Readmission of older acutely admitted medical patients after short-term admissions in Denmark: a nationwide cohort study.

BACKGROUND: Knowledge of unplanned readmission rates and prognostic factors for readmission among older people after early discharge from emergency departments is sparse. The aims of this study were to examine the unplanned readmission rate among older patients after short-term admission, and to examine risk factors for readmission including demographic factors, comorbidity and admission diagnoses. METHODS: This cohort study included all medical patients aged ≥65 years acutely admitted to Danish hospitals between 1 January 2013 and 30 June 2014 and surviving a hospital stay of ≤24 h. Data on readmission within 30 days, comorbidity, demographic factors, discharge diagnoses and mortality were obtained from the Danish National Registry of Patients and the Danish Civil Registration System. We examined risk factors for readmission using a multivariable Cox regression to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for readmission. RESULTS: A total of 93,306 patients with a median age of 75 years were acutely admitted and discharged within 24 h, and 18,958 (20.3%; 95% CI 20.1 - 20.6%) were readmitted with a median time to readmission of 8 days (IQR 3 - 16 days). The majority were readmitted with a new diagnosis. Male sex (aHR 1.15; 1.11 - 1.18) and a Charlson Comorbidity Index ≥3 (aHR 2.28; 2.20 - 2.37) were associated with an increased risk of readmission. Discharge diagnoses associated with increased risk of readmission were heart failure (aHR 1.26; 1.12 - 1.41), chronic obstructive pulmonary disease (aHR 1.33; 1.25 - 1.43), dehydration (aHR 1.28; 1.17 - 1.39), constipation (aHR 1.26; 1.14 - 1.39), anemia (aHR 1.45; 1.38 - 1.54), pneumonia (aHR 1.15; 1.06 - 1.25), urinary tract infection (aHR 1.15; 1.07 - 1.24), suspicion of malignancy (aHR 1.51; 1.37 - 1.66), fever (aHR 1.52; 1.33 - 1.73) and abdominal pain (aHR 1.12; 1.05 - 1.19). CONCLUSIONS: One fifth of acutely admitted medical patients aged ≥65 were readmitted within 30 days after early discharge. Male gender, the burden of comorbidity and several primary discharge diagnoses were risk factors for readmission.

Overall risk and risk factors for metachronous peritoneal metastasis after colorectal cancer surgery: a nationwide cohort study.

BACKGROUND: This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M-PM) from colorectal cancer in patients who had intended curative treatment. METHODS: Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006-2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M-PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years. RESULTS: In 22 586 patients with colorectal cancer, the overall risk of M-PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M-PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour-involved resection margin (R1 versus R0) was associated with M-PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years. CONCLUSION: The overall risk of M-PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow-up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M-PM.

ANTECEDENTES: Este estudio tuvo como objetivo identificar la incidencia acumulada y los factores de riesgo de metástasis peritoneales metacrónicas (metachronous peritoneal metastases, M-PM) del cáncer colorrectal en pacientes que se sometieron al tratamiento curativo previsto. MÉTODOS: Se identificaron los pacientes con cáncer colorrectal a partir de la base de datos del grupo danés de cáncer colorrectal (Danish Colorectal Cancer Group) durante el periodo 2006-2015. El Registro Danés de Patología (Danish Pathology Registry) y el Registro Nacional Danés de Pacientes (Danish National Patient Registry) se utilizaron para identificar los casos de M-PM hasta el 2017. Los factores de riesgo se estimaron mediante una regresión de riesgo absoluto multivariable, tratando la muerte y otros tipos de cáncer como riesgos competitivos. El riesgo general y las diferencias de riesgo (risk differences, RD) se estimaron a 1, 3 y 5 años. RESULTADOS: De los 22.586 pacientes con CCR, el riesgo global de M-PM fue del 0,9% (i.c. del 95%: 0,8 a 1,0) al año, 1,9 (i.c. del 95%: 1,8 a 2,1) a los 3 años y 2,2 (i.c. del 95%: 2,0 a 2.4) después de 5 años. El estadio T tumoral avanzado ((y) pT4 versus (y) pT1) aumentó el riesgo de M-PM, DR a 1 año: 2,9% (i.c. del 95%: 2,1 a 3,), 3 años: 6,0 (i.c. 95% 4,9 a 7,2), así como la afectación de los ganglios linfáticos ((y) pN2 versus (y) pN0), 1 año: 2,5 (i.c. 95% 1,8 a 3,2), 3 años: 4,3 (i.c. 95% 3,2 a 5,3). No se observó un aumento adicional en la DR después de 5 años. Los márgenes de resección tumoral (R1 versus R0) se asociaron con una DR a 1 año de 3,9 (i.c. del 95% 1,6 a 6,2), y a 3 años de 5,9 (i.c. del 95% 2,6 a 9,3) de riesgo de M-PM en un subanálisis. CONCLUSIÓN: El riesgo global de M-PM en el cáncer colorrectal en pacientes es bajo, pero aumenta en las categorías de estadios T y N avanzados. Puede ser necesario un seguimiento de al menos 3 años después de la cirugía de CCR, dado el tratamiento potencialmente curativo de la M-PM diagnosticada precozmente.

