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Background Chronic kidney disease (CKD) is a growing global health concern. Identifying individuals in routine clinical care with new-onset CKD at high risk of rapid progression of the disease is imperative to guide allocation of prophylactic interventions, but community-based data are limited. We aimed to examine the risk of rapid progression, kidney failure, hospitalization and death among adults with incident CKD stage G3 and to clarify the association between predefined risk markers and rapid CKD progression. Methods Using plasma creatinine measurements for the entire Danish population from both hospitals and primary care, we conducted a nationwide, population-based cohort study, including adults in Denmark with incident CKD stage G3 in 2017–2020. We estimated 3-year risks of rapid progression (defined by a confirmed decline in estimated glomerular filtration rate of ≥5 mL/min/1.73 m2/year), kidney failure, all-cause hospitalization and death. To examine risk markers, we constructed a heat map showing the risk of rapid progression based on predefined markers: albuminuria, sex, diabetes and hypertension/cardiovascular disease. Results Among 133 443 individuals with incident CKD stage G3, the 3-year risk of rapid progression was 14.6% [95% confidence interval (CI) 14.4–14.8]. The 3-year risks of kidney failure, hospitalization and death were 0.3% (95% CI 0.3–0.4), 53.3% (95% CI 53.0–53.6) and 18.1% (95% CI 17.9–18.4), respectively. In the heat map, the 3-year risk of rapid progression ranged from 7% in females without albuminuria, hypertension/cardiovascular disease or diabetes, to 46%–47% in males and females with severe albuminuria, diabetes and hypertension/cardiovascular disease. Conclusion This population-based study shows that CKD stage G3 is associated with considerable morbidity in a community-based setting and underscores the need for optimized prophylactic interventions among such patients. Moreover, our data highlight the potential of using easily accessible markers in routine clinical care to identify individuals who are at high risk of rapid progression. [ABSTRACT FROM AUTHOR]

Objective: Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death.Research Design and Methods: We linked data from two Danish type 2 diabetes cohorts, the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) and the Danish Centre for Strategic Research in Type 2 Diabetes (DD2), to national health care registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios (IRRs) of CVD and all-cause mortality comparing MNSIq scores ≥4 with scores <4. Analyses were adjusted for a range of established CVD risk factors.Results: In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores <4, MNSIq scores ≥4 were associated with higher incidence rate of CVD, with IRRs of 1.79 (95% CI 1.38-2.31) in ADDITION-Denmark, 1.57 (CI 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥4 did not associate with mortality; combined mortality rate ratio was 1.11 (CI 0.83-1.48).Conclusions: The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes with a high incidence rate of subsequent CVD. MNSIq scores ≥4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors. [ABSTRACT FROM AUTHOR]

Background: Individuals with type 2 diabetes (T2D) have a twofold increased risk for cardiovascular events (CVE), and CVE is responsible for nearly 80% of the mortality. Current treatment guidelines state that individuals should immediately initiate antidiabetic treatment and cardiovascular risk-factor management from T2D diagnosis. However, the evidence base is sparse, and randomized trials are unlikely to be conducted. We examined the impact of being eligible for T2D treatment, as determined by the threshold of HbA1c ≥ 6.5% (≥ 48 mmol/mol), on all-cause mortality and CVE. We hypothesised that individuals who were just above this threshold had a lower risk of CVE and all-cause mortality than individuals just below. Methods and Findings: We used the regression discontinuity design (RDD), a quasi-experimental design, comparing rates of all-cause mortality and CVE in people just below and just above the eligibility for treatment threshold. We included Danish healthcare records from 43,070 individuals aged 40– 80 years with no previous T2D record and the first record of HbA1c in the range of 6.0– 7.0% (42– 53 mmol/mol) between 2006 and 2014. In total, 36,360 individuals had the first record of HbA1c between 6.0% and 6.4% (42– 47 mmol/mol), and 6710 individuals had a first record between 6.5% and 7.0% (48– 53 mmol/mol). Individuals with a measurement just above 6.5% (48 mmol/mol) had a 21% lower rate of death or CVE, compared to those just below (hazard ratio: 0.79 (95% CI 0.69– 0.90)). Few individuals received early metformin treatment. However, the chance of metformin treatment initiation within 3 months was substantially higher for individuals with an HbA1c measurement above (14%) than below (1%) the threshold. Conclusion: Individuals with first record of HbA1c measure just above treatment threshold experienced a 21% lower rate of death or CVE than those just below. Lifestyle modifications and cardiovascular risk-factor management may contribute to this reduced rate. [ABSTRACT FROM AUTHOR]

Background: Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods: This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results: Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion: In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use. [ABSTRACT FROM AUTHOR]

