Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study.

In this nationwide register-based cohort study, we found no difference in the risk of fractures in patients discontinuing versus continuing alendronate (ALN) treatment after 5 years. INTRODUCTION: Information on fracture risk in patients discontinuing ALN in a real-life setting is sparse. We aimed to examine ALN discontinuation patterns, compare fracture rates in patients discontinuing versus continuing ALN after 5 years of treatment, and define determinants of fractures in ALN discontinuers. METHODS: A nationwide population-based cohort study using Danish health registry data. Our source population was individuals who had redeemed ≥ 2 ALN prescriptions between January 1, 1995, and September 1, 2017. RESULTS: We found that 25% of all ALN initiators used ALN for less than 1 year and 43% continued treatment for at least 5 years. We classified n = 1865 as ALN discontinuers and n = 29,619 as ALN continuers. Using Cox proportional hazards regression analysis and an "as-treated" approach, we observed no increased risk of any fracture (incidence rate ratio (IRR) 1.06, 95% CI 0.92-1.23), vertebral fracture (IRR 0.59, 95% CI 0.33-1.05), hip fracture (IRR 1.04, 95% CI 0.75-1.45), or major osteoporotic fracture (IRR 1.05, 95% CI 0.88-1.25) in the ALN discontinuers compared to continuers during a follow-up time of 1.84 ± 1.56 years (mean ± SD) and 2.51 ± 1.60 years, respectively. ALN re-initiation was a major determinant of follow-up among the discontinuers. Old age (> 80 vs. 50-60 years, unadjusted IRR 2.92, 95% CI 1.18-7.24) was the strongest determinant for fractures following ALN discontinuation. CONCLUSION: In a real-world setting, less than 50% continued ALN treatment for 5 years. We found no difference in the risk of fractures in patients discontinuing versus continuing ALN after 5 years.

Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Hospital-diagnosed overweight and obesity related to cancer risk: a 40-year Danish cohort study.

BACKGROUND: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. OBJECTIVES: To examine the overall cancer incidence and specific site-related cancer incidences among patients with overweight and obesity, compared to the general Danish population. METHODS: For this 40-year (1977-2016), nationwide, Danish cohort study, we reviewed medical databases to identify individuals with hospital-based overweight and obesity diagnoses. We computed age- and gender-standardized incidence ratios (SIRs) for subsequent cancer compared to the general population. RESULTS: We observed 20 706 cancers among 313 321 patients diagnosed with overweight and obesity (median age 43 years; median follow-up 6.7 years, range 1-40 years) compared to the 18 480 cancers expected; thus, the SIR was 1.12 [95% confidence interval (95% CI): 1.11-1.14]. The SIR associated with overweight and obesity was increased with concomitant comorbidities, like type 2 diabetes (SIR: 1.18; 95% CI: 1.13-1.23) and alcoholism-related diseases (SIR: 1.62; 95% CI: 1.45-1.82). The SIR was 1.31 (95% CI: 1.28-1.34) for cancers previously identified as obesity-related, including pancreatic (SIR: 1.38; 95% CI; 1.27-1.49) and postmenopausal breast cancer (SIR: 1.14; 95% CI: 1.09-1.19). Obesity/overweight status also elevated the SIRs for haematological (SIR: 1.24; 95% CI: 1.18-1.29) and neurological cancers (SIR: 1.19; 95% CI: 1.11-1.27]. In contrast, SIRs were 1.01 (95% CI: 0.97-1.05) for immune-related cancers, 0.88 (95% CI: 0.82-0.95) for malignant melanoma, and 0.88 (95% CI: 0.85-0.92) for hormone-related cancers, other than postmenopausal breast cancer. CONCLUSION: In this large cohort study, overweight and obesity was associated with increased risk of several common cancers.

Hyperkalaemia in people with diabetes: occurrence, risk factors and outcomes in a Danish population-based cohort study.

