Proton pump inhibitors and the risk of acute kidney injury in cancer patients receiving immune checkpoint inhibitors: A Danish population-based cohort study.

Previous studies have suggested that the use of proton pump inhibitors (PPIs) more than doubles the risk of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs). However, this association may be confounded. Therefore, we conducted a register-based cohort study to examine the risk of AKI in users and nonusers of PPIs among cancer patients treated with ICIs in Denmark from 2011 through 2021 while accounting for a comprehensive range of potential confounders. PPI use was determined based on redeemed prescriptions of PPIs before ICI initiation. We identified laboratory-recorded AKI events within the first year after ICI initiation. We estimated the risks and hazard ratios (HRs) of AKI while accounting for a comprehensive range of confounders (including comorbidities and comedication) by propensity score weighting. Furthermore, we performed an additional per-protocol analysis while accounting for informative censoring by weighting. We identified 10 200 cancer patients including 2749 (27%) users, 6214 (61%) nonusers, and 1237 (12%) former users of PPIs. PPI users had an increased risk of AKI compared to nonusers (1-year risk, 24.7% vs 19.9%; HR, 1.42 [95% confidence interval (CI), 1.29-1.56]); however, this association attenuated when accounting for confounders (weighted 1-year risk, 24.2% vs 23.8%; weighted HR, 1.06 [95% CI, 0.93-1.21]). In the per-protocol analysis, the crude HR was 1.86 (95% CI, 1.63-2.12), while the weighted HR was 1.24 (95% CI, 1.03-1.49). Thus, the association between PPI use and AKI could largely be explained by confounding, suggesting that previous studies may have overestimated the association.

Platelet response to romiplostim amongst patients with newly diagnosed, persistent, and chronic immune thrombocytopenia in routine clinical practice in Denmark, Sweden, and Norway.

Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim-exposed adults with ITP lasting ≥6 months during 2009-2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 109/L at 14-24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3-12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75-76 × 109/L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 109/L, 68 × 109/L, and 71 × 109/L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation.

Rheumatoid arthritis and risk of osteoarticular infection and death following Staphylococcus aureus bacteraemia: A nationwide cohort study.

OBJECTIVES: Osteoarticular infection (OAI) is a feared complication of Staphylococcus aureus bacteraemia (SAB) and is associated with poor outcomes. We aimed to explore risk of OAI and death following SAB in patients with and without rheumatoid arthritis (RA) and to identify risk factors for OAI in patients with RA. METHODS: Danish nationwide cohort study of all patients with microbiologically verified first-time SAB between 2006-2018. We identified RA, SAB, comorbidities, and RA-related characteristics (e.g. orthopaedic implants, antirheumatic treatment) in national registries including the rheumatology registry DANBIO. We estimated cumulative incidence of OAI and death and adjusted hazard ratios (HRs, multivariate Cox regression). RESULTS: We identified 18 274 patients with SAB (n = 367 with RA). The 90-day cumulative incidence of OAI was 23.1%(95%CI 18.8; 27.6) for patients with RA and 12.5%(12.1; 13.0) for patients without RA (non-RA) (HR 1.93(1.54; 2.41)). For RA patients with orthopaedic implants cumulative incidence was 29.4%(22.9; 36.2) (HR 1.75(1.08; 2.85), and for current users of tumor necrosis factor inhibitors (TNFi) it was 41.9%(27.0; 56.1) (HR 2.27(1.29; 3.98) compared with non-users). All-cause 90-day mortality following SAB was similar in RA (35.4%(30.6; 40.3)) and non-RA (33.9%(33.2; 34.5), HR 1.04(0.87; 1.24)). CONCLUSION: Following SAB, almost one in four patients with RA contracted OAI corresponding to a doubled risk compared with non-RA. In RA, orthopaedic implants and current TNFi use were associated with approximately doubled OAI risk. One in three died within 90 days in both RA and non-RA. These findings encourage vigilance in RA patients with SAB to avoid treatment delay of OAI.