Preadmission use of antidepressants and risk of complications and death after colorectal cancer surgery: a nationwide population-based cohort study.

AIM: Few studies have evaluated how preadmission use of antidepressants affects outcomes in colorectal cancer (CRC) patients after they have undergone surgery. Therefore, our aim is to examine whether preadmission use of antidepressants increased the risk of complications and death in patients who underwent CRC surgery. METHOD: Using the Danish Colorectal Cancer Group Database we identified patients who underwent CRC surgery in Denmark from 2005 to 2012. We identified prescriptions for antidepressants redeemed within 1 year prior to surgery and categorized patients as current users (≤ 90 days), former users (91-365 days) and nonusers. All patients were followed from surgery to 30 days thereafter or to death. We calculated 30-day rates of complications, intensive care unit (ICU) admission and mortality and compared these between users and nonusers using logistic and Cox regression adjusting for potential confounders. RESULTS: Of 27 374 patients, 8.9% were current users and 3.0% were former users. Antidepressant users were older and had more comorbidity but a similar cancer stage. Compared with nonusers, current users had a higher risk of postoperative reoperation [adjusted odds ratio (aORs) = 1.15 (95% CI 1.02-1.30)], medical complications [aORs = 1.41 (95% CI 1.25-1.60)] and increased ICU admission rate [adjusted hazard ratio (aHR) = 1.32 (95% CI 1.21-1.45)]. The 30-day mortality was 11.4% for current users, 9.1% for former users and 6.2% for nonusers [aHR = 1.34 (95% CI 1.17-1.53) for current vs nonusers]. CONCLUSION: Patients with preadmission use of antidepressants had a higher risk of complications and ICU admission, and higher 30-day mortality following CRC surgery than nonusers.

Out-of-hours intensive care unit admission and 90-day mortality: a Danish nationwide cohort study.

BACKGROUND: Mortality rates in critically ill adult patients admitted to the intensive care unit (ICU) remains high, and numerous patient- and disease-related adverse prognostic factors have been identified. In recent years, studies in a variety of emergency conditions suggested that outcome is dependent on the time of hospital admission. The importance of out-of-hours admission to the ICU has been sparsely evaluated and with ambiguous findings. We assessed the association between out-of-hours (16:00 to 07:00) and weekend admission to the ICU, respectively, and 90-day mortality in a nationwide cohort. METHODS: We included all Danish adult patients admitted to the ICU between 1 January 2011 and 30 June 2014, with an ICU stay > 24 h. The crude and adjusted association between out-of-hours and weekend admission and 90-day mortality was assessed (odds ratio (ORs) with 95% confidence intervals (CI)). RESULTS: A total of 44,797 patients were included, 53.3% were admitted out-of-hours, and 22.6% during weekends. Median age was 67 years (interquartile range (IQR) 55-76), and median SAPS II was 42 (IQR 30-54). Patients admitted in-hours vs. out-of-hours displayed a 90-day mortality rate of 41.0% vs. 44.2%. The adjusted association (OR with 95% CI) between out-of-hours admission and 90-day mortality was 1.07 (1.02-1.11), and the adjusted association (OR with 95% CI) between weekend admission and 90-day mortality was 1.10 (1.05-1.15). CONCLUSION: This nationwide study suggests that critically ill adult patients admitted to the ICU during weekends and out-of-hours, and with an ICU stay > 24 h are at slightly increased risk of mortality.

