Risk and prognosis of cancer in patients with obstructive uropathy compared with the general Danish population.

BACKGROUND: To examine whether obstructive uropathy is associated with increased risk of cancer and whether mortality differs between cancer patients with and without obstructive uropathy. METHODS: In a nationwide population-based Danish cohort study including 37,275 adult patients with a first-time hospital-related diagnosis of obstructive uropathy in 1996-2022, we assessed cumulative cancer incidence (risk) and standardized incidence ratios (SIRs). Furthermore, we compared the mortality of 7,485 patients diagnosed with cancer after obstructive uropathy diagnosis with that of 69,785 cancer patients without obstructive uropathy matched by age, sex, cancer site, stage, and calendar year of cancer diagnosis. RESULTS: 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-<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. CONCLUSIONS: 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. IMPACT: These findings can inform the follow-up recommendations for obstructive uropathy.

Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

OBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 high- and middle-income countries. POPULATION: Live births and stillbirths. METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth. RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

Association of Autoimmune Diseases With Coronary Atherosclerosis Severity and Ischemic Events.

BACKGROUND: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. OBJECTIVES: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. METHODS: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. RESULTS: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). CONCLUSIONS: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.

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

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.

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

BACKGROUND: Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We therefore conducted a population-based cohort study using healthcare databases of the Danish population (January 1980-December 2022). We followed 87,507 people for a median of 10.1 years after first hospital contact for urticaria. OBJECTIVES: To examine associations of a hospital diagnosis of urticaria with incident cancer. METHODS: We computed 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. RESULTS: The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11) based on 7,788 observed vs. 7,161 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 7,200 people thereafter (SIR 1.06, 95% CI, 1.04-1.09). During the first year of follow-up, we found strong associations with hematological cancers (e.g., non-Hodgkin lymphoma SIR 2.91, 95% CI, 1.92-4.23). Cancer stage was similar in people with vs. without previous urticaria diagnosis. CONCLUSIONS: At the time of urticaria diagnosis, or in the first year afterwards, we found a large increase in the risk for 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.

Longitudinal HbA1c patterns before the first treatment of diabetes in routine clinical practice: A latent class trajectory analysis.

AIMS: To examine the longitudinal heterogeneity of HbA1c preceding the initiation of diabetes treatment in clinical practice. METHODS: In this population-based study, we used HbA1c from routine laboratory and healthcare databases. Latent class trajectory analysis was used to classify individuals according to their longitudinal HbA1c patterns before first glucose-lowering drug prescription irrespective of type of diabetes. RESULTS: Among 21,556 individuals initiating diabetes treatment during 2017-2018, 20,733 (96 %) had HbA1c measured (median 4 measurements [IQR 2-7]) in the 5 years preceding treatment initiation. Four classes with distinct HbA1c trajectories were identified, with varying steepness of increase in HbA1c. The largest class (74 % of the individuals) had mean HbA1c above the 48 mmol/mol threshold 9 months before treatment initiation. Mean HbA1c was 52 mmol/mol (95 % CI 52-52) at treatment initiation. In the remaining three classes, mean HbA1c exceeded 48 mmol/mol almost 1.5 years before treatment initiation and reached 79 mmol/mol (95 % CI 78-80), 105 mmol/mol (95 % CI 104-106), and 137 mmol/mol (95 % CI 135-140) before treatment initiation. CONCLUSION: We identified four distinct longitudinal HbA1c patterns before initiation of diabetes treatment in clinical practice. All had mean HbA1c levels exceeding the diagnostic threshold many months before treatment initiation, indicating therapeutic inertia.

Randomized comparison of TAVI valves: The Compare-TAVI trial.