AIMS: To examine the incidence, risk factors and clinical outcomes of hyperkalaemia in people with diabetes in a real-world setting. METHODS: Using Danish health registries, we identified a population-based cohort of people with first-time drug-treated diabetes, in the period 2000-2012. First, the cumulative incidence of hyperkalaemia, defined as first blood test with potassium level >5.0 mmol/l after diabetes treatment initiation, was ascertained. Second, in a case-control analysis, risk factors were compared in people with vs without hyperkalaemia. Third, clinical outcomes were assessed among individuals with hyperkalaemia in a before-after analysis, and among people with and without hyperkalaemia in a matched cohort analysis. RESULTS: Of 68 601 individuals with diabetes (median age 62 years, 47% women), 16% experienced hyperkalaemia (incidence rate 40 per 1000 person-years) during a mean follow-up of 4.1 years. People who developed hyperkalaemia had a higher prevalence of chronic kidney disease [prevalence ratio 1.74 (95% CI 1.68-1.81)], heart failure [prevalence ratio 2.35 (95% CI 2.18-2.54)], use of angiotensin-converting enzyme inhibitors [prevalence ratio 1.24 (95% CI 1.20-1.28)], use of spironolactone [prevalence ratio 2.68 (95% CI 2.48-2.88)] and potassium supplements [prevalence ratio 1.59 (95% CI 1.52-1.67)]. In people with diabetes who developed hyperkalaemia, 31% were acutely hospitalized within 6 months before hyperkalaemia, increasing to 50% 6 months after hyperkalaemia [before-after risk ratio 1.67 (95% CI 1.61-1.72)]. The 6-month mortality rate after hyperkalaemia was 20%. Compared with matched individuals without hyperkalaemia, the hazard ratio for death was 6.47 (95% CI 5.81-7.21). CONCLUSIONS: One in six newly diagnosed people with diabetes experienced a hyperkalaemic event, which was associated with severe clinical outcomes and death.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Effectiveness of intensification therapies in Danes with Type 2 diabetes who use basal insulin: a population-based study.

AIMS: To examine the usage and real-life effectiveness of intensification therapies in people with Type 2 diabetes treated with basal insulin. METHODS: We used population-based healthcare databases in Denmark during 2000-2012 to identify all individuals with a first basal insulin prescription (with or without oral drugs), and evaluated subsequent intensification therapy with bolus insulin, premixed insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. Poisson regression was used to compute the adjusted relative risks of reaching glycaemic control targets. RESULTS: We included 7034 initiators of basal insulin (median age 64 years, diabetes duration 5.3 years, 84% with oral co-medication and median (interquartile range) pre-insulin HbA1c level 77 (65-92) mmol/mol [9.2% (8.1-10.6%)]. Of these, 3076 (43.7%) received intensification therapy after a median of 11 months: 58.5% with premixed insulin, 29.0% with bolus insulin, 10.6% with GLP-1 receptor agonists, and 1.9% with more than one add-on. Overall, 22% had attained an HbA1c level of < 53 mmol/mol (< 7%) by 3-6 months after intensification, while 38% attained an HbA1c < 58 mmol/mol (< 7.5%). Compared with premixed insulin intensification, attainment of HbA1c < 53 and < 58 mmol/mol was similar with bolus insulin add-on [adjusted relative risk 1.03 (95% CI 0.86-1.24) and 1.02 (95% CI 0.91-1.15), and higher for GLP-1 receptor agonist add-on [adjusted relative risk 1.56 (95% CI 1.27-1.92) and 1.27 (1.10-1.47)]. CONCLUSIONS: Among people with Type 2 diabetes, 22 and 38% reached a target HbA1c < 53 mmol/mol (< 7%) or < 58 mmol/mol (< 7.5%), respectively, after intensification of their basal insulin therapy. Compared with premixed insulin, target attainment was similar with bolus insulin and higher with GLP-1 receptor agonists.

Gender differences in the outcome of community-acquired Staphylococcus aureus bacteraemia: a historical population-based cohort study.

OBJECTIVES: Female gender has been suggested to be associated with poor outcome in patients with Staphylococcus aureus bacteraemia (SAB), but existing data remain sparse and conflicting. We investigated clinical outcomes in female and male patients with community-acquired (CA-) SAB. METHODS: Population-based medical registers were used to conduct a cohort study of all adult patients with CA-SAB in northern Denmark, 2000-2011. Thirty-day mortality after CA-SAB for female and male patients was estimated by the Kaplan-Meier method. Using Cox proportional hazards regression, we computed hazard ratios (HRs) of death according to gender, overall and stratified by age groups, co-morbidity level, and selected major diseases while adjusting for potential confounders. Moreover, we estimated 30-day prevalence proportions for SAB-associated infective endocarditis and osteomyelitis by gender. RESULTS: Among 2638 patients with CA-SAB, 1022 (39%) were female. Thirty-day mortality was 29% (n = 297) in female patients and 22% (n = 355) in male patients, yielding an adjusted HR (aHR) of 1.30 (95% CI, 1.11-1.53). This association appeared robust across age groups, whereas no consistent pattern was observed according to co-morbidity level. Compared with male patients, the prognostic impact of gender was most pronounced among female patients with diabetes (aHR 1.52; 95% CI 1.04-2.21)), and among female patients with cancer (aHR 1.40; 95% CI 1.04-1.90). The 30-day prevalence of infective endocarditis or osteomyelitis did not differ according to gender. CONCLUSION: Female patients with CA-SAB experienced increased 30-day mortality compared with male patients. Gender should be considered in the triage and risk stratification of CA-SAB patients.