Impact of body mass index on risk of acute kidney injury and mortality in elderly patients undergoing hip fracture surgery.

The literature is limited regarding risk factors for acute kidney injury (AKI) and mortality in hip fracture patients, although AKI is common in these patients. While obese patients were at increased risk of AKI, underweight patients with and without AKI had elevated mortality for up to 1 year after hip fracture surgery, compared with normal-weight patients. INTRODUCTION: This study aimed to examine risk of postoperative AKI and subsequent mortality, by body mass index (BMI) level, in hip fracture surgery patients aged 65 and over. METHODS: A regional cohort study using medical databases was used. We included all patients who underwent surgery to repair a hip fracture during the years 2005-2011 (n = 13,529) at hospitals in Northern Denmark. We calculated cumulative risk of AKI by BMI level during 5 days postsurgery and subsequent short-term (6-30 days postsurgery) and long-term (31-365 days post-surgery) mortality. We calculated crude and adjusted hazard ratios (aHRs) for AKI and death with 95% confidence intervals (CIs), comparing underweight, overweight, and obese patients with normal-weight patients. RESULTS: Risks of AKI within five postoperative days were 11.9, 10.1, 12.5, and 17.9% for normal-weight, underweight, overweight, and obese patients, respectively. Among those who developed AKI, short-term mortality was 14.1% for normal-weight patients compared to 23.1% for underweight (aHR 1.7 (95% CI 1.2-2.4)), 10.7% for overweight (aHR 0.9 (95% CI 0.6-1.1)), and 15.2% for obese (aHR 0.9 (95% CI 0.6-1.4)) patients. Long-term mortality was 24.5% for normal-weight, 43.8% for underweight (aHR 1.6 (95% CI 1.0-2.6)), 20.5% for overweight (aHR 0.8 (95% CI 0.6-1.2)), and 21.4% for obese (aHR 1.1 (95% CI 0.7-1.8) AKI patients. Similar associations between BMI and mortality were observed among patients without postoperative AKI, although the absolute mortality risk estimates by BMI were considerably lower in patients without than in those with AKI. CONCLUSIONS: Obese patients were at increased risk of AKI compared with normal-weight patients. Among patients with and without postoperative AKI, overweight and obesity were not associated with mortality. Compared to normal-weight patients, underweight patients had elevated mortality for up to 1 year after hip fracture surgery irrespective of the presence of AKI. The absolute mortality risks were higher in all BMI groups with the presence of AKI.

Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK.

AIMS: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function. METHODS: Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels. RESULTS: In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis. CONCLUSIONS: Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.

Risk of acute renal failure and mortality after surgery for a fracture of the hip: a population-based cohort study.

AIMS: We examined risk of developing acute renal failure and the associated mortality among patients aged > 65 years undergoing surgery for a fracture of the hip. PATIENTS AND METHODS: We used medical databases to identify patients who underwent surgical treatment for a fracture of the hip in Northern Denmark between 2005 and 2011. Acute renal failure was classified as stage 1, 2 and 3 according to the Kidney Disease Improving Global Outcome criteria. We computed the risk of developing acute renal failure within five days after surgery with death as a competing risk, and the short-term (six to 30 days post-operatively) and long-term mortality (31 days to 365 days post-operatively). We calculated adjusted hazard ratios (HRs) for death with 95% confidence intervals (CIs). RESULTS: Among 13 529 patients who sustained a fracture of the hip, 1717 (12.7%) developed acute renal failure post-operatively, including 1218 (9.0%) with stage 1, 364 (2.7%) with stage 2, and 135 (1.0%) with stage 3 renal failure. The short-term mortality was 15.9% and 5.6% for patients with and without acute renal failure, respectively (HR 2.8, 95% CI 2.4 to 3.2). The long-term mortality was 25.0% and 18.3% for those with and without acute renal failure, respectively (HR 1.3, 95% CI 1.2 to 1.5). The mortality was higher in patients with an increased severity of renal failure. CONCLUSION: Acute renal failure is a common complication of surgery in elderly patients who sustain a fracture of the hip, and is associated with increased mortality up to one year after surgery despite adjustment for coexisting comorbidity and medication before surgery. Cite this article: Bone Joint J 2016;98-B:1112-18.