The one-year infection risk among patients diagnosed with giant cell arteritis: use of antibiotics and hospitalisations.

OBJECTIVES: Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA. METHODS: This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996-2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD), and relative risks (RR) of infections. RESULTS: The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7-53.2) for overall infections and 17.6% (95% CI: 17.1-18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38-1.42) for overall infections and 2.71 (95% CI: 2.61-2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years), and higher comorbidity were associated with an increased risk of infections among patients with GCA. CONCLUSIONS: The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk.

Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

OBJECTIVE: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. METHODS: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. RESULTS: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. INTERPRETATION: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562.

Fifteen-year temporal changes in rates of acute kidney injury among children in Denmark.

BACKGROUND: We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. METHODS: In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0-17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. RESULTS: In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141-155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161-187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118-140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141-155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period. CONCLUSION: The rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time.

Acute urinary retention in men: 21-year trends in incidence, subsequent benign prostatic hyperplasia-related treatment and mortality: A Danish population-based cohort study.

OBJECTIVE: To examine trends in incidence of acute urinary retention, subsequent benign prostatic hyperplasia-related treatment and mortality in the era of medical therapy for benign prostatic hyperplasia. Additionally, to compare mortality with the general population. MATERIALS AND METHODS: We conducted a Danish nationwide registry-based study including 70,775 men aged 45 years or older with a first hospitalization for acute urinary retention during 1997-2017. We computed annual standardized incidence rates, subsequent 1-year cumulative incidence of benign prostatic hyperplasia-related surgical and medical treatment, and standardized 3-month and 1-year mortality rates. Finally, we compared standardized all-cause and cause-specific mortality ratios with the general population. RESULTS: The standardized incidence rate of acute urinary retention per 1000 person-years increased transiently from 2.34 to 3.42 during 1997-2004, but gradually declined to 2.95 in 2017. The 1-year cumulative incidence of benign prostatic hyperplasia-related surgery declined from 31.2% to 19.8% and 20.5% to 7.7% after spontaneous and precipitated acute urinary retention, respectively. During 1997-2017, the standardized 1-year mortality declined from 22.2% to 17.2%. Compared with the general population, mortality was 4-5 times higher after 3 months and 2-3 times higher after 1 year of acute urinary retention. The cause-specific standardized mortality ratios were particularly high for deaths attributable to malignancies, urogenital disease, certain infections, chronic pulmonary disease, and diabetes. CONCLUSION: During 1997-2017, we observed a transient increase in the incidence of acute urinary retention. The subsequent use of benign prostatic hyperplasia-related surgery declined considerably and mortality continued to be high, mainly because of deaths from malignancies, urogenital disease, infections, and preexisting comorbidity.

Long-term risk of benign prostatic hyperplasia-related surgery and acute urinary retention in men treated with 5-alpha reductase inhibitor versus alpha-blocker monotherapy in routine clinical care.

OBJECTIVES: To assess the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR) in men treated with 5-alpha-reductase inhibitor (5-ARI) versus alpha-blocker monotherapy in routine clinical care over 15 years of follow-up. METHODS: Using population-based Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after the date of first prescription and included men who redeemed at least one additional prescription before the index date. We used multiple imputation to replace missing prostate-specific antigen values. We performed propensity score-weighted Cox regression to estimate weighted hazard ratios (wHRs) and cumulative incidence function to estimate weighted cumulative risks of BPH-related surgery and AUR in intention to treat (ITT) and per protocol (PP) analyses. RESULTS: We included 18,421 and 95,984 men treated with 5-ARI and alpha-blocker monotherapy, respectively. Overall, treatment with 5-ARI monotherapy was associated with a reduced risk of BPH-related surgery (ITT wHR = 0.73 (95% confidence interval [CI]: 0.68-0.78), PP wHR = 0.77 (95% CI: 0.70-0.84) and AUR (ITT wHR = 0.73 (95% CI: 0.67-0.78), PP wHR = 0.75 (95% CI: 0.66-0.84). The 15-year risk of BPH-related surgery in men treated with 5-ARI versus alpha-blocker monotherapy was 14.8% (95% CI: 14.1%-15.5%) versus 19.1% (95% CI: 18.7%-19.5%) in the ITT analysis and 13.8% (95% CI: 12.6%-14.9%) versus 17.5% (95% CI: 16.9%-18.0%) in the PP analysis. The 15-year risk of AUR in men treated with 5-ARI versus alpha-blocker was 13.0% (95% CI: 12.3%-13.6%) versus 16.6% (95% CI: 16.3%-17.0%) in the ITT analysis and 12.6% (95%: 11.3%-14.0%) versus 16.9% (95% CI: 16.3%-17.6%) in the PP analysis. CONCLUSION: Treatment with 5-ARI versus alpha-blocker monotherapy in routine clinical care was associated with a reduced risk of BPH-related surgery and AUR for up to 15 years of follow-up. After 15 years of follow-up, the relative risk reduction was 21%-25% and the absolute risk reduction was 4%.