INTRODUCTION: Based on technical advancements and clinical evidence, transcatheter aortic valve implantation (TAVI) has been widely adopted. New generation TAVI valve platforms are continually being developed. Ideally, new valves should be superior or at least non-inferior regarding efficacy and safety, when compared to best-in-practice contemporary TAVI valves. METHODS AND ANALYSIS: The Compare-TAVI trial (ClinicalTrials.gov NCT04443023) was launched in 2020, to perform a 1:1 randomized comparison of new vs contemporary TAVI valves, preferably in all comers. Consecutive cohorts will be launched with sample sizes depending on the choice of interim analyses, expected event rates, and chosen superiority or non-inferiority margins. Enrollment has just been finalized in cohort B, comparing the Sapien 3/Sapien 3 Ultra Transcatheter Heart Valve (THV) series (Edwards Lifesciences, Irvine, California, USA) and the Myval/Myval Octacor THV series (Meril Life Sciences Pvt. Ltd., Vapi, Gujarat, India) balloon expandable valves. This non-inferiority study was aimed to include 1062 patients. The 1-year composite safety and efficacy endpoint comprises death, stroke, moderate-severe aortic regurgitation, and moderate-severe valve deterioration. Patients will be followed until withdrawal of consent, death, or completion of 10-year follow-up, whichever comes first. Secondary endpoints will be monitored at 30 days, 1, 3, 5, and 10 years. SUMMARY: The Compare-TAVI organization will launch consecutive cohorts wherein patients scheduled for TAVI are randomized to one of two valves. The aim is to ensure that the short- and long-term performance and safety of new valves being introduced is benchmarked against what achieved by best-in-practice contemporary valves.

Evaluation of Left Truncation and Censoring When Changing the Use of the International Classification of Diseases Eighth Revision Codes to Tenth Revision Codes in the Danish National Patient Registry.

Purpose: In the Danish National Patient Registry (DNPR), covering all Danish hospitals and widely used in research, diseases have been recorded using International Classification of Diseases (ICD) codes, transitioning from the Eighth to the Tenth revision in 1994. Uncertainty exists regarding whether including ICD-8 codes alongside ICD-10 is needed for complete disease identification. We assessed the extent of left-truncation and left-censoring in the DNPR arising from omitting ICD-8 codes. Patients and Methods: We sampled 500,000 Danes ≥40 years of age in 1995, 2010, and 2018. From the DNPR, we identified cardiovascular, endocrine, gastrointestinal, neurological, pulmonary, rheumatic, and urogenital diseases as well as fractures. We obtained the number of people with a disease recorded with ICD-8 codes only (ie, the ICD-8 record would be left-truncated by not using ICD-8 codes), ICD-8 plus ICD-10 codes (ie, the ICD-8 record would be left-censored by not using ICD-8 codes), and ICD-10 codes only. For each ICD group, we calculated the proportion of people with the disease relative to the total sample (ie, 500,000 people) and the total number of people with the disease across all ICD groups. Results: Overall, the left-truncation issue decreased over the years. Relative to all people with a disease, the left-truncated proportion was for example 59% in 1995 and <2% in 2018 for diabetes mellitus; 93% in 1995, and 54% in 2018 for appendicitis. The left-truncation issue increased with age group for most diseases. The proportion of disease records left-censored by not using ICD-8 codes was generally low but highest for chronic diseases. Conclusion: The left-truncation issue diminished over sample years, particularly for chronic diseases, yet remained rather high for selected surgical diseases. The left-truncation issue increased with age group for most diseases. Left-censoring was overall a minor issue that primarily concerned chronic diseases.

Validation of algorithms in studies based on routinely collected health data: general principles.

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. This paper aims to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy; gold/reference standard; study size; prioritizing accuracy measures; algorithm portability; and implication for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome or covariate). Validation work should be part of routine maintenance of RWD sources.

Outcome of pregnancy oral glucose tolerance test and preterm birth.

BACKGROUND: Gestational diabetes is associated with adverse outcomes such as preterm birth (<37 weeks). However, there is no international consensus on screening criteria or diagnostic levels for gestational diabetes, and it is unknown whether body mass index (BMI) or obesity modifies the relation between glucose level and preterm birth. METHODS: We studied a pregnancy cohort restricted to two Danish regions from the linked Danish Medical Birth Register to study associations between glucose measurements from the 2-hour post-load 75-gram oral glucose tolerance test (one-step approach) and preterm birth from 2004-2018. In Denmark, gestational diabetes screening is a targeted strategy for mothers with identified risk factors. We used Poisson regression to estimate rate ratios (RR) of preterm birth with z-standardized glucose measurements. We assessed effect measure modification by stratifying analyses and testing for heterogeneity. RESULTS: Among 11,337 pregnancies (6.2% delivered preterm), we observed an adjusted preterm birth RR of 1.2 (95% CI: 1.1-1.3) for a 1 standard deviation glucose increase of 1.4 mmol/L from the mean 6.7 mmol/L. There was evidence for effect measure modification by obesity, e.g., adjusted RR for non-obese (BMI <30): 1.2 (95%CI: 1.1-1.3) vs. obese (BMI ≥30): 1.3 (95%CI: 1.2-1.5), P=0.05 for heterogeneity. CONCLUSIONS: Among mothers screened for gestational diabetes, increased glucose levels, even those below the diagnostic level for gestational diabetes in Denmark, were associated with increased preterm birth risk. Obesity (BMI ≥30) may be an effect measure modifier, not just a confounder, of the relation between blood glucose and preterm birth risk.

Major comorbid diseases as predictors of infection in the first month after hip fracture surgery: a population-based cohort study in 92,239 patients.

PURPOSE: Comorbidity level is a predictor of infection in the first 30 days after hip fracture surgery. However, the roles of individual comorbid diseases as predictors of infection remain unclear. We investigated individual major comorbid diseases as predictors of infection after hip fracture surgery. METHODS: We obtained Danish population-based medical registry data for patients undergoing hip fracture surgery (2004-2018). Information was obtained on 27 comorbidities, included in various comorbidity indices, 5 years before surgery. The primary outcome was any hospital-treated infection within 30 days after surgery. Cumulative incidence of infection was calculated by considering death as competing risk. We used logistic regression to compute mutually adjusted odds ratios with 95% confidence interval for infection. RESULTS: Of 92,239 patients with hip fracture, 71% were women, and the median age was 83 years. The most prevalent comorbidities were hypertension (23%), heart arrhythmia (15%), and cerebrovascular disease (14%). The 30-day incidence of infection was 15% and 12% among the total cohort and among patients with no record of comorbidities, respectively. Infection incidence was highest among patients with renal disease (24%), depression/anxiety (23%), and chronic pulmonary disease (23%), and lowest among patients with metastatic solid tumor (15%). Adjusted odds ratios of infection ranged from 0.94 [0.80-1.10] for metastatic solid tumor to 1.77 [1.63-1.92] for renal disease. CONCLUSION: Most comorbid diseases were predictors of infection after surgery for hip fracture. Awareness of patients' comorbidity profiles might help clinicians initiate preventive measures or inform patients of their expected risk.

Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study.

Aim: To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI). Methods: Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010-2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (<3.0 vs ≥3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death). Results: We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11-1.32) overall, 1.19 (1.06-1.33) in the low LDL-C group, and 1.23 (1.07-1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07-1.39) in the low LDL-C group and 1.54 (1.30-1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results. Conclusion: In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death.

Semaglutide (Ozempic®) Use in Denmark 2018 Through 2023 ‒ User Trends and off-Label Prescribing for Weight Loss.