Preadmission use of selective serotonin reuptake inhibitors and short-term mortality in diabetic patients hospitalized due to stroke.

BACKGROUND: Patients with diabetes have an increased risk of stroke with a poor prognosis. Moreover, diabetic patients are at increased risk of depression and therefore likely to use selective serotonin reuptake inhibitors (SSRIs). We examined whether preadmission SSRI use was associated with increased mortality in diabetic patients hospitalized due to stroke. METHODS: Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetic patients in Denmark between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors. RESULTS: Amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischaemic stroke, 41.8% for intracerebral haemorrhage and 27.3% for subarachnoid haemorrhage). Amongst current SSRI users, 30-day stroke mortality was 23.3% (17.1% for ischaemic stroke, 50.7% for intracerebral haemorrhage and 28.6% for subarachnoid haemorrhage). Current SSRI use was associated with increased 30-day stroke mortality compared with nonuse [adjusted MRR 1.3, 95% confidence interval (CI) 1.1-1.5], with the highest risk observed amongst new users (MRR 1.5, 95% CI 1.2-1.8). Overall stroke mortality was driven by increased mortality due to ischaemic stroke, with adjusted MRRs of 1.3 (95% CI 1.1-1.7) for current users and 1.7 (95% CI 1.2-2.4) for new users. Propensity score-matched results were similar and robust across subgroups. CONCLUSION: In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischaemic stroke, compared with nonuse.

Chronic liver disease and 90-day mortality in 21,359 patients following peptic ulcer bleeding--a Nationwide Cohort Study.

BACKGROUND: Bleeding is a serious and frequent complication of peptic ulcer disease. Hepatic dysfunction can cause coagulopathy and increases the risk of peptic ulcer bleeding. However, whether chronic liver disease increases mortality after peptic ulcer bleeding remains unclear. AIM: To examine the prognostic impact of chronic liver disease on mortality after peptic ulcer bleeding. METHODS: We used population-based medical registries to conduct a cohort study of all Danish residents hospitalised with incident peptic ulcer bleeding from 2004 through 2011. We identified patients diagnosed with liver cirrhosis or non-cirrhotic chronic liver disease before their admission for peptic ulcer bleeding. We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan-Meier method (1 - survival function) and used a Cox regression model to estimate mortality rate ratios (MRRs), controlling for potential confounders. RESULTS: We identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these, 653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3% and 20.7%, respectively, compared to 18.3% among patients without chronic liver disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95% CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non-cirrhotic chronic liver disease. CONCLUSION: Patients with chronic liver disease, particularly liver cirrhosis, are at increased risk of death within 90 days after hospitalisation for peptic ulcer bleeding compared to patients without chronic liver disease.

Preadmission use of ACE inhibitors or angiotensin receptor blockers and short-term mortality after stroke.

