Studies on long-term mortality after venous thromboembolism (VTE) are sparse.
Using Danish medical databases, we conducted a 30-year nationwide population-based cohort study of 128 223 patients with first-time VTE (1980-2011) and a comparison cohort of 640 760 people from the general population (without VTE) randomly matched by sex, year of birth, and calendar period. The mortality risks for patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (3.0% and 31% versus 0.4%). Using Cox regression, we assessed mortality rate ratios (MRRs) with 95% confidence intervals (CIs). The overall 30-year MRR was 1.55 (95% CI, 1.53-1.57) for DVT and 2.77 (95% CI, 2.74-2.81) for PE. The 30-day MRR was 5.38 (95% CI, 5.00-5.80) for DVT and 80.87 (95% CI, 76.02-86.02) for PE. Over time, the 30-day MRR was consistently 5- to 6-fold increased for DVT, whereas it improved for PE from 138 (95% CI, 125-153) in 1980 to 1989 to 36.08 (95% CI, 32.65-39.87) in 2000 to 2011. The 1- to 10-year and 11- to 30-year MRRs remained 25% to 40% increased after both DVT and PE but were 3- to 5-fold increased after DVT and 6- to 11-fold increased after PE when VTE was considered the immediate cause of death.
Patients with VTE are at increased risk of dying, especially within the first year after diagnosis, but also during the entire 30 years of follow-up, with VTE as an important cause of death. Although 30-day mortality after DVT remained fairly constant over the last 3 decades, it improved markedly for PE.
Comparison of outcomes of patients = 80 years of age having percutaneous coronary intervention according to presentation (stable vs unstable angina pectoris/non-ST-segment elevation myocardial infarction vs ST-segment elevation myocardial infarction).
Patients = 80 years old with coronary artery disease constitute a particular risk group in relation to percutaneous coronary intervention (PCI). From 2002 through 2008 we examined the annual proportion of patients = 80 years old undergoing PCI in western Denmark, their indications for PCI, and prognosis. From 2002 through 2009 all elderly patients treated with PCI were identified in a population of 3.0 million based on the Western Denmark Heart Registry. Cox regression analysis was used to compare mortality rates according to clinical indications controlling for potential confounding. In total 3,792 elderly patients (= 80 years old) were treated with PCI and the annual proportion increased from 224 (5.4%) in 2002 to 588 (10.2%) in 2009. The clinical indication was stable angina pectoris (SAP) in 30.2%, ST-segment elevation myocardial infarction (STEMI) in 35.0%, UAP/non-STEMI in 29.7%, and "ventricular arrhythmia or congestive heart failure" in 5.1%. Overall 30-day and 1-year mortality rates were 9.2% and 18.1%, respectively. Compared to patients with SAP the adjusted 1-year mortality risk was significantly higher for patients presenting with STEMI (hazard ratio 3.86, 95% confidence interval 3.08 to 4.85), UAP/non-STEMI (hazard ratio 1.95, 95% confidence interval 1.53 to 2.50), and ventricular arrhythmia or congestive heart failure (hazard ratio 2.75, 95% confidence interval 1.92 to 3.92). In patients with SAP target vessel revascularization decreased from 7.1% in 2002 to 2.5% in 2008. In conclusion, the proportion of patients = 80 years old treated with PCI increased significantly over an 8-year period. Patients with SAP had the lowest mortality rates and rates of clinically driven target vessel revascularization decreased over time.
• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the interaction effect.
• Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of major adverse cardiovascular events within 12 months after coronary stent implantation. • Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of major adverse cardiovascular events in patients using clopidogrel after coronary stent implantation.
To examine whether CYP3A4-metabolizing statin use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation, using time-varying drug exposure ascertainment.
We conducted this population-based cohort study in Western Denmark (population: 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12 months of follow-up, we tracked the use of clopidogrel and CYP3A4-metabolizing statins and the rate of MACE. We used Cox regression to compute hazard ratios (HRs) controlling for potential confounders.
The rate of MACE per 1000 person years was 104 for concomitant clopidogrel and statin use, 130 for clopidogrel without statin use, 108 for statin without clopidogrel use and 446 for no use of either drug. The adjusted HR comparing clopidogrel use with non-use was 0.68 (95% confidence interval (CI) 0.58, 0.79) among statin users and 0.34 (95% CI 0.29, 0.40) among statin non-users, yielding an interaction effect (i.e. relative rate increase) of 1.97 (95% CI 1.59, 2.44). The adjusted HR for MACE comparing statin use with non-use was 0.97 (95% CI 0.83, 1.13) among clopidogrel users and 0.49 (95% CI 0.42, 0.57) among clopidogrel non-users.
Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of MACE within 12 months after coronary stent implantation. Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of MACE in patients using clopidogrel after coronary stent implantation.
In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only.
From January 2002 to June 2009 all patients treated with PPCI were identified from the Western Denmark Heart Registry. We examined mortality according to timing of multivessel PCI: acute procedure, staged procedure during the index hospitalisation, or staged procedure performed within 60 days. The hazard ratio (HR) for death was estimated using a time-dependent Cox regression model, with time of PCI for the non-culprit lesion as the time-dependent variable. The study cohort consisted of 5,944 patients, of whom 4,770 (80%) had single-vessel disease and 1,174 (20%) had multivessel PCI within 60 days. Among 354 (30.2%) patients with acute multivessel PCI, 194 (16.5%) patients with multivessel PCI during the index hospitalisation, and 626 (53.3%) patients with multivessel PCI within 60 days after the index hospitalisation, the adjusted HRs for one-year mortality were 1.53 (95% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease.
Acute multivessel PCI in patients with STEMI was associated with increased mortality.
OBJECTIVES: To analyse the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure (TCF) in individuals infected with HIV. DESIGN: Population-based observational cohort study from 1 January 1995 to 31 December 2003, focusing on all 2722 recipients of highly active antiretroviral therapy (HAART) in Denmark. METHODS: We used person-years analysis, Kaplan-Meier survival curves and Cox regression analysis. TCF was defined as a minimum of 120 days with viral load > 1000 copies/ml on treatment with each of the three major drug classes. RESULTS: We observed 177 TCFs, yielding a crude incidence rate (IR) of 1.8 per 100 person-years [95% confidence interval (CI), 1.6-2.1]. Seven years after initiation of HAART, 17.2% (95% CI, 14.5-20.5) of antiretroviral (ART)-experienced patients, but only 7.0% (95% CI, 4.3-11.2) of ART-naive patients were estimated to have failed. After an initial rise, the IR from the third to the sixth year of HAART declined significantly for ART-experienced patients [incidence rate ratio (IRR), 0.80 per year (95% CI, 0.66-0.97); P = 0.022], and non-significantly for ART-naive patients [IRR, 0.79 per year (95% CI, 0.53-1.18); P = 0.255]. The IR for all patients being followed each year declined from 1997 to 2003 [IRR, 0.88 (95% CI, 0.81-0.96); P = 0.002]. The prevalence of TCF remained stable at less than 7% after 2000. Predictors of TCF at commencement of HAART were a CD4 cell count below 200, a previous AIDS-defining event, previous antiretroviral exposