following cancer was 64.1% (95% CI, 62.9-65.2) in patients with an obstructive uropathy diagnosis before cancer diagnosis and 53.2% (95% CI, 52.9-53.6) in those without. A first-time diagnosis of obstructive uropathy can be a clinical marker of underlying undiagnosed cancer and elevated mortality in relation to any cancer diagnosed after obstructive uropathy. These findings can inform the follow-up recommendations for obstructive uropathy.

Housing conditions and risk of incident COPD: a Danish cohort study, 2000–2018

BackgroundMore knowledge is needed on the risk of developing chronic obstructive pulmonary disease (COPD) associated with housing conditions and indoor environment based on cohort studies with a long follow-up time.ObjectiveTo examine the association between housing conditions and indoor environment and the risk of developing COPD.MethodsIn this cohort study, we followed 11,590 individuals aged ≥ 30 years free of COPD at baseline. Information on incident COPD and housing conditions and indoor environment was obtained from the Danish national registers and the Danish Health and Morbidity Survey year 2000. Poisson regression of incidence rates (IRs) were used to estimate incidence rate ratios (IRRs) of COPD.ResultsThe overall IR of COPD was 8.6 per 1,000 person-years. Individuals living outside the biggest cities vs. living in the biggest cities (≥ 50,000) had a lower risk of COPD (200-4,999; IRR 0.77 (95% CI 0.65-0.90). Individuals living in semi-detached houses had a higher risk compared to individuals living in detached houses (IRR 1.29 (95% CI 1.07-1.55)). Likewise, individuals living in rented homes had a higher risk (IRR 1.47 (95% CI 1.27-1.70)) compared to individuals living in owned homes. The IR of COPD was 17% higher among individuals living in dwellings build > 1982 compared with individuals living in older dwellings (< 1962), not statistically significant though (IRR 0.83 (95% CI 0.68-1.03)). Likewise, the IR of COPD was 15% higher among individuals living in the densest households compared with individuals living in the least dense households, not statistically significant though (IRR 1.15 (95% CI 0.92-1.45)). This was primary seen among smokers. There was no difference in risk among individuals with different perceived indoor environments. Overall, similar patterns were seen when stratified by smoking status with exception of perceived indoor environment, where opposite patterns were seen for smokers and never smokers.ConclusionIndividuals living in semi-detached houses or rented homes had a higher risk of developing COPD compared to individuals living in detached or owned homes. Individuals living in cities with < 50.000 residents had a lower risk of COPD compared to individuals living in cities with ≥ 50.000 residents.

Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health

The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10–8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10–9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10–8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.

Cost analysis of open versus robot-assisted ventral hernia repair – a retrospective cohort study

BackgroundRobot-assisted ventral hernia repair is associated with decreased length of stay and lower complication rates compared with open repair, but acquisition and maintenance of the robotic system is costly. The aim of this was study was to compare the procedure-specific cost of robot-assisted and open ventral and incisional hernia repair including cost of procedure-related readmissions and reoperations within 90 days postoperatively.MethodsSingle-center retrospective cohort study of 100 patients undergoing robot-assisted ventral hernia. Patients were propensity-score matched 1:1 with 100 patients undergoing open repairs on age, type of hernia (primary/incisional), and horizontal defect size. The primary outcome of the study was the total cost per procedure in Euros including the cost of a robotic approach, extra ports, mesh, tackers, length of stay, length of readmission, and operative reintervention. The cost of the robot itself was not included in the cost calculation.ResultsThe mean length of stay was 0.3 days for patients undergoing robot-assisted ventral hernia repair, which was significantly shorter compared with 2.1 days for patients undergoing open repair, P < 0.005. The readmission rate was 4% for patients undergoing robot-assisted ventral hernia repairs and was significantly lower compared with open repairs (17%), P = 0.006. The mean total cost of all robot-assisted ventral and incisional hernia repairs was 1,094 euro compared with 1,483 euro for open repairs, P = 0.123. The total cost of a robot-assisted incisional hernia repair was significantly lower (1,134 euros) compared with open ventral hernia repair (2,169 euros), P = 0.005.ConclusionsIn a Danish cohort of patients with incisional hernia, robot-assisted incisional hernia repair was more cost-effective than an open repair due to shortened length of stay, and lower rates of readmission and reintervention within 90 days.

Risk of fractures following bariatric surgery with Roux-en-Y gastric bypass or sleeve gastrectomy: a Danish population-based cohort study.