BACKGROUND AND AIM: The prognostic impact of ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on stroke mortality remains unclear. We aimed to examine whether prestroke use of ACE-Is or ARBs was associated with improved short-term mortality following ischaemic stroke, intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH). METHODS: We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all first-time stroke patients during 2004-2012 and their comorbidities. We defined ACE-I/ARB use as current use (last prescription redemption <90 days before admission for stroke), former use and non-use. Current use was further classified as new or long-term use. We used Cox regression modelling to compute 30-day mortality rate ratios (MRRs) with 95% CIs, controlling for potential confounders. RESULTS: We identified 100 043 patients with a first-time stroke. Of these, 83 736 patients had ischaemic stroke, 11 779 had ICH, and 4528 had SAH. For ischaemic stroke, the adjusted 30-day MRR was reduced in current users compared with non-users (0.85, 95% CI 0.81 to 0.89). There was no reduction in the adjusted 30-day MRR for ICH (0.95, 95% CI 0.87 to 1.03) or SAH (1.01, 95% CI 0.84 to 1.21), comparing current users with non-users. No association with mortality was found among former users compared with non-users. No notable modification of the association was observed within sex or age strata. CONCLUSIONS: Current use of ACE-Is/ARBs was associated with reduced 30-day mortality among patients with ischaemic stroke. We found no association among patients with ICH or SAH.

Kidney disease and risk of venous thromboembolism: a nationwide population-based case-control study.

BACKGROUND: Chronic kidney disease is associated with hemostatic derangements, including both procoagulant activity and platelet dysfunction, which may influence the risk of venous thromboembolism. However, data associating kidney disease with risk of venous thromboembolism are sparse. OBJECTIVES: We examined whether kidney disease is associated with increased risk of venous thromboembolism. METHODS: We conducted this nationwide case-control study using data from medical databases. We included 128,096 patients with a hospital diagnosis of VTE in Denmark between 1980 and 2010 (54,473 had pulmonary embolism and 73,623 had deep venous thrombosis only) and 642,426 age- and gender-matched population controls based on risk-set sampling. We identified all previous hospital diagnoses of kidney disease, including nephrotic syndrome, glomerulonephritis without nephrotic syndrome, hypertensive nephropathy, chronic pyelonephritis/interstitial nephritis, polycystic kidney disease, diabetic nephropathy, or other kidney diseases. We used conditional logistic regression models to compute odds ratios (ORs) for venous thromboembolism with adjustment for potential confounders. RESULTS: Kidney disease was associated with an adjusted OR for venous thromboembolism ranging from 1.41 (95% CI, 1.22-1.63) for hypertensive nephropathy to 2.89 (95% CI, 2.26-3.69) for patients with nephrotic syndrome. The association was strongest within the first 3 months after a diagnosis of chronic kidney disease (adjusted OR for nephrotic syndrome = 23.23; 95% CI, 8.58-62.89), gradually declining thereafter. The risk, however, remained elevated for more than 5 years, especially in patients with nephrotic syndrome and glomerulonephritis. CONCLUSIONS: Kidney diseases, in particular nephrotic syndrome and glomerulonephritis, were associated with an increased risk of venous thromboembolism.

Mortality in elderly ICU patients: a cohort study.

BACKGROUND: The population is aging. We examined changes in the proportion of elderly (≥ 80 years) intensive care unit (ICU) patients during 2005-2011 and the association between age and mortality controlling for preexisting morbidity. METHODS: Through the Danish National Patient Registry, we identified a cohort of 49,938 ICU admissions (47,596 patients) in Northern Denmark from 2005 to 2011. Patients were subdivided in age groups (15-49, 50-64, 65-79 and ≥ 80 years) and calendar year. We estimated 30-day and 31-365-day mortality and mortality rate ratios (MRRs), stratified by admission type (medical and elective/acute surgical patients). Mortality was compared between age groups adjusting for sex and preexisting morbidity using 50-64-year-olds as reference. RESULTS: The proportion of elderly patients increased from 11.7% of all ICU patients in 2005 to 13.8% in 2011. Among the elderly, the 30-day mortality was 43.7% in medical, 39.6% in acute surgical, and 11.6% in elective surgical ICU patients. The corresponding adjusted 30-day MRRs compared with the 50-64-year-olds were 2.7 [95% confidence interval (CI) 2.5-3.0] in medical, 2.7 (95% CI 2.4-3.0) in acute surgical, and 5.2 (95% CI 4.1-6.6) in elective surgical ICU patients. The 31-365-day mortality among elderly patients was 25.4% in medical, 26.9% in acute, and 11.9% in elective surgical ICU patients, corresponding to adjusted MRRs of 2.5 (95% CI 2.1-2.9), 2.2 (95% CI 1.9-2.5), and 1.9 (95% CI 1.6-2.3), respectively. CONCLUSIONS: During 2005-2011, there was an 18% increase in the proportion of elderly ICU patients. Advancing age is associated with increased mortality even after controlling for preexisting morbidity.