Purpose: A surge in the use of semaglutide injection (Ozempic®) approved to treat type 2 diabetes (T2D) has led to a global supply shortage. We investigated contemporary user rates and clinical characteristics of semaglutide (Ozempic®) users in Denmark, and the extent of "off-label" prescribing for weight loss. Patients and Methods: Nationwide population-based cross-sectional study based on linked health registries January 2018 through December 2023. All adults who received a first prescription of semaglutide once weekly (Ozempic®) were included. We examined quarterly rates of new users and total user prevalences, using other glucagon-like peptide-1 receptor agonists and weight loss medications as comparison. We also investigated user characteristics including T2D, glucose control, comedications, and cardiorenal disease. Results: The new user rate of semaglutide (Ozempic®) remained stable at approximately 4 per 1000 adult person-years between 2019 and 2021 and then accelerated, peaking at 10 per 1000 in the first quarter of 2023 after which it declined sharply. User prevalence increased to 91,626 users in Denmark in 2023. The proportion of semaglutide (Ozempic®) new users who had a record of T2D declined from 99% in 2018 to only 67% in 2022, increasing again to 87% in 2023. Among people with T2D who initiated semaglutide (Ozempic®) in 2023, 52% received antidiabetic polytherapy before initiation, 39% monotherapy, and 8% no antidiabetic therapy. Most T2D initiators had suboptimal glucose control, with 83% having an HbA1c ≥48 mmol/mol and 68% ≥53 mmol/mol despite use of antidiabetic medication, and 29% had established atherosclerotic cardiovascular disease or kidney disease. Conclusion: The use of semaglutide (Ozempic®) in Denmark has increased dramatically. Although not approved for weight loss without T2D, one-third of new users in 2022 did not have T2D. Conversely, most initiators with T2D had a clear medical indication for treatment intensification, and "off-label" use can only explain a minor part of the supply shortage.

Enhancing the data capture of periprosthetic joint infections in the Danish Knee Arthroplasty Registry: validity assessment and incidence estimation.

BACKGROUND AND PURPOSE: Revisions due to periprosthetic joint infection (PJI) are underestimated in national arthroplasty registries. Our primary objective was to assess the validity in the Danish Knee Arthroplasty Register (DKR) of revisions performed due to PJI against the Healthcare-Associated Infections Database (HAIBA). The secondary aim was to describe the cumulative incidences of revision due to PJI within 1 year of primary total knee arthroplasty (TKA) according to the DKR, HAIBA, and DKR/HAIBA combined. METHODS: This longitudinal observational cohort study included 56,305 primary TKAs (2010-2018), reported in both the DKR and HAIBA. In the DKR, revision performed due to PJI was based on pre- and intraoperative assessment disclosed by the surgeon immediately after surgery. In HAIBA, PJI was identified from knee-related revision procedures coinciding with 2 biopsies with identical microbiological pathogens. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of revision due to PJI in the DKR (vs. HAIBA, within 1 year of TKA) with 95% confidence intervals (CI). Cumulative incidences were calculated using the Kaplan-Meier method. RESULTS: The DKR's sensitivity for PJI revision was 58% (CI 53-62) and varied by TKA year (41%-68%) and prosthetic type (31% for monoblock; 63% for modular). The specificity was 99.8% (CI 99.7-99.8), PPV 64% (CI 62-72), and NPV 99.6% (CI 99.6-99.7). 80% of PJI cases not captured by the DKR were caused by non-reporting rather than misclassification. 33% of PJI cases in the DKR or HAIBA were culture-negative. Considering potential misclassifications, the best-case sensitivity was 64%. The cumulative incidences of PJI were 0.8% in the DKR, 0.9% in HAIBA, and 1.1% when combining data. CONCLUSION: The sensitivity of revision due to PJI in the DKR was 58%. The cumulative incidence of PJI within 1 year after TKA was highest (1.1%) when combining the DKR and HAIBA, showing that incorporating microbiology data into arthroplasty registries can enhance PJI validity.

Use of Latent Class Analysis to Predict Intensive Care Unit Admission and Mortality in Children with a Major Congenital Anomaly.

OBJECTIVE: To define major congenital anomaly (CA) subgroups and assess outcome variability based on defined subgroups. STUDY DESIGN: This population-based cohort study used registries in Denmark for children born with a major CA between January 1997 and December 2016, with follow-up until December 2018. We performed a latent class analysis (LCA) using child and family clinical and sociodemographic characteristics present at birth, incorporating additional variables occurring until age of 24 months. Cox proportional hazards regression models estimated hazard ratios (HRs) of pediatric mortality and intensive care unit (ICU) admissions for identified LCA classes. RESULTS: The study included 27 192 children born with a major CA. Twelve variables led to a 4-class solution (entropy = 0.74): (1) children born with higher income and fewer comorbidities (55.4%), (2) children born to young mothers with lower income (24.8%), (3) children born prematurely (10.0%), and (4) children with multiorgan involvement and developmental disability (9.8%). Compared with those in Class 1, mortality and ICU admissions were highest in Class 4 (HR = 8.9, 95% CI = 6.4-12.6 and HR = 4.1, 95% CI = 3.6-4.7, respectively). More modest increases were observed among the other classes for mortality and ICU admissions (Class 2: HR = 1.7, 95% CI = 1.1-2.5 and HR = 1.3, 95% CI = 1.1-1.4, respectively; Class 3: HR = 2.5, 95% CI = 1.5-4.2 and HR = 1.5, 95% CI = 1.3-1.9, respectively). CONCLUSIONS: Children with a major CA can be categorized into meaningful subgroups with good discriminative ability. These groupings may be useful for risk-stratification in outcome studies.