Background: Latent Autoimmune Diabetes in Adults (LADA) is the second most common form of diabetes, but data on its clinical course and prognosis are scarce. We compared long-term risk of mortality and cardiovascular outcomes in patients with LADA, type 2 diabetes mellitus (T2D), and insulin deficient diabetes (IDD).Methods: We conducted a cohort study of 4368 adults with diabetes referred to the Department of Endocrinology, Odense University Hospital, Denmark, between 1997 and 2012. Data on comorbidity, cardiovascular outcomes and death were obtained from prospective medical databases. We compared adjusted hazard ratios (HRs) of mortality and cardiovascular outcomes for patients with LADA, T2D and IDD, respectively.Results: We included 327 patients with LADA, 3539 with T2D and 502 with IDD. At diagnosis, patients with LADA were older (50 years (IQR 37-59)) than IDD patients (40 years (IQR 28-52)), but younger than patients with T2D (55 years (IQR 45-64)). During a median follow-up period of 6.6 years (IQR 3.4-9.4), patients with IDD had higher mortality than patients with LADA, age- and gender-adjusted HR 2.2 (95% CI, 1.5-3.2). T2D also conferred higher mortality than LADA, HR 1.4 (95% CI, 1.0-1.9). Compared with LADA patients, cardiovascular outcome rates were increased both with IDD, HR 1.2 (95% CI, 0.7-2.0) and T2D, HR 1.2 (95% CI, 0.8-1.8), with the strongest association observed for T2D vs. LADA and acute myocardial infarction HR 1.7 (95% CI, 0.8-3.5).Conclusion: LADA seems to be associated with lower mortality and lower risk of cardiovascular events, compared with both T2D and IDD. [ABSTRACT FROM AUTHOR]

Background: To reduce the increasing burden of pneumonia hospitalizations, we need to understand their determinants. Being married may decrease the risk of severe infections, due to better social support and healthier lifestyle. Patients and methods: In this population-based case-control study, we identified all adult patients with a first-time pneumonia-related hospitalization between 1994 and 2008 in Northern Denmark. For each case, ten sex- and age-matched population controls were selected from Denmark's Civil Registration System. We performed conditional logistic regression analysis to estimate the odds ratios (ORs) for pneumonia hospitalization among persons who were divorced, widowed, or never married, as compared with married persons, adjusting for age, sex, 19 different comorbidities, alcoholism-related conditions, immunosuppressant use, urbanization, and living with small children. Results: The study included 67,162 patients with a pneumonia-related hospitalization and 671,620 matched population controls. Compared with controls, the pneumonia patients were more likely to be divorced (10% versus 7%) or never married (13% versus 11%). Divorced and never-married patients were much more likely to have previous diagnoses of alcoholism-related conditions (18% and 11%, respectively) compared with married (3%) and widowed (6%) patients. The adjusted OR for pneumonia-related hospitalization was increased, at 1.29 (95% confidence interval [CI]: 1.25-1.33) among divorced; 1.15 (95% CI: 1.12-1.17) among widowed; and 1.33 (95% CI: 1.29-1.37) among never-married individuals as compared with those who were married. Conclusion: Married individuals have a decreased risk of being hospitalized with pneumonia compared with never-married, divorced, and widowed patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The extent and magnitude of mortality risk among patients splenectomised for a variety of indications is not well-described in the literature. We assessed mortality risk among splenectomised patients compared to the general population and to un-splenectomised patients with similar underlying medical conditions. Methods: We conducted a historical population-based cohort study in Denmark between January 1, 1996 and December 31, 2005. Mortality risk was evaluated within 90days, 91–365days, and >365days post-splenectomy, controlling for age, sex, and comorbid conditions using Cox proportional hazards models for a splenectomised cohort compared to the general Danish population and a matched indication cohort. Results: We identified a total of 3812 splenectomised patients, 38,120 population comparisons, and 8310 matched indication comparisons. Within 90days post-splenectomy, the adjusted relative risk (RR) for death, regardless of indication, was highly elevated compared to the general population: RR 33.6 [95% confidence interval (CI): 6.9, 35.0]. This risk declined substantially after 90days post-splenectomy but remained higher 365days post-splenectomy for all indications compared to the general population. When compared to the matched indication cohort, short- and long-term mortality risk with splenectomy was not increased. Conclusion: Regardless of indication, the adjusted short- and long-term risk of death for splenectomised patients was higher than the general population. Most of this risk seems to be due to the underlying splenectomy indication and not to splenectomy alone. [Copyright &y& Elsevier]