Methods to assess seasonal effects in epidemiological studies of infectious diseases--exemplified by application to the occurrence of meningococcal disease.

Seasonal variation in occurrence is a common feature of many diseases, especially those of infectious origin. Studies of seasonal variation contribute to healthcare planning and to the understanding of the aetiology of infections. In this article, we provide an overview of statistical methods for the assessment and quantification of seasonality of infectious diseases, as exemplified by their application to meningococcal disease in Denmark in 1995-2011. Additionally, we discuss the conditions under which seasonality should be considered as a covariate in studies of infectious diseases. The methods considered range from the simplest comparison of disease occurrence between the extremes of summer and winter, through modelling of the intensity of seasonal patterns by use of a sine curve, to more advanced generalized linear models. All three classes of method have advantages and disadvantages. The choice among analytical approaches should ideally reflect the research question of interest. Simple methods are compelling, but may overlook important seasonal peaks that would have been identified if more advanced methods had been applied. For most studies, we suggest the use of methods that allow estimation of the magnitude and timing of seasonal peaks and valleys, ideally with a measure of the intensity of seasonality, such as the peak-to-low ratio. Seasonality may be a confounder in studies of infectious disease occurrence when it fulfils the three primary criteria for being a confounder, i.e. when both the disease occurrence and the exposure vary seasonally without seasonality being a step in the causal pathway. In these situations, confounding by seasonality should be controlled as for any confounder.

Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study.

BACKGROUND: There is conflicting evidence regarding bisphosphonates and atrial fibrillation (AF) risk in osteoporosis patients. However, bisphosphonates are used in much higher doses in treatment of bone metastasis and hypercalcemia, but little is known about the AF risk in cancer patients. METHODS: We conducted a nationwide population-based cohort study using Danish databases. All cancer patients exposed to intravenous bisphosphonates during 2000-2008 were matched with two non-exposed cancer patients by cancer type, distant metastasis presence at diagnosis, age, and gender. We used Cox proportional hazard regression to estimate hazards ratios (HRs) of AF/flutter adjusting for important confounding factors. RESULTS: Of the 3981 cancer patients exposed to intravenous bisphosponates, 128 (3.2%) developed AF/flutter. This condition occurred in 192 (2.4%) of the 7906 non-exposed cancer patients, corresponding to an adjusted HR of 1.7 (95% CI: 1.2-2.4). CONCLUSION: Intravenous bisphosphonates may increase AF/flutter risk in cancer patients.

The impact of pre-admission morbidity level on 3-year mortality after intensive care: a Danish cohort study.

BACKGROUND: Chronic diseases are common among intensive care unit (ICU) patients and may worsen their prognosis. We examined the prevalence and impact of pre-admission/index morbidity among ICU patients compared with a general population cohort. METHODS: Our study encompassed all 28,172 adult patients admitted to ICUs in northern Denmark in 2005-2007 and 281,671 age- and sex-matched individuals from the general population. We used a nationwide hospital registry to obtain a 5-year history of 19 chronic diseases and computed Charlson Comorbidity Index (CCI) for each study participant and grouped them into low (CCI=0), moderate (CCI=1-2), and high (CCI=3+) morbidity levels. We computed mortality and mortality rate ratios (MRRs) adjusted for confounders, and compared the mortality between ICU patients and the general population cohort. RESULTS: Low, moderate, and high pre-admission morbidity levels were present in 51.5%, 34.1%, and 14.4% of ICU patients, respectively. In these groups, 30-day mortality was 10.8%, 18.4%, and 26.7%, respectively. Three-year mortality was 21.3%, 43.1%, and 63.2%, respectively. The adjusted 30-day MRR was 1.30 [95% confidence intervals (CI): 1.21-1.39] and 1.86 (95% CI: 1.71-2.01) for ICU patients with moderate and high morbidity levels, both compared with a low morbidity level. The general population had a lower morbidity level and mortality at all morbidity levels throughout the study period. Interaction between ICU admission and high morbidity level added 5.1% to the mortality during the second and third year of follow-up. CONCLUSION: A high pre-admission morbidity level was frequent among ICU patients and associated with a worsened prognosis. Morbidity had more impact on mortality among ICU patients compared with a general population cohort.

