Hypoparathyroidism and mortality after total thyroidectomy: A nationwide matched cohort study.

OBJECTIVE: Total thyroidectomy (TT) carries a risk of hypoparathyroidism (hypoPT). Recently, hypoPT has been associated with higher overall mortality rates. We aimed to evaluate the frequency of hypoPT and mortality in patients undergoing TT in Denmark covering 20 years. DESIGN: Retrospective Cohort study. PATIENTS AND MEASUREMENTS: Using population-based registries, we identified all Danish individuals who had undergone TT between January 1998 and December 2017. We included a comparison cohort by randomly selecting 10 citizens for each patient, matched on sex and birth year. HypoPT was defined as treatment with active vitamin D after 12 months postoperatively. We used cumulative incidence to calculate risks and Cox regression to compare the rate of mortality between patients and the comparison cohort. We evaluated patients in different comorbidity groups using the Charlson Comorbidity Index and by different indications for surgery. RESULTS: 7912 patients underwent TT in the period. The prevalence of hypoPT in the study period was 16.6%, 12 months postoperatively. After adjusting for potential confounders the risk of death due to any causes (hazard ratio; 95% confidence intervals) following TT was significantly increased (1.34; 1.15-1.56) for patients who developed hypoPT. However, subgroup analysis revealed mortality was only increased in malignancy cases (2.48; 1.99-3.10) whereas mortality was not increased when surgery was due to benign indications such as goitre (0.88; 0.68-1.15) or thyrotoxicosis (0.86; 0.57-1.28). CONCLUSIONS: The use of active vitamin D for hypoPT was prevalent one year after TT. Patients with hypoPT did not have an increased risk of mortality following TT unless the indication was due to malignancy.

Regional variation in incidence and prognosis of acute kidney injury.

BACKGROUND: Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up, and prognosis of AKI in Denmark. METHODS: Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up, and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function. RESULTS: We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1 000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up, and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories. CONCLUSIONS: Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up, and nephrology follow-up after AKI varied across regions and municipality categories.

Risk of infections and mortality in Danish patients with cancer diagnosed with bone metastases: a population-based cohort study.

OBJECTIVES: Risk of infections in patients with solid cancers and bone metastases (BM) and the subsequent impact on prognosis is unclear. We examined the risk of infections among patients with cancer diagnosed with BM and the subsequent impact of infections on mortality. DESIGN: Population-based cohort study. SETTING: Danish medical databases holding information on all hospital contacts in Denmark. PARTICIPANTS: Adult patients with solid cancers and BM between 1 January 1994 and 30 November 2013. OUTCOME MEASURES: In the risk analyses, the outcome was time to hospitalisation for common severe infections, pneumonia, sepsis and urinary tract infections. In the mortality analysis, we used Cox regression to compute HRs of death, modelling infection as time-varying exposure, stratifying for primary cancer type and adjusting for age, sex and comorbidities. RESULTS: Among 23 336 patients with cancer and BM, cumulative incidences of common severe infections were 4.6%, 14.0% and 20.0% during 1 month, 1 year and 10 years follow-up. The highest incidence was observed for pneumonia, followed by urinary tract infections and sepsis. Infection was a strong predictor of 1 month mortality (adjusted HR: 2.1 (95% CI 1.8 to 2.3)) and HRs increased after 1 and 10 years: 2.4 (95% CI 2.3 to 2.6) and 2.4 (95% CI 2.4 to 2.6). Sepsis and pneumonia were the strongest predictors of death. Results were consistent across cancer types. CONCLUSION: Patients with cancer and BM were at high risk of infections, which was associated with a more than twofold increased risk of death for up to 10 years of follow-up. The findings underscore the importance of preventing infections in patients with cancer and BM.

Incidence of von Willebrand disease in Denmark, 1995-2016: A cohort study.