We examined the association between Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and fracture risk, including major osteoporotic fractures (MOF), and the use of anti-osteoporosis medication (AOM). While RYGB is associated with impaired bone health and increased fracture risk, it remains uncertain whether SG has a similar impact and whether this risk is primarily due to MOF or any fracture. We conducted a nationwide cohort study covering patients treated with RYGB (n = 16 121, 10.2-year follow-up) or SG (n = 1509, 3.7-year follow-up), from 2006 to 2018, comparing them with an age- and sex-matched cohort (n = 407 580). We computed incidence rates and adjusted hazard ratios (HRs) with 95% CIs, using Cox regression for any fracture, MOF, and use of AOM with adjustment for comorbidities. Compared with the general population cohort, RYGB was associated with an increased risk of any fracture (HR 1.56 [95% CI, 1.48-1.64]) and MOF (HR 1.49 [1.35-1.64]). Sleeve gastrectomy was associated with an increased risk of any fracture (HR 1.38 [1.13-1.68]), while the HR of MOF was 1.43 (0.97-2.12). The use of AOM was low but similar in all cohorts (approximately 1%). Bariatric surgery increased the risk of any fracture and MOF to similar extend. Risks were similar for RYGB and SG. However, SG had a shorter follow-up than RYGB, and the cohort size was rather small. More research is needed for long-term SG fracture risk assessment. The use of AOM was low in all cohorts.

Socioeconomic status and risk of cardiovascular diseases in patients with retinal vein occlusion: A Danish nationwide cohort study

PurposeThis study examines the association between socioeconomic status and the occurrence of both cardiovascular diseases and mortality following retinal vein occlusion (RVO), a condition known to elevate the risk of cardiovascular health issues. Despite recognition of the impact socioeconomic factors might have on a patient's course through the healthcare system, its association with cardiovascular outcomes post-RVO has not previously been thoroughly explored. DesignNationwide cohort study. MethodsWe included all subjects with RVO from the Danish nationwide registries diagnosed between 2000 and 2018. Information was combined using a personal identification number each Danish resident is given at birth or upon immigration. We categorized participants by their socioeconomic levels to evaluate the five-year incidence rate of cardiovascular conditions and overall mortality. The analysis was further refined by sex and age groups to elucidate any differential impacts. Furthermore, the cumulative incidence was estimated using the Aalen-Johansen estimator and the differences between the socioeconomic groups were quantified using a cox proportional hazard model. Key quantitative results were summarized, including hazard rate ratios (HR), confidence intervals (CI), and p-values ResultsThe cohort was comprised of 14,041 individuals with RVO. Our analysis revealed a relationship between educational attainment and cardiovascular health outcomes. Lower education levels were consistently linked with heightened risks of mortality, diabetes, ischemic heart disease, myocardial infarction, and peripheral artery disease following RVO. Individuals with a middle educational level also exhibited a higher prevalence of peripheral artery disease when compared to those with the highest education levels. In terms of income, the lowest earners faced increased risks across several categories, including mortality, diabetes, heart failure, ischemic heart disease, myocardial infarction, and peripheral artery disease, when compared to the highest-income earners. The middle-income group also showed elevated risks for mortality, heart failure, and peripheral artery disease. Being unmarried was additionally associated with higher risks of mortality and heart failure compared to being married. ConclusionSocioeconomic status was significantly associated with clinically relevant differences in post-RVO risk of cardiovascular diseases and death. Our data suggests that socioeconomic factors should be considered in the attempt to reduce the risk of cardiovascular disease and death in patients with RVO.

Risk of mortality and recurrence after first-time stroke among patients with type 2 diabetes: A Danish nationwide cohort study.

The prognosis for stroke patients with type 2 diabetes mellitus (T2DM) remains poorly understood. We examined the risk of mortality and stroke recurrence in stroke patients with T2DM and stroke patients without diabetes. We conducted a population-based cohort study including all patients diagnosed with a first-time ischemic stroke (n = 131,594) or intracerebral hemorrhage (ICH, n = 15,492) in Denmark, 2005-2021. Patients with T2DM were identified using hospital diagnosis codes and glucose-lowering drug prescriptions. We calculated risks, risk differences, and risk ratios, standardized by age, sex, and calendar year of stroke admission. Following ischemic stroke, the 5-year standardized mortality was 46.1% for patients with T2DM and 35.4% for patients without diabetes (standardized risk difference: 10.7% [95% CI 9.9-11.6]; risk ratio: 1.3 [95% CI 1.3-1.3]). The 5-year risk of recurrence following ischemic stroke was 12.7% for patients with T2DM and 11.3% for those without diabetes (risk difference: 1.4% [95% CI 0.9-2.0]; risk ratio: 1.1 [95% CI 1.1-1.2]). Following ICH, the 5-year mortality was 62.8% for patients with T2DM and 53.0% for patients without diabetes (risk difference: 9.8% [95% CI 7.2-12.4)]; risk ratio: 1.2 [95% CI 1.1-1.2]). The 5-year risk of recurrence after ICH was 9.1% for patients with T2DM and 9.7% for patients without diabetes. Stroke patients with T2DM were at increased risk of mortality. The risk of stroke recurrence was slightly higher for ischemic stroke patients with T2DM than patients without diabetes, while no difference was observed among ICH patients.

Cohort Profile: DOC*X-Generation-a nationwide Danish pregnancy cohort with OCcupational eXposure data.