Non-steroidal anti-inflammatory drug use and risk of venous thromboembolism.

BACKGROUND: The association between the use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2-selective inhibitors (COX2Is) and the risk of venous thromboembolism (VTE) remains unclear. OBJECTIVES: To examine this association. PATIENTS/METHODS: We conducted a population-based case-control study in northern Denmark (population of 1.7 million). Using the National Patient Registry, we identified patients with a first hospital VTE diagnosis during 1999-2006 (n = 8368) and their comorbidities. For each case, we selected 10 controls (n = 82, 218) matched by age and sex. From the prescription database, we ascertained the use of NSAIDs at the time of diagnosis (current use) or before (recent use), and comedications. Current use was further classified as new use (first-ever prescription redemption within 60 days before diagnosis date) or long-term use. We used odds ratios from a logistic regression model to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: As compared with no use, the adjusted IRR associating current non-selective NSAID use with VTE was 2.51 (95% CI 2.29-2.76), and that for current COX2I use was 2.19 (95% CI 1.99-2.41). Recent users had substantially smaller increases than current users. The adjusted IRRs among long-term users were 2.06 for non-selective NSAIDs (95% CI 1.85-2.29) and 1.92 for COX2Is (95% CI 1.72-2.15). Similarly increased risks were found for unprovoked VTE (occurrence in the absence of pregnancy, cancer, major trauma, fracture or surgery within 3 months preceding the VTE), deep vein thrombosis, pulmonary embolism, and individual NSAIDs. CONCLUSIONS: The use of non-selective NSAIDs or COX2Is was associated with a two-fold or more increased risk of VTE.

Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study.

SUMMARY BACKGROUND: Antiplatelet drug use increases bleeding risk, but its role in precipitating subarachnoid hemorrhage remains unclear. OBJECTIVES: We examined whether the use of low-dose acetylsalicylic acid (LDA), clopidogrel or dipyridamole increased the risk of subarachnoid hemorrhage. PATIENTS/METHODS: This population-based case-control study was conducted in northern Denmark. We used the Danish National Patient Registry to identify all persons admitted to neurosurgery or neurology departments with a first diagnosis of subarachnoid hemorrhage between 1997 and 2008 (n = 1186). Using risk-set sampling, we selected 10 population controls (n = 11 840) for each case, matched by age and sex. We obtained data on prescriptions for antiplatelet drugs, use of other medications and comorbidity from medical databases. We used conditional logistic regression to compute odds ratios with 95% confidence intervals (CIs), controlling for confounding factors. RESULTS: One hundred and nine cases (9.2%) and 910 controls (7.7%) used antiplatelet drugs. Among cases, 104 (8.8%) used LDA and 11 (0.9%) used dipyridamole. Among controls, 891 (7.5%) used LDA and 48 (0.4%) used dipyridamole. As compared with not using any antiplatelet drugs during the study period, the adjusted odds ratios were 1.03 (95% CI 0.81-1.32) for long-term LDA use, 2.52 (95% CI 1.37-4.62) for new LDA use, and 2.09 (95% CI 1.04-4.23) for long-term dipyridamole use. Owing to the low number of users, data were inconclusive for clopidogrel. CONCLUSIONS: Long-term dipyridamole use and new LDA use were associated with an increased risk of subarachnoid hemorrhage. Because of the limited precision of these risk estimates, however, caution is advised in their interpretation. Long-term LDA use was not associated with subarachnoid hemorrhage.