Objective. Use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of upper gastrointestinal bleeding and this risk is amplified by concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs). The aim of the study was to examine the impact of SSRI use alone or in combination with NSAIDs on 30-day mortality after peptic ulcer bleeding (PUB). Material and methods. A population-based cohort study of patients with a first hospitalization with PUB in three Danish counties was carried out between 1991 and 2005 using medical databases. We calculated 30-day mortality rate ratios (MRRs) associated with the use of SSRIs, alone or in combination with NSAIDs, adjusted for important covariates. Results. Of 7415 patients admitted with PUB, 5.9% used SSRIs only, and 3.8% used SSRIs in combination with NSAIDs, with a 30-day mortality of 11.8% and 11.3%, respectively. Compared with patients who used neither SSRIs nor NSAIDs, the adjusted 30-day MRR was 1.02 (95% CI: 0.76--1.36) for current users of SSRIs and 0.89 (0.62--1.28) for the combined use of SSRIs with NSAIDs. There was a 2.11-fold (95% CI 1.35--3.30) increased risk of death associated with SSRI use starting within 60 days of admission; for those younger than 80 years, the adjusted MRR was 1.54 (0.72--3.29), and 2.57 (1.47--4.49) for those older than 80 years. Conclusions. Use of SSRIs, alone or in combination with NSAIDs, was not associated with increased 30-day mortality following PUB. However, increased mortality was found in patients who started SSRI therapy, particularly among those older than 80 years. We can only speculate on whether this finding is due to pharmacological action or confounding factors. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from invasive pneumococcal disease (IPD). Methods and Findings: In a nationwide population-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality as compared with serotype 1 (all: adjusted odds ratio ≥3, p<0.001). In children younger than 5 y, associations between serotypes and mortality were different than in adults but statistical precision was limited because of low overall childhood-related mortality. Conclusions: Specific pneumococcal serotypes strongly and independently affect IPD associated mortality. [ABSTRACT FROM AUTHOR]

The article presents an analysis of the effect of statins after hospitalization of patients with pneumonia. The study explores whether preadmission statin use decreased risk of death, bacteremia and pulmonary complications after pneumonia. Of the 29,900 patients with pneumonia, 1,371 or 4.6% were current statin users and mortality among them was lower than among nonusers, 10.3% against 15.7% after 30 days and 16.8% versus 22.4% after 90 days. This shows that the use of statins is linked with decreased mortality after hospitalization with pneumonia.

Background: There are limited data describing how pre-existing heart failure affects mortality following pneumonia.Objective: To examine the association between history and severity of heart failure and mortality among patients hospitalized for pneumonia.Design: Population-based cohort study in Western Denmark between 1994 and 2003.Patients: 33,736 adults with a first-time hospitalization for pneumonia. Heart failure was identified and categorized based on data linked from population-based health care databases.Measurements: We compared 30-day mortality between patients with pre-existing heart failure and other pneumonia patients, while adjusting for age, gender, comorbidity, and medication use.Results: The 30-day mortality was 24.4% among heart-failure patients and 14.4% among other patients, with an adjusted 30-day mortality rate ratio (MRR) of 1.40 (95% CI: 1.29-1.51). Adjusted MRRs increased according to severity of pre-existing heart failure, as indicated by medication regimen: thiazide-based, MRR = 1.09 (95% CI: 0.79-1.50); loop-diuretics, MRR = 1.25 (95% CI: 1.10-1.43); loop-diuretics and digoxin, MRR = 1.35 (95% CI: 1.18-1.55); loop-diuretics and spironolactone, MRR = 1.72 (95% CI: 1.49-2.00). Pre-existing heart valve disease and atrial fibrillation substantially increased mortality.Conclusion: History and severity of heart failure are associated with a poor outcome for patients hospitalized with pneumonia. [ABSTRACT FROM AUTHOR]

The article studies the association between chronic obstructive pulmonary disease (COPD) and 30-day mortality among patients with bleeding and perforated peptic ulcer. It includes an in-depth analysis of the correlation between COPD and the increased risk for peptic ulcer. Research findings show that short-term mortality in substantially increased by COPD in patients with perforated peptic ulcers and bleeding.