Cohort Profile: DOC*X-Generation-a nationwide Danish pregnancy cohort with OCcupational eXposure data.

Recurrence patterns following nephrectomy for renal cell carcinoma in a Danish nationwide cohort.

This study aimed to characterize the demographic and clinical features of patients with renal cell carcinoma (RCC) post-surgery for localized or locally advanced disease in a national Danish cohort, with a specific focus on describing recurrence patterns in a subgroup aligned with the adjuvant KEYNOTE-564 trial classification. This was a retrospective analysis of the Danish Renal Cancer (DaRenCa) database. Eligible subjects were individuals with an RCC diagnosis between January 2014 and December 2017 who subsequently underwent radical or partial nephrectomy. Variables of interest were demographic and clinical characteristics, rates and sites of recurrence. Recurrence rates were also assessed in a subpopulation stratified using the risk classifications of the KEYNOTE-564 trial. A total of 2164 RCC patients were identified. Most patients (84.8%) had non-metastatic RCC (stage M0). A recurrence was observed in 250 of the M0 patients (13.6%). Patients with a recurrence were older, male, had a higher tumour stage, had undergone radical nephrectomy and had a higher Leibovich score. The majority (74.8%) of M0 patients had recurrence at distant metastatic sites. A total of 392 patients were stratified by the KEYNOTE-564 risk classification: 335 intermediate-high risk, 17 high risk and 40 M1 NED (metastatic with no evidence of disease). Recurrence was observed in 37.0%, 88.2% and 27.5% of these risk groups, respectively. This study elucidates the rates and determinants of post-surgical RCC recurrence in Denmark, underscoring the potential of adjuvant immunotherapy in refining therapeutic strategies, identifying suitable beneficiaries and minimizing overtreatment risks in RCC care.

Treatment of inflammatory bowel disease with steroid-sparing medications is age-dependent - Results from a Danish nationwide cohort study, 2000-2018.

Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges. We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD. All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications. 1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset. There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD.

Valproate Use During Spermatogenesis and Risk to Offspring

Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis. To evaluate the association between paternal use of valproate during spermatogenesis and offspring risk of congenital malformations and neurodevelopmental disorders. This nationwide cohort study included 1 235 353 singletons born in Denmark between January 1, 1997, and December 31, 2017, identified in the Medical Birth Register; 1336 children had fathers who had filled prescriptions for valproate during spermatogenesis. Congenital malformations were identified in the first year of life and neurodevelopmental disorders were identified from 1 year of age until December 31, 2018. Statistical analysis was performed March 2024. Paternal valproate exposure was defined as fathers who filled 1 or more prescriptions for valproate immediately before or during the time of spermatogenesis (ie, 3 months prior to conception). Children with major congenital malformations in the first year of life and with neurodevelopmental disorders before death or end of follow-up were identified in Danish health registers. Log-binomial regression was used to estimate adjusted relative risks (ARRs) of congenital malformations, and Cox proportional hazards regression was used to estimate adjusted hazards ratios (AHRs) of neurodevelopmental disorders, adjusted for relevant confounders. Among 1 235 353 live births (634 415 boys [51.4%] and 600 938 girls [48.6%]), 1336 children (0.1%) had fathers who filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years (IQR, 5.1-14.8 years) for valproate-exposed children and 10.3 years (IQR, 5.2-15.6 years) for valproate-unexposed children. A total of 43 903 children (3.6%) received a diagnosis of major congenital malformations in the first year of life, and 51 633 children (4.2%) received a diagnosis of neurodevelopmental disorders during follow-up. When comparing the risk among valproate-exposed children with that among unexposed children, the ARR of major congenital malformations was 0.89 (95% CI, 0.67-1.18), the AHR of neurodevelopmental disorders was 1.10 (95% CI, 0.88-1.37), and the AHR of autism spectrum disorder was 0.92 (95% CI, 0.65-1.30). In analyses addressing the robustness of the findings (ie, dose-response analyses, sibling analyses, analyses restricted to children of fathers with epilepsy, analyses that used children with paternal lamotrigine exposure as active comparator, and analyses that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure), there still was no increased risk of any of the included end points. In all analyses based on this large Danish cohort study, results suggest that exposure to valproate during spermatogenesis was not associated with offspring risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection

Background and aimsClostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. MethodsThis multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) eight weeks after the last FMT treatment. Secondary outcomes included CDAD cure one and eight weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. ResultsWe included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range (IQR) 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%, 95% confidence interval (CI) 71-79%) at week one. At week eight, 255 patients (55%, 95% CI 50-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%, 95% CI 75-82%). The 90-day mortality was 10% (95% CI 8-14%). ConclusionRepeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival.

Survival outcomes for metastatic castration sensitive prostate cancer: Real world data from a Danish cohort 2016-2022.

Survival outcomes for metastatic castration sensitive prostate cancer: Real world data from a Danish cohort 2016-2022.