Lifetime and 10-year cardiovascular risk prediction in individuals with type 1 diabetes: The LIFE-T1D model.

AIMS: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. MATERIALS AND METHODS: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. RESULTS: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. CONCLUSIONS: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation.

Risk and adverse clinical outcomes of thrombocytopenia among patients with solid tumors-a Danish population-based cohort study.

BACKGROUND: Knowledge about thrombocytopenia among patients with solid tumors is scarce. We examined the risk of thrombocytopenia among patients with solid tumors and its association with adverse outcomes. METHODS: Using Danish health registries, we identified all patients with incident solid tumors from 2015-2018 (n = 52,380) and a platelet count measurement within 2 weeks prior to or on their cancer diagnosis date. The risk of thrombocytopenia was categorized as grades 0 (any platelet count × 109/L): <150; 1: <100; 2: <75; 3: <50; 4: <25, and 5: <10. To study the outcomes, each patient with thrombocytopenia was matched with up to five cancer patients without thrombocytopenia by age, sex, cancer type, and stage. Cox regression was used to compute hazard ratios (HRs) of bleeding, transfusion, or death, adjusting for confounding factors. RESULTS: The 1-year risk of thrombocytopenia was 23%, increasing to 30% at 4 years. This risk was higher in patients receiving chemotherapy (43% at 1 year and 49% at 4 years). Overall, patients with thrombocytopenia had higher 30-days rates of bleeding (HR = 1.72 [95% confidence interval, CI: 1.41-2.11]). Thrombocytopenia was also associated with an increased rate of transfusion, and death, but some of the risk estimates were imprecise. CONCLUSIONS: The risk of thrombocytopenia was substantial among patients with solid tumors and associated with adverse outcomes.

Critical evaluation of cohort study results.

Being able to critically evaluate modern cohort studies is important when being presented with claims based on observational evidence. In this review article, key aspects of the cohort design are presented using an example of a cohort study investigating the association between the use of SGLT2 inhibitors and gout. We describe the active comparator, new user design, modern methods used to address confounding, how to identify the most common sources of bias, and how to interpret study results appropriately.

Critical evaluation of articles on case-control studies.

The case-control design is one of the key designs used in observational research. In this review, we discuss common pitfalls of case-control studies and describe how case-control studies can be critically evaluated. We further assert that a well-conducted case-control study provides the same results, precision, and level of evidence as a corresponding cohort study.

Association between maternal employment status and presence of children with major congenital anomalies in Denmark.

IMPORTANCE: The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. OBJECTIVE: To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. DESIGN: A population-based matched cohort study. SETTING: Denmark. PARTICIPANTS: All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant's year of birth (n = 234,586). EXPOSURES: Liveborn infant with a major congenital anomaly. MAIN OUTCOMES AND MEASURES: The primary outcome was mothers' employment status, stratified by their child's age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child's age (i.e., 0-1 year, > 1-6 years, 7-13 years, 14-18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant's year of birth. RESULTS: During 1-6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6-107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4-98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04-1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06-1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1-6 years after delivery (ARR, 1.05; 95% CI, 1.04-1.07), 9% higher during 7-13 years after delivery (ARR, 1.09; 95% CI, 1.06-1.12), and 12% higher during 14-18 years after delivery (ARR, 1.12; 95% CI, 1.07-1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89-3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29-2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11-1.29]. CONCLUSION AND RELEVANCE: MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.