What is already known about this subject • Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high-risk patients. • Pain management guidelines propose tramadol as a treatment option for mild-to-moderate pain in patients at high risk of gastrointestinal side-effects, including peptic ulcer disease. • Tramadol may mask symptoms of peptic ulcer complications, yet tramadol's effect on peptic ulcer prognosis is unknown. What this study adds • In this population-based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs. • Among users of tramadol, alone or in combination with NSAIDs, adjusted 30-day mortality rate ratios were 2.02 [95% confidence interval (CI) 1.17, 3.48] and 1.32 (95% CI 0.89, 1.95), compared with patients who used neither tramadol nor NSAIDs. Aim Use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk and worsens prognosis for patients with complicated peptic ulcer disease. Therefore, patients who are at high risk of peptic ulcer often use tramadol instead of NSAIDs. Tramadol's effect on peptic ulcer prognosis is unknown. The aim was to examine mortality in the 30 days following hospitalization for perforated peptic ulcer among tramadol and NSAID users compared with non-users. Methods The study was based on data on reimbursed prescriptions and hospital discharge diagnoses for the 1993–2004 period, extracted from population-based healthcare databases. All patients with a first-time diagnosis of perforated peptic ulcer were identified, excluding those with previous ulcer diagnoses or antiulcer drug use. Cox regression was used to estimate 30-day mortality rate ratios for tramadol and NSAID users compared with non-users, adjusting for use of other drugs and comorbidity. Results Of 1271 patients with perforated peptic ulcers included in the study, 2.4% used tramadol only, 38.9% used NSAIDs and 7.9% used both. Thirty-day mortality was 28.7% overall and 48.4% among users of tramadol alone. Compared with the 645 patients who used neither tramadol nor NSAIDs, the adjusted mortality rate in the 30 days following hospitalization was 2.02-fold [95% confidence interval (CI) 1.17, 3.48] higher for the 31 ‘tramadol only’ users, 1.41-fold (95% CI 1.12, 1.78) higher for the 495 NSAID users and 1.32-fold (95% CI 0.89, 1.95) higher for the 100 patients who used both drugs. Conclusion Among patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs. [ABSTRACT FROM AUTHOR]

Background: Mortality after perforated and bleeding peptic ulcer increases with age. Limited data exist on how the higher burden of comorbidity among elderly patients affects this association. We aimed to examine the association of age with short-term mortality after perforated and bleeding peptic ulcer and to determine the impact of comorbidity on this association. Methods: In this population-based cohort study in three Danish counties between 1991 and 2003 we identified two cohorts of patients: those hospitalized with a first-time discharge diagnosis of perforated peptic ulcer and those with bleeding peptic ulcer. The diagnoses were ascertained from hospital discharge registries and mortality through the Danish Civil Registration System. Information on comorbidity and use of ulcer-related drugs was obtained through administrative medical databases. We computed age-, gender- and comorbidity-standardized 30-day mortality rates and used Cox's regression to estimate adjusted 30-day mortality rate ratios (MRR) for elderly compared with younger patients. Results: Among 2,061 patients with perforated peptic ulcer, 743 (36%) were 65-79 years old and 513 patients (25%) were aged 80+ years. Standardized 30-day mortality was 8.9% among patients younger than 65 years rising to 44.6% among patients aged 80+ years, corresponding to an adjusted MRR of 5.3 (95% CI: 4.0-7.0). Among 7,232 patients with bleeding peptic ulcer 2,372 (33%) were aged 80+ years. Standardized 30-day mortality among patients younger than 65 was 4.3% compared with 16.9% among patients aged 80+ years, corresponding to an adjusted MRR of 3.7 (95% CI: 2.9-4.7). Analyses stratified by comorbidity consistently showed high MRRs among elderly patients, regardless of comorbidity level. Conclusion: Ageing is a strong predictor for a poor outcome after perforated and bleeding peptic ulcer independently of comorbidity. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Diabetes may influence the outcome of complicated peptic ulcer disease, due to angiopathy, blurring of symptoms, and increased risk of sepsis. We examined whether diabetes increased 30-day mortality among Danish patients hospitalized with bleeding or perforated peptic ulcers. RESEARCH DESIGN AND METHODS -- This population-based cohort study took place in the three Danish counties of North Jutland, Viborg, and Aarhus between 1991 and 2003. Patients hospitalized with a first-time diagnosis of peptic ulcer bleeding or perforation were identified using the counties' hospital discharge registries. Data on diabetes, other comorbidities, and use of ulcer-associated drugs were obtained from discharge registries and prescription databases. The Danish Civil Registry System allowed complete follow-up for mortality. The outcome under study was 30-day mortality in diabetic versus nondiabetic patients, adjusted for potential confounders. RESULTS -- We identified 7,232 patients hospitalized for bleeding ulcers, of whom 731 (10.1%) had diabetes. The 30-day mortality among diabetic patients was 16.6 vs. 10.1% for other patients with bleeding ulcers. The adjusted 30-day mortality rate ratio (MRR) for diabetic patients was 1.40 (95% CI 1.15-1.70). We also identified 2,061 patients with perforated ulcers, of whom 140 (6.8%) had diabetes. The 30-day mortality among diabetic patients was 42.9 vs. 24.0% in other patients with perforated ulcers, corresponding to an adjusted 30-day MRR of 1.51 (1.15-1.98). CONCLUSIONS -- Among patients with peptic ulcer bleeding and perforation, diabetes appears to be associated with substantially increased short-term mortality. [ABSTRACT FROM AUTHOR]