Patient-level predictors of achieving early glycaemic control in Type 2 diabetes mellitus: a population-based study.

AIMS: To identify individual predictors of early glycaemic control in people with Type 2 diabetes mellitus after initiation of first glucose-lowering drug treatment in everyday clinical practice. METHODS: Using medical registries, we identified a population-based cohort of people with a first-time glucose-lowering drug prescription in Northern Denmark in the period 2000-2012. We used Poisson regression analysis to examine patient-level predictors of success in reaching early glycaemic control [HbA1c target of < 53 mmol/mol (7%)] < 6 months after treatment start. RESULTS: Among the 38 418 people (median age 63 years), 27 545 (72%) achieved early glycaemic control. The strongest predictor of achieving early control was pre-treatment HbA1c level; compared with a pre-treatment HbA1c level of ≤ 58 mmol/mol (7.5%), the adjusted relative risks of attaining early control were 0.63 (95% CI 0.61-0.64) for baseline HbA1c levels of > 58 and ≤ 75 mmol/mol (> 7.5 and ≤ 9%), and 0.58 (95% CI 0.57-0.59) for a baseline HbA1c level of > 9% (> 75 mmol/mol). All other examined predictors were only weakly associated with the chance of achieving early control. After adjustment, the only characteristics that remained independently associated with early control (in addition to high baseline HbA1c ) were being widowed (adjusted relative risk 0.95; 95% CI 0.93-0.97) and having a high Charlson comorbidity index score (score ≥ 3; adjusted relative risk 0.94; 95% CI 0.90-0.97). CONCLUSIONS: In a real-world clinical setting, people with Type 2 diabetes mellitus initiating glucose-lowering medication had a similar likelihood of achieving glycaemic control, regardless of sex, age, comorbidities and other individual factors; the only strong and potentially modifiable predictor was HbA1c before therapy start.

Functional status and quality of life after community-acquired bacteraemia: a matched cohort study.

Severe bacterial infections may have a prolonged negative effect on subsequent functional status and health-related quality of life. We studied hospitalized patients for changes in functional status and quality of life within 1 year of community-acquired bacteraemia in comparison to blood-culture-negative controls. In a prospectively conducted matched cohort study at Aalborg University Hospital, north Denmark, during 2011-2014, we included 71 medical inpatients with first-time community-acquired bacteraemia. For each bacteraemia patient, we matched one blood-culture-negative inpatient control on age and gender. Functional status and quality of life before and after hospitalization were assessed by Barthel-20 and EuroQol-5D questionnaires. We computed the 3-month and 1-year risk for any deterioration in Barthel-20 score and EuroQol-5D index score, and for a deterioration of ≥10 points in EuroQol-5D visual analogue scale score, and used regression analyses to assess adjusted risk ratios (RR) with 95% CIs. Compared with controls, bacteraemia was associated with an increased 3-month risk for deterioration in functional status as assessed by Barthel-20 score (14% versus 3% with deterioration, adjusted RR 5.1; 95% CI 1.2-22.3). The difference was less after 1 year (11% versus 7% with deterioration, adjusted RR 1.6; 95% CI 0.5-4.5). After 3 months, quality of life had become worse in 37% of bacteraemia patients and 28% of controls by EuroQol-5D index score (adjusted RR 1.3; 95% CI 0.8-2.1), with similar findings after 1 year and by visual analogue scale. In conclusion, community-acquired bacteraemia is associated with increased risk for subsequent deterioration in functional status compared with blood-culture-negative controls, and with a high risk for deterioration in quality of life.

Prescribing practices and clinical predictors of glucose-lowering therapy within the first year in people with newly diagnosed Type 2 diabetes.