INTRODUCTION: Information about temporal development of von Willebrand disease (VWD) incidence at a population level is scarce. To our knowledge, no study has described the incidence of VWD at a population level. AIM: To estimate overall and annual incidence rates of hospital diagnosed VWD in Denmark between 1995 and 2016 as well as the frequency of hospital treated bleeding episodes before and after VWD diagnosis. METHODS: A registry-based cohort study that included all Danish patients with a first diagnosis of VWD in Denmark, identified in the Danish National Patient Registry through 1995-2016. RESULTS: We identified 1,035 patients with a diagnosis of VWD. The overall incidence rate of VWD in 1995-2016 was 8.6 (95% CI: 8.1-9.2). The annual age-standardized incidence rate per 100 000 person-years varied between 4.1 (95% CI: 2.4-5.9) in 1998 and 16.7 (95% CI: 13.1-20.3) in 2005. A prominent peak in rates appeared from 2002 to 2008. One and five years before VWD diagnosis, 6% and 11.5% of the patients had at least one hospital treated bleeding episode. One and five years after diagnosis, the corresponding percentages were 7.9% and 13.4%. CONCLUSION: These results are the first population-based estimates of VWD incidence. The incidence may be underestimated because asymptomatic individuals may not be diagnosed. The observed peak in incidence from 2002-2008 may be explained by increased medical attention, leading to more patients being diagnosed, rather than an actual increase in VWD incidence. However, overall, we observed no systematic changes in VWD incidence over the study period.

Occurrence, mortality and cost of brain disorders in Denmark: a population-based cohort study.

OBJECTIVES: To examine the occurrence of brain disorders (ie, neurological and mental disorders) in Denmark and mortality and cost of illness among affected persons. DESIGN: Matched cohort study. SETTING: We obtained routinely collected registry data on all Danish residents during 1995-2015. PARTICIPANTS: We identified all persons alive on 1 January 2015 with a diagnosis of 25 specific brain disorders (prevalent cohort) and all persons with an incident diagnosis during 2011-2015 (incident cohort). Each person was matched on age and sex with 10 persons from the general population without the brain disorder of interest. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence and incidence of hospital-diagnosed brain disorders, 1-year absolute and relative mortality, and attributable direct and indirect costs of illness compared with the corresponding matched cohorts. RESULTS: We identified 1 075 081 persons with at least one prevalent brain disorder (any brain disorder) on 1 January 2015, corresponding to 18.9% of the Danish population. The incidence rate of any brain disorder during 2011-2015 was 1349 per 100 000 person-years (95% CI 1345 to 1353). One-year mortality after diagnosis was increased in persons with any brain disorder (HR 4.7, 95% CI 4.7 to 4.8) and in persons in every group of specific brain disorders compared with the matched cohort from the general population. The total attributable direct costs of brain disorders in 2015 were €5.2 billion and total attributable indirect costs were €11.2 billion. Traumatic brain injury, stress-related disorders, depression and stroke were the most common brain disorders. Attributable costs were highest for depression, dementia, stress-related disorders and stroke. CONCLUSIONS: One in five Danish residents alive on 1 January 2015 had been diagnosed with at least one brain disorder, and mortality was five times higher in persons with any diagnosed brain disorder than in the general population. We found high attributable direct and indirect costs of brain disorders.

The Association Between Rhabdomyolysis, Acute Kidney Injury, Renal Replacement Therapy, and Mortality.

BACKGROUND: We examined the association between creatine phosphokinase level in rhabdomyolysis patients and risk of acute kidney injury, renal replacement therapy, and death within 30 days. METHODS: The cohort included patients admitted with rhabdomyolysis from November 1, 2011 to March 1, 2014. Rhabdomyolysis was defined as a creatine phosphokinase level higher than 1000 U/L. Information on laboratory variables was obtained from a laboratory database. Medical data were obtained from registries. Acute kidney injury was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The 30-day risk of outcomes was estimated using the cumulative incidence method. Spline regression applied to imputed datasets with adjustment for baseline variables was used to assess the appropriateness of the categorization chosen for creatine phosphokinase (1000-5000 U/L, 5001-15,000 U/L, and 15,000+ U/L). RESULTS: The study included 1027 patients (58.2% male) with a median age of 73.5 years. The median creatine phosphokinase level at rhabdomyolysis diagnosis was 2257 U/L (interquartile range=1404-3961 U/L). The 30-day risks of acute kidney injury according to the three creatinine phosphokinase levels were 42% (95% CI=38-45%), 44% (95% CI=36-52%), and 74% (95% CI=57-85%), respectively, and the risks of renal replacement therapy for the three levels were 3% (95% CI=2-5%), 4% (95% CI=2-7%), and 11% (3-23%), respectively. The 30-day risk of death was 17% (95% CI=14-20%), 16% (95% CI=11-22%), and 11% (95% CI=3-23%), respectively. With increasing creatine phosphokinase levels, the spline plots supported the increasing risk of acute kidney injury and renal replacement therapy, as well as a decreasing risk of death. However, the risk estimates for renal replacement therapy and death were imprecise. CONCLUSION: Elevated initial creatine phosphokinase values were associated with an increased risk of acute kidney injury, while estimates of the risk of renal replacement therapy and death were imprecise.