Cost of non-communicable diseases in people living with HIV in the Central Denmark Region.

OBJECTIVE: To estimate the economic burden of non-communicable diseases (NCDs) in people living with HIV (PLWH) in Denmark. METHODS: We conducted a cohort study using population-based Danish medical registries including all adult residents of the Central Denmark Region registered with a first-time HIV-diagnosis during the period 2006-2017. For each PLWH, we matched 10 persons without HIV from the background population by birth year, sex and municipality of residence. Information on healthcare utilization and costs for the PLWH and non-HIV cohorts was retrieved from register data. For each cohort, we estimated the annual costs for major disease categories (HIV care, other somatic care, and psychiatric care) in the period from 3 years before to 9 years after diagnosis/matching date. RESULTS: We identified 407 PLWH and 4070 persons from the background population. The total healthcare costs during the study period were approximately three times higher for PLWH compared to the non-HIV cohort (€76 198 vs. €23 692). Average annual cost of hospital care, primary care and selected prescription medicine was estimated to be €6987 per year in the years after the diagnosis compared to €2083 per year in the non-HIV cohort. In PLWH, the cost of NCDs and psychiatric care was approximately two times higher than the cost of HIV care. CONCLUSION: PLWH have higher healthcare costs stemming from three areas: excess cost due to the HIV infection, the treatment of NCDs, and psychiatric care.

Prenatal Antidepressant Exposure and the Risk of Attention-Deficit/Hyperactivity Disorder in Childhood: Accounting for Misclassification of Exposure.

BACKGROUND: Many studies of prenatal antidepressant exposure and the risk of attention-deficit/hyperactivity disorder (ADHD) have done little to reduce bias from exposure misclassification. We assessed the prenatal antidepressant-ADHD effect by incorporating information on repeatedly redeemed prescriptions and redemptions of drug classes commonly used in pregnancy in the analyses to reduce bias from exposure misclassification. METHODS: Using population-based registries, we conducted a nationwide cohort study of all children born in Denmark from 1997 to 2017. In a former-user analysis, we compared children prenatally exposed, defined by a redeemed prescription by the mother during pregnancy, to a comparison cohort consisting of prenatally unexposed children whose mothers had redeemed a prescription before pregnancy. We incorporated information on repeatedly redeemed prescriptions and redemptions of drug classes commonly used in pregnancy in the analyses to reduce bias from exposure misclassification. We used incidence rate ratios (IRRs) and incidence rate differences (IRDs) as effect measures. RESULTS: The cohort included 1,253,362 children, among whom 24,937 were prenatally exposed to antidepressants. The comparison cohort consisted of 25,698 children. During follow-up, 1,183 exposed children and 1,291 children in the comparison cohort developed ADHD yielding an IRR of 1.05 (95% confidence interval [CI] = 0.96, 1.15) and an IRD of 0.28 (95% CI = -0.20, 0.80) pr. 1,000 person-years. IRRs from analyses attempting to reduce exposure misclassification varied from 1.03 to 1.07. CONCLUSIONS: Our results were not consistent with the hypothesized effect of prenatal antidepressant exposure on the risk of ADHD. Attempts to reduce exposure misclassification did not alter this finding.