AIM: To examine prescribing practices and predictors of glucose-lowering therapy within the first year following diagnosis of Type 2 diabetes mellitus in a clinical care setting. METHODS: We followed people enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort from outpatient hospital clinics and general practices throughout Denmark in 2010-2013. We used Poisson regression to compute age- and gender-adjusted risk ratios (RRs). RESULTS: Among 1158 new Type 2 diabetes mellitus patients, 302 (26%) did not receive glucose-lowering therapy within the first year, 723 (62%) received monotherapy [685 (95%) with metformin], and 133 (12%) received more than one drug. Predictors of receiving any vs. no therapy and combination vs. monotherapy were: age < 40 years [RR: 1.29 (95% CI: 1.16-1.44) and 3.60 (95% CI: 2.36-5.50)]; high Charlson Comorbidity Index [RRs: 1.20 (95% CI: 1.05-1.38) and 2.08 (95% CI: 1.16-3.72)]; central obesity [RRs: 1.23 (95% CI: 1.04-1.44) and 1.93 (95% CI: 0.76-4.94)]; fasting blood glucose of ≥ 7.5 mmol/l [RRs: 1.25 (95% CI: 1.10-1.42) and 1.94 (95% CI: 1.02-3.71)]; and HbA1c ≥ 59 mmol/mol (≥ 7.5%) [RR: 1.26 (95% CI: 1.20-1.32) and 2.86 (95% CI: 1.97-4.14)]. Weight gain ≥ 30 kg since age 20, lack of physical exercise and C-peptide of < 300 pmol/l also predicted therapy. CONCLUSIONS: Comorbidity, young age, central obesity and poor baseline glycaemic control are important predictors of therapy one year after Type 2 diabetes mellitus debut.

Early glycaemic control among patients with type 2 diabetes and initial glucose-lowering treatment: a 13-year population-based cohort study.

AIM: To examine real-life time trends in early glycaemic control in patients with type 2 diabetes between 2000 and 2012. METHODS: We used population-based medical databases to ascertain the association between achievement of glycaemic control with initial glucose-lowering treatment in patients with incident type 2 diabetes in Northern Denmark. Success in reaching glycated haemoglobin (HbA1c) goals within 3-6 months was examined using regression analysis. RESULTS: Of 38 418 patients, 91% started with oral glucose-lowering drugs in monotherapy. Metformin initiation increased from 32% in 2000-2003 to 90% of all patients in 2010-2012. Pretreatment (interquartile range) HbA1c levels decreased from 8.9 (7.6-10.7)% in 2000-2003 to 7.0 (6.5-8.1)% in 2010-2012. More patients achieved an HbA1c target of <7% (<53 mmol/mol) in 2010-2012 than in 2000-2003 [80 vs 60%, adjusted relative risk (aRR) 1.10, 95% confidence interval (CI) 1.08-1.13], and more achieved an HbA1c target of <6.5% [(<48 mmol/mol) 53 vs 37%, aRR 1.07 95% CI 1.03-1.11)], with similar success rates observed among patients aged <65 years without comorbidities. Achieved HbA1c levels were similar for different initiation therapies, with reductions of 0.8% (from 7.3 to 6.5%) on metformin, 1.5% (from 8.1 to 6.6%) on sulphonylurea, 4.0% (from 10.4 to 6.4%) on non-insulin combination therapies, and 3.8% (from 10.3 to 6.5%) on insulin monotherapy. CONCLUSIONS: Pretreatment HbA1c levels in patients with incident type 2 diabetes have decreased substantially, which is probably related to earlier detection and treatment in accordance with changing guidelines. Achievement of glycaemic control has improved, but 20% of patients still do not attain an HbA1c level of <7% within the first 6 months of initial treatment.

Trends in length of stay, mortality and readmission among patients with community-acquired bacteraemia.