Renin-Angiotensin System Blockers and Adverse Outcomes of Influenza and Pneumonia: A Danish Cohort Study.

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.

Cardiovascular Outcomes and All-cause Mortality Following Measurement of Endogenous Testosterone Levels.

Although reduced testosterone levels are common in aging populations, the clinical consequences remain to be further explored. We examined whether low total testosterone levels are associated with stroke (ischemic and hemorrhagic), myocardial infarction (MI), venous thromboembolism (VTE), and all-cause mortality in adult men. We conducted a cohort study in the Central Denmark Region (2000 to 2015). We included all men with a first-ever laboratory testosterone result and computed the 5-year risks of cardiovascular outcomes and all-cause mortality. Propensity score-weighted hazard ratios were computed, comparing persons with normal versus low testosterone levels. Individuals were censored at testosterone treatment during follow-up (3%). We identified 4,771 men with low testosterone levels and 13,467 with normal levels. Persons with low testosterone levels were older (median ages, 55 years vs 50 years) and had more co-morbidities than men with normal testosterone levels. Persons with low testosterone had higher 5-year risks of stroke (2.4% vs 1.5%), MI (1.5% vs 1.2%), VTE (1.4% vs 0.9%), and all-cause mortality (17.8% vs 6.8%) than persons with normal testosterone levels. After propensity score-weighting, the associations with cardiovascular outcomes reached unity. The 5-year hazard ratios were 1.14 (95% confidence intervals [CIs] 0.87 to 1.49) for stroke, 0.95 (95% CI 0.70 to 1.30) for MI, 1.10 (95% CI 0.78 to 1.55) for VTE, whereas it was 1.48 (95% CI 1.32 to 1.64) for all-cause mortality. In conclusion, low testosterone level was a strong predictor for cardiovascular outcomes and all-cause mortality in unadjusted models, however only the association between low testosterone and all-cause mortality persisted after adjustment for age and co-morbidity.

Benchmarking Danish hospitals on mortality and readmission rates after cardiovascular admission.

OBJECTIVE: The aim of this study was to examine hospital performance measures that account more comprehensively for unique mixes of patients' characteristics. DESIGN: Nationwide cohort registry-based study within a population-based health care system. PARTICIPANTS: In this study, 331,513 patients discharged with a primary cardiovascular diagnosis from 1 of 26 Danish hospitals during 2011-2015 were included. Data covering all Danish hospitals were drawn from the Danish National Patient Registry and the Danish National Health Service Prescription Database. MAIN OUTCOME MEASURES: Thirty-day post-admission mortality rates, 30-day post-discharge readmission rates, and the associated numbers needed to harm were measured. METHODS: For each index hospital, we used a non-parametric logistic regression model to compute propensity scores. Propensity score weighted patients treated at other hospitals collectively resembled patients treated at the index hospital in terms of age, sex, primary discharge diagnosis, diagnosis history, medications, previous cardiac procedures, and comorbidities. Outcomes for the weighted patients treated at other hospitals formed benchmarks for the index hospital. Doubly robust regression formally tested whether the outcomes of patients at the index hospital differed from the outcomes of the patients used to form the benchmarks. For each index hospital, we computed the false discovery rate, ie, the probability of being incorrect if we claimed the hospital differed from its benchmark. RESULTS: Five hospitals exceeded their benchmark for 30-day mortality rates, with the number needed to harm ranging between 55 and 137. Seven hospitals exceeded their benchmark for readmission, with the number needed to harm ranging from 22 to 71. Our benchmarking approach flagged fewer hospitals as outliers compared with conventional regression methods. CONCLUSION: Conventional methods flag more hospitals as outliers than our benchmarking approach. Our benchmarking approach accounts more thoroughly for differences in hospitals' patient case mix, reducing the risk of false-positive selection of suspected outliers. A more comprehensive system of hospital performance measurement could be based on this approach.