Treatment patterns, survival, and healthcare utilisation and costs in patients with locally advanced and metastatic bladder cancer in Denmark 2015-2020.

BACKGROUND: Treatment patterns in locally advanced and metastatic urothelial bladder cancer (La/mUBC) is changing, but little is known about current treatment patterns, survival, and costs of these patients. Our aim was to describe treatment patterns, survival, and healthcare utilisation/costs in Danish La/mUBC patients in a routine clinical care setting. METHODS: Registry-based nationwide cohort study including all bladder cancer patients aged 18 years or older with a La/mUBC tumour in the pathology register and a concomitant bladder cancer diagnosis in the Danish National Patient Registry in the period 2015-2020. We categorised the patients according to (1) La/mUBC at time of first bladder cancer diagnosis (de novo La/mUBC) and (2) non-invasive or localised muscle-invasive bladder cancer at time of diagnosis which had progressed to La/mUBC. All patients were included at date of pathology-confirmed La/mUBC. Follow-up ended 30 September 2022. RESULTS: We identified 1278 patients (69% men) with La/mUBC and no other previous cancer. Of these, 212 (17%) had de novo La/mUBC, while 1066 (83%) had progressed to La/mUBC. Median age was 72 years. Patients were followed for a median of 13.0 months (interquartile range 4.7;32.0). During follow-up, 651 (51%) patients started first-line treatment, of these, 285 progressed to second-line treatment, and 112 also started third-line treatment. Median survival was 13.0 months from La/mUBC diagnosis, 12.1 months from start of first-line treatment, 9.8 months from start of second-line treatment, and 8.6 months from start of third-line treatment. The mean number of days admitted to hospital was 3.47, 3.97, and 4.07 per month following initiation of first-line, second-line, and third-line treatment, respectively. CONCLUSION: Patients with La/mUBC have a poor prognosis, and in routine clinical care only around half of the patients received systemic anti-cancer treatment suggesting an unmet need for novel treatments. The overall costs only increased slightly from first to third-line treatment.

Musculoskeletal Diagnoses before Cancer in Children: A Danish Registry-Based Cohort Study.

OBJECTIVE: To identify the prevalence of musculoskeletal diagnoses recorded 6 months before the diagnosis of cancer and to evaluate whether preceding musculoskeletal diagnoses affected survival. STUDY DESIGN: We performed a nationwide registry-based cohort study including all children under 15 years of age diagnosed with cancer in Denmark over a 23-year period (1996-2018). The Danish National Patient Registry was used to identify musculoskeletal diagnoses and associated dates recorded within 6 months preceding the diagnosis of cancer. We compared the characteristics of children with and without a prior musculoskeletal diagnoses using prevalence ratios and 95% CI and diagnostic interval as median with IQR. We compared survival using Kaplan-Meier and Cox proportional hazards regression analysis adjusting for age, sex, and presence of metastasis at diagnosis. RESULTS: Of 3895 children with all types of cancer, 264 (7%) had a total of 451 hospital visits with musculoskeletal diagnosis within 6 months preceding the diagnosis of cancer; however, survival was not affected. The overall median diagnostic interval from first musculoskeletal diagnosis (within 6 months before cancer diagnosis) to cancer diagnosis was 15 days (IQR, 7-47 days). A diagnosis of juvenile idiopathic arthritis, unspecified arthritis, and arthropathy each accounted for 5% of the contacts, primarily in children with acute lymphoblastic leukemia, bone sarcomas, or neuroblastomas. CONCLUSIONS: A preliminary musculoskeletal diagnosis occurred in 7% of children with cancer, but did not affect the overall survival.

All-cause and cause-specific mortality in patients with giant cell arteritis: a nationwide, population-based cohort study.