In patients hospitalized with severe infection, premature discharge may lead to increased risk of readmission and death. We conducted this population-based cohort study to examine trends in length of stay (LOS) and 30-day mortality and hospital readmission rates after bacteraemia from 1994 through 2013. We used Cox regression to compute hazard ratios (HRs) for 30-day mortality and 30-day postdischarge readmission rates by calendar period and quintiles of LOS, adjusting for age, sex and comorbidity. Among 7618 patients hospitalized with community-acquired bacteraemia during the study period, median LOS decreased from 12 days (quartiles 7-21 days) in 1994-1998 to 9 days (quartiles 6-16 days) in 2009-2013 (25% relative reduction). The 30-day mortality fell from 16.7% to 15.0%, yielding an adjusted 30-day HR of 0.80 (95% confidence interval (CI) 0.68-0.95). Almost one fifth (19.4%) of patients discharged alive were readmitted within 30 days. Concurrently, the adjusted HR of readmission tended to increase (adjusted HR 1.09, 95% CI 0.93-1.28) in 2009-2013 compared with 1994-1998. Compared with the middle quintile of LOS (9-12 days), the risk of readmission was slightly higher for patients discharged within 5 days (adjusted HR 1.12, 95% CI 0.92-1.37), especially for readmission due to infection (adjusted HR 1.38, 95% CI 1.03-1.85). Readmission risk was lowest for 6 to 8 days LOS (adjusted HR 0.80, 95% CI 0.67-0.95) and highest for LOS ≥23 days (adjusted HR 1.30, 95% CI 1.11-1.53). The declining LOS after community-acquired bacteraemia between 1994 and 2013 was not accompanied by increased 30-day mortality but by slightly increased readmission rates.

Pneumonia and the incidence of cancer: a Danish nationwide cohort study.

OBJECTIVES: To examine the risk of a subsequent pulmonary or extra-pulmonary cancer diagnosis following a first-time hospital-based diagnosis of pneumonia. DESIGN: Population-based cohort study using Danish medical registries. SETTING: All hospitals in Denmark. SUBJECTS: A total of 342,609 patients with a first-time hospital-based (inpatient, emergency room or outpatient clinic) diagnosis of pneumonia between 1995 and 2011. MAIN OUTCOME MEASURES: We quantified the excess risk of various cancers amongst pneumonia patients compared to the expected risk in the general population, using relative [standardised incidence ratios (SIRs)] and absolute risk calculations. Follow-up started 1 month after a hospital-based diagnosis of pneumonia and ended on 31 December 2011. RESULTS: A total of 28,496 cancers were observed, compared with 21,625 expected, amongst 342,609 pneumonia patients followed for a median of 4.2 years. The absolute risk of a cancer diagnosis 1 to <6 months following a pneumonia diagnosis was 1.4%, with a corresponding SIR of 2.48 [95% confidence interval (CI) 2.41-2.55]. This was mainly due to an increased risk of lung cancer (eightfold) and haematological cancers (fourfold). The SIR for any cancer remained increased at 1.35 (95% CI 1.30-1.40) during 6-12 months of follow-up, and 1.20 (95% CI 1.18-1.22) during 1-5 years of follow-up. Beyond 5 years, an increased risk was maintained for lung, oesophageal, liver and bladder cancers, squamous cell carcinoma of the skin, lymphoma and multiple myeloma. CONCLUSIONS: A hospital-based pneumonia diagnosis was associated with an increased risk of a cancer diagnosis, especially in the ensuing months, but the absolute risk was small.

Tuberculosis and risk of cancer: a Danish nationwide cohort study.

OBJECTIVES: To investigate the short- and long-term risk of cancer in patients with active tuberculosis (TB). DESIGN: Using Danish nationwide databases, we quantified cancer risk in TB patients during 1978-2011 compared with the general population. RESULTS: We observed 1747 cancers in 15 024 TB patients (median follow-up 8.5 years), reflecting a standardised incidence ratio (SIR) of 1.52 (95%CI 1.45-1.59). All-time SIR for extra-pulmonary cancer was 1.29 (95%CI 1.22-1.36) and for lung cancer it was 3.40 (95%CI 3.09-3.74). Absolute cancer risk 3 months after TB was 1.83% (SIR 11.09, 95%CI 9.82-12.48), with highly increased SIRs for malignant pleural mesothelioma (368.4), lung cancer (40.9), Hodgkin's lymphoma (30.6), ovarian cancer (26.4) and non-Hodgkin's malignant lymphoma (23.8). Between the 3-month and 5-year follow-up, the SIR for any cancer was 1.59 (95%CI 1.46-1.72), including 19- and 3-fold increases for malignant pleural mesothelioma and lung cancer. Beyond 5 years, the SIR of cancer was 1.17 (95%CI 1.10-1.25). Elevated long-term risks persisted for haematological (SIR 1.34, 95%CI 1.01-1.74) and tobacco-related cancers (SIR 1.78, 95%CI 1.60-1.97). CONCLUSION: TB is a marker of occult lung cancer and several extra-pulmonary cancers. TB also predicts increased long-term risk of cancer, possibly related to chronic inflammation and shared risk factors, including immunosuppression and smoking.