Use of risk-adjusted CUSUM charts to monitor 30-day mortality in Danish hospitals.

BACKGROUND: Monitoring hospital outcomes and clinical processes as a measure of clinical performance is an integral part of modern health care. The risk-adjusted cumulative sum (CUSUM) chart is a frequently used sequential analysis technique that can be implemented to monitor a wide range of different types of outcomes. OBJECTIVE: The aim of this study was to describe how risk-adjusted CUSUM charts based on population-based nationwide medical registers were used to monitor 30-day mortality in Danish hospitals and to give an example on how alarms of increased hospital mortality from the charts can guide further in-depth analyses. MATERIALS AND METHODS: We used routinely collected administrative data from the Danish National Patient Registry and the Danish Civil Registration System to create risk-adjusted CUSUM charts. We monitored 30-day mortality after hospital admission with one of 77 selected diagnoses in 24 hospital units in Denmark in 2015. The charts were set to detect a 50% increase in 30-day mortality, and control limits were determined by simulations. RESULTS: Among 1,085,576 hospital admissions, 441,352 admissions had one of the 77 selected diagnoses as their primary diagnosis and were included in the risk-adjusted CUSUM charts. The charts yielded a total of eight alarms of increased mortality. The median of the hospitals' estimated average time to detect a 50% increase in 30-day mortality was 50 days (interquartile interval, 43;54). In the selected example of an alarm, descriptive analyses indicated performance problems with 30-day mortality following hip fracture surgery and diagnosis of chronic obstructive pulmonary disease. CONCLUSION: The presented implementation of risk-adjusted CUSUM charts can detect significant increases in 30-day mortality within 2 months, on average, in most Danish hospitals. Together with descriptive analyses, it was possible to use an alarm from a risk-adjusted CUSUM chart to identify potential performance problems.

Acute kidney injury treated with renal replacement therapy and 5-year mortality after myocardial infarction-related cardiogenic shock: a nationwide population-based cohort study.

BACKGROUND: Myocardial infarction-related cardiogenic shock is frequently complicated by acute kidney injury. We examined the influence of acute kidney injury treated with renal replacement therapy (AKI-RRT) on risk of chronic dialysis and mortality, and assessed the role of comorbidity in patients with cardiogenic shock. METHODS: In this Danish cohort study conducted during 2005-2012, we used population-based medical registries to identify patients diagnosed with first-time myocardial infarction-related cardiogenic shock and assessed their AKI-RRT status. We computed the in-hospital mortality risk and adjusted relative risk. For hospital survivors, we computed 5-year cumulative risk of chronic dialysis accounting for competing risk of death. Mortality after discharge was computed with use of Kaplan-Meier methods. We computed 5-year hazard ratios for chronic dialysis and death after discharge, comparing AKI-RRT with non-AKI-RRT patients using a propensity score-adjusted Cox regression model. RESULTS: We identified 5079 patients with cardiogenic shock, among whom 13% had AKI-RRT. The in-hospital mortality was 62% for AKI-RRT patients, and 36% for non-AKI-RRT patients. AKI-RRT remained associated with increased in-hospital mortality after adjustment for confounders (relative risk=1.70, 95% confidence interval (CI): 1.59-1.81). Among the 3059 hospital survivors, the 5-year risk of chronic dialysis was 11% (95% CI: 8-16%) for AKI-RRT patients, and 1% (95% CI: 0.5-1%) for non-AKI-RRT patients (adjusted hazard ratio: 15.9 (95% CI: 8.7-29.3). The 5-year mortality was 43% (95% CI: 37-53%) for AKI-RRT patients compared with 29% (95% CI: 29-31%) for non-AKI-RRT patients. The adjusted 5-year hazard ratio for death was 1.55 (95% CI: 1.22-1.96) for AKI-RRT patients compared with non-AKI-RRT patients. In patients with comorbidity, absolute mortality increased while relative impact of AKI-RRT on mortality decreased. CONCLUSION: AKI-RRT following myocardial infarction-related cardiogenic shock predicted elevated short-term mortality and long-term risk of chronic dialysis and mortality. The impact of AKI-RRT declined with increasing comorbidity suggesting that intensive treatment of AKI-RRT should be accompanied with optimized treatment of comorbidity when possible.