OBJECTIVES: To investigate whether GCA is associated with increased all-cause and cause-specific mortality. METHODS: A nationwide, population-based cohort study in Denmark using medical and administrative registries. GCA cases were defined as patients aged ≥50 years from 1996-2018 with a first-time discharge diagnosis of GCA and ≥3 prescriptions for prednisolone within 6 months following diagnosis. Each GCA patient was matched based on age, sex and calendar time to 10 persons without a history of GCA. Index date was the date for the third prednisolone prescription. We used a pseudo-observation approach to calculate all-cause and cause-specific mortality, adjusted risk differences (RDs) and relative risks (RRs). RESULTS: We included 9908 GCA patients and 98 204 persons from the general population. The median time for GCA patients to redeem the third prednisolone prescription was 74 days [interquartile range (IQR: 49-106)]. Among GCA patients, the overall mortality was 6.4% (95% CI: 5.9, 6.9) 1 year after index date and 45% (95% CI: 44, 47) after 10 years. Compared with the reference cohort, adjusted RDs and RRs of deaths in the GCA cohort were 2.2% (95% CI: 1.7, 2.7) and 1.49 (95% CI: 1.36, 1.64) after 1 year, and 2.1% (95% CI: 1.0, 3.3) and 1.03 (95% CI: 1.00, 1.05) 10 years after index date. GCA patients had a higher risk of death due to infectious, endocrine, cardiovascular and gastrointestinal diseases. CONCLUSIONS: GCA is associated with increased all-cause mortality, particularly within the first year following the diagnosis. Cause-specific mortality indicates that mortality in GCA may in part be due to glucocorticoid-related complications.

Increased risk of thoracic aortic complications among patients with giant cell arteritis: a nationwide, population-based cohort study.

OBJECTIVE: To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA. METHODS: In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk. RESULTS: We included 9908 GCA patients and 98 204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4-2.2), 1.0% (0.7-1.2) and 4.8% (4.2-5.3). Compared with the referents, the 15-year RR were 11.2 (7.41-16.9) for thoracic AA, 6.86 (4.13-11.4) for AD, 1.04 (0.83-1.32) for abdominal AA and 1.53 (1.35-1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4-11.2) with a number needed to be screened of 250 (167-333), 91 (71-111) and 53 (45-67) after 5, 10 and 15 years. CONCLUSION: Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA.

Prognostic and discriminative accuracy of the quick Sepsis-related Organ Failure Assessment compared with an early warning score: a Danish cohort study.

BACKGROUND: The clinical benefit of implementing the quick Sepsis-related Organ Failure Assessment (qSOFA) instead of early warning scores (EWS) to screen all hospitalised patients for critical illness has yet to be investigated in a large, multicentre study. METHODS: We conducted a cohort study including all hospitalised patients ≥18 years with EWS recorded at hospitals in the Central Denmark Region during the year 2016. The primary outcome was intensive care unit (ICU) admission and/or death within 2 days following an initial EWS. Prognostic accuracy was examined using sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). Discriminative accuracy was examined by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 97 332 evaluated patients, 1714 (1.8%) experienced the primary outcome. The qSOFA ≥2 was less sensitive (11.7% (95% CI: 10.2% to 13.3%) vs 25.1% (95% CI: 23.1% to 27.3%)) and more specific (99.3% (95% CI: 99.2% to 99.3%) vs 97.5% (95% CI: 97.4% to 97.6%)) than EWS ≥5. The NPV was similar for the two scores (EWS ≥5, 98.6% (95% CI: 98.6% to 98.7%) and qSOFA ≥2, 98.4% (95% CI: 98.3% to 98.5%)), while the PPV was 15.1% (95% CI: 13.8% to 16.5%) for EWS ≥5 and 22.4% (95% CI: 19.7% to 25.3%) for qSOFA ≥2. The AUROC was 0.72 (95% CI: 0.70 to 0.73) for EWS and 0.66 (95% CI: 0.65 to 0.67) for qSOFA. CONCLUSION: The qSOFA was less sensitive (qSOFA ≥2 vs EWS ≥5) and discriminatively accurate than the EWS for predicting ICU admission and/or death within 2 days after an initial EWS. This study did not support replacing EWS with qSOFA in all hospitalised patients.