Statin use and rupture of abdominal aortic aneurysm.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is associated with high mortality. Research suggests that statins may reduce abdominal aortic aneurysm (AAA) growth and improve rAAA outcomes. However, the clinical impact of statins remains uncertain in relation to both the risk and prognosis of rAAA. METHODS: This nationwide, population-based, combined case-control and follow-up study included all patients (aged at least 50 years) with a first-time hospital admission for rAAA and 1:1 matched AAA controls without rupture in Denmark from 1996 to 2008. Individual-level data on preadmission drug use, co-morbidities, socioeconomic markers, healthcare contacts and death were obtained from Danish nationwide registries. RESULTS: The study included 3584 cases and 3584 matched controls. Current statin use was registered for 418 patients with rAAA (11.7 per cent) and 539 AAA controls (15.0 per cent), corresponding to an age- and sex-matched odds ratio (OR) of 0.70 (95 per cent confidence interval (c.i.) 0.60 to 0.81) for rAAA in current statin users versus never users. The decreased risk of rAAA remained after adjustment for potential confounding factors (adjusted OR 0.73, 0.61 to 0.86). The overall 30-day mortality rate from time of hospital admission among patients with rAAA was 46.1 per cent in current statin users compared with 59.3 per cent in never users (adjusted mortality rate ratio (MRR) 0.80, 95 per cent c.i. 0.68 to 0.95). Patients who had formerly used statins did not have reduced mortality (adjusted MRR 0.98, 0.78 to 1.22). CONCLUSION: Statin use was associated with a reduced risk of rAAA and lower case fatality following rAAA. These results support current guidelines that recommend statin therapy in patients diagnosed with AAA.

Quality-of-care initiative in patients treated surgically for perforated peptic ulcer.

BACKGROUND: Mortality and morbidity are considerable after treatment for perforated peptic ulcer (PPU). Since 2003, a Danish nationwide quality-of-care (QOC) improvement initiative has focused on reducing preoperative delay, and improving perioperative monitoring and care for patients with PPU. The present study reports the results of this initiative. METHODS: This was a nationwide cohort study based on prospectively collected data, involving all hospitals caring for patients with PPU in Denmark. Details of patients treated surgically for PPU between September 2004 and August 2011 were reported to the Danish Clinical Register of Emergency Surgery. Changes in baseline patient characteristics and in seven QOC indicators are presented, including relative risks (RRs) for achievement of the indicators. RESULTS: The study included 2989 patients. An increasing number fulfilled the following four QOC indicators in 2010-2011 compared with the first 2 years of monitoring: preoperative delay no more than 6 h (59·0 versus 54·0 per cent; P = 0·030), daily monitoring of bodyweight (48·0 versus 29·0 per cent; P < 0·001), daily monitoring of fluid balance (79·0 versus 74·0 per cent; P = 0·010) and daily monitoring of vital signs (80·0 versus 68·0 per cent; P < 0·001). A lower proportion of patients had discontinuation of routine prophylactic antibiotics (82·0 versus 90·0 per cent; P < 0·001). Adjusted 30-day mortality decreased non-significantly from 2005-2006 to 2010-2011 (adjusted RR 0·87, 95 per cent confidence interval 0·76 to 1·00), whereas the rate of reoperative surgery remained unchanged (adjusted RR 0·98, 0·78 to 1·23). CONCLUSION: This nationwide quality improvement initiative was associated with reduced preoperative delay and improved perioperative monitoring in patients with PPU. A non-significant improvement was seen in 30-day mortality.

Alcohol drinking and risk of subsequent hospitalisation with pneumonia.

The dose-response relationship between alcohol consumption and pneumonia risk in healthy individuals is poorly understood. We examined 22,485 males and 24,682 females from Denmark who were aged 50-64 yrs. Subjects were without major chronic diseases at baseline and had a median follow-up of 12 yrs for first-time hospitalisation with pneumonia. 1,091 (males) and 944 (females) had pneumonia-related hospitalisation. Among males, the risk of pneumonia was increased for alcohol abstainers and those who drank large weekly amounts. The adjusted hazard ratios (HRs) for 0, 7-20, 21-34, 35-50 and >50 drinks·week(-1) were 1.49 (95% CI 1.00-2.21), 0.88 (95% CI 0.76-1.03), 0.87 (95% CI 0.72-1.05), 1.15 (95% CI 0.93-1.44) and 1.81 (95% CI 1.40-2.33), respectively, compared with 1-6 drinks·week(-1). The association between high alcohol intake and pneumonia persisted after controlling for subsequent chronic diseases. Among females, HRs for 0, 7-20, 21-35 and >35 drinks·week(-1) were 1.26 (95% CI 0.89-1.79), 1.01 (95% CI 0.88-1.17), 1.10 (95% CI 0.88-1.37) and 0.54 (95% CI 0.29-1.01), respectively. For the same moderate to high weekly alcohol amount, infrequent intake yielded higher pneumonia HRs than more regular intake in both sexes. Regular moderate alcohol intake is not associated with increased risk of hospitalisation for pneumonia. High weekly alcohol consumption in males and infrequent heavy drinking in both sexes may increase pneumonia risk.

The Peptic Ulcer Perforation (PULP) score: a predictor of mortality following peptic ulcer perforation. A cohort study.

BACKGROUND: Accurate and early identification of high-risk surgical patients with perforated peptic ulcer (PPU) is important for triage and risk stratification. The objective of the present study was to develop a new and improved clinical rule to predict mortality in patients following surgical treatment for PPU. DESIGN: nationwide cohort study based on prospectively collected data. SETTING: thirty-five hospitals in Denmark. PATIENTS: a total of 2668 patients surgically treated for gastric or duodenal PPU between 1 February 2003 and 31 August 2009. OUTCOME MEASURE: 30-day mortality. RESULTS: We derived a new clinical prediction rule for 30-day mortality and evaluated and compared its prognostic performance with the American Society of Anaesthesiologists (ASA) and Boey scores. A total of 708 patients (27%) died within 30 days of surgery. The Peptic Ulcer Perforation (PULP) score - comprised eight variables with an adjusted odds ratio of more than 1.28: 1) age > 65 years, 2) active malignant disease or AIDS, 3) liver cirrhosis, 4) steroid use, 5) time from perforation to admission > 24 h, 6) pre-operative shock, 7) serum creatinine > 130 µM, and 8) the four levels of the ASA score (from 2 to 5). The score predicted mortality well (area under receiver operating characteristics curve (AUC) 0.83). It performed considerably better than the Boey score (AUC 0.70) and better than the ASA score alone (AUC 0.78). CONCLUSION: The PULP score accurately predicts 30-day mortality in patients operated for PPU and can assist in risk stratification and triage.

Acute infections and venous thromboembolism.

BACKGROUND: Data on the association between acute infections and venous thromboembolism (VTE) are sparse. We examined whether various hospital-diagnosed infections or infections treated in the community increase the risk of VTE. METHODS: We conducted this population-based case-control study in Northern Denmark (population 1.8 million) using medical databases. We identified all patients with a first hospital-diagnosed VTE during the period 1999-2009 (n = 15 009). For each case, we selected 10 controls from the general population matched for age, gender and county of residence (n = 150 074). We identified all hospital-diagnosed infections and community prescriptions for antibiotics 1 year predating VTE. We used odds ratios from a conditional logistic regression model to estimate incidence rate ratios (IRRs) of VTE within different time intervals of the first year after infection, controlling for confounding. RESULTS: Respiratory tract, urinary tract, skin, intra-abdominal and bacteraemic infections diagnosed in hospital or treated in the community were associated with a greater than equal to twofold increased VTE risk. The association was strongest within the first 2 weeks after infection onset, gradually declining thereafter. Compared with individuals without infection during the year before VTE, the IRR for VTE within the first 3 months after infection was 12.5 (95% confidence interval (CI): 11.3-13.9) for patients with hospital-diagnosed infection and 4.0 (95% CI: 3.8-4.1) for patients treated with antibiotics in the community. Adjustment for VTE risk factors reduced these IRRs to 3.3 (95% CI: 2.9-3.8) and 2.6 (95% CI: 2.5-2.8), respectively. Similar associations were found for unprovoked VTE and for deep venous thrombosis and pulmonary embolism individually. CONCLUSIONS: Infections are a risk factor for VTE.