Is the risk of cardiovascular disease increased in living kidney donors? A Danish population-based cohort study.

Reduced renal function is associated with cardiovascular disease (CVD); however, how living donor nephrectomy affects the risk of CVD remains controversial. We conducted a nationwide cohort study including living kidney donors in Denmark from 1996 to 2018 to assess the risk of hypertension, atrial fibrillation/flutter (AF), major adverse cardiovascular events (MACE; composite of myocardial infarction, ischemic stroke, and death) and death after living kidney donation. As comparisons we identified: a cohort of healthy individuals from the general population and an external blood donor cohort. We followed kidney donors (1,103 when compared with the general population cohort; 1,007 when compared with blood donors) for a median of 8 years. Kidney donors had an increased risk of initiating treatment for hypertension when compared with blood donors (standardized incidence ratio [SIR], 1.40; 95% confidence interval [CI], 1.17-1.66) but they did not have increased risk of MACE neither when compared with the general population cohort (hazard ratio, 0.68; 95% CI, 0.52-0.89) nor with blood donors (SIR, 1.17; 95% CI, 0.88-1.55). Neither did they have increased risks of AF and death. Thus, living kidney donation may be associated with increased risk of hypertension; however, we did not identify increased risks of CVD or death.

Risk factors of hospitalisation for thrombosis in adults with primary immune thrombocytopenia, including disease-specific treatments: a French nationwide cohort study.

We aimed to assess the risk factors of venous thrombosis (VT) and arterial thrombosis (AT) in adults with primary immune thrombocytopenia (ITP), particularly in relation to treatments. The population comprised all incident primary ITP adults in France between 2009 and 2017 (FAITH cohort; NCT03429660) built in the national health database. Outcomes were the first hospitalisation for VT and AT. Multivariable Cox regression models included baseline risk factors, time-varying exposure to ITP drugs, splenectomy and to cardiovascular drugs. The cohort included 10 039 patients. A higher risk of hospitalisation for VT was observed with older age, history of VT, history of cancer, splenectomy [hazard ratio (HR) 3·23, 95% confidence interval (CI) 2·26-4·61], exposure to corticosteroids (HR 3·55, 95% CI 2·74-4·58), thrombopoietin-receptor agonists (TPO-RAs; HR 2·28, 95% CI 1·59-3·26) and intravenous immunoglobulin (IVIg; HR 2·10, 95% CI 1·43-3·06). A higher risk of hospitalisation for AT was observed with older age, male sex, a history of cardiovascular disease, splenectomy (HR 1·50, 95% CI 1·12-2·03), exposure to IVIg (HR 1·85, 95% CI 1·36-2·52) and TPO-RAs (HR 1·64, 95% CI 1·26-2·13). Rituximab was not associated with an increased risk. These findings help to estimate the risk of thrombosis in adult patients with ITP and to select treatment.

Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model.

OBJECTIVES: Serious infection is a concern for patients with inflammatory joint diseases treated with biological drugs (bDMARDs). The objectives were to compare risk of serious infection, defined as infection leading to hospitalization, in patients initiating bDMARD treatment with that in the general population and, second, to develop a simple clinical prediction model and to obtain risk estimates for individual patients. METHODS: This was a matched-cohort study based on nationwide registries in Denmark. Patients with RA, axial SpA and PsA initiating first bDMARD monitored in the DANBIO registry were matched 1:10 by age, gender and postal code with controls from the general population. The risk of serious infection during 12 months' follow-up was assessed with Cox regression. Prediction models were developed using logistic regression and compared using area under the receiver operating characteristic curve (AUC). RESULTS: We included 11 372 patients and 113 715 controls. During follow-up, 522 patients (4.6%) and 1434 controls (1.3%) developed a serious infection (hazard ratio 3.7, 95% CI 3.4, 4.1). Age-stratified risk was largely similar across diagnoses. A simple prediction model, the 'DANBIO infection risk score', based on age and a count of six clinical risk factors had moderate discriminative power (internal validation: AUC 0.69) that was comparable to that of the existing RABBIT (Rheumatoide Arthritis Beobachtung der BIologika-Therapie) Risk Score (external validation: AUC 0.68). CONCLUSION: Patients with inflammatory joint diseases initiating bDMARD treatment had a four times increased risk of serious infection compared with the general population. A simple prediction model, feasible for shared decision-making, was developed to obtain risk estimates for individual patients.

Predictors for and outcomes after bone marrow biopsy in Scandinavian patients with chronic immune thrombocytopenia.

OBJECTIVES: To examine predictors for bone marrow biopsy (BMB) and the outcome following BMB in patients with chronic immune thrombocytopenia (cITP). METHODS: We identified patients diagnosed with cITP during 2009-2017 and obtained information on BMB, cITP treatment and subsequent thrombotic events, hospitalized bleeding, hematological cancer, and death using data from population-based healthcare databases and medical records in Denmark, Norway, and Sweden. RESULTS: Among 4471 adults (≥18 years) with cITP, 1683 (37.6%) underwent BMB before cITP diagnosis, while cumulative BMB incidence after cITP diagnosis date was 3.1% at 1 year and 7.5% at 5 years. Predictors of having a BMB after cITP diagnosis included older age, male sex, low baseline platelet count, splenectomy, and number of cITP treatments. Compared with patients without BMB, patients with BMB had higher rates of thrombotic events (1 year adjusted hazard ratio [HR] 1.53 [95% CI, 0.92-2.54]), hospitalized bleeding episodes (1 year adjusted HR 1.72 [95% CI, 1.15-2.58]), hematological cancer (1 year adjusted HR 35.26 [95% CI 17.67-70.34]), and all-cause mortality (1 year adjusted HR 1.97 [95% CI, 1.44-2.68]). CONCLUSION: Patients who undergo BMB after cITP diagnosis represent a subset of patients with more severe disease and increased rates of complications as well as hematological malignancies.

Urinary tract infections and risk of squamous cell carcinoma bladder cancer: A Danish nationwide case-control study.

Schistosoma haematobium infection can lead to squamous cell carcinomas (SCC) of the bladder. Whether this also applies to more common urinary tract infections (UTIs) is unclear. We therefore aimed to investigate the association between UTIs, reflected by the use of specific antibiotics and risk of SCC of the bladder. We conducted a Danish nationwide case-control study and identified histologically verified bladder cancer cases (2000-2015; n = 12,271) and age- and sex-matched cancer-free controls. We computed odds ratios (ORs) with 95% confidence intervals (CI) associating the use of UTI-specific antibiotics with SCC bladder cancer, using conditional logistic regression. We applied a 2-year lag-time to minimize reverse causation. To aid interpretation, similar analyses were performed for other bladder cancer types and other antibiotics. We identified 333 SCC cases (2.7% of all bladder cancers). Compared to no use (0-1 prescription), high-use (≥10 prescriptions) of UTI-specific antibiotics was associated with SCC with an OR of 11.4 (CI 7.6-17.2) and a clear dose-response pattern (ptrend < 0.001). Use of phenoxymethylpenicillin, an antibiotic not used against UTIs, was not associated with SCC after adjustment for use of UTI-specific antibiotics (OR 0.5). Furthermore, UTI-specific antibiotic use was not associated with urothelial carcinomas (n = 11,029; OR 1.13; CI 0.97-1.32). Excluding patients with known urogenital disease did not influence the SCC estimates (overall OR 10.8; CI 6.2-18.9). Data on smoking were lacking, however, a quantitative bias analysis suggested this to be of limited importance. In conclusion, common UTIs are strong, dose-dependent and specifically associated with risk of SCC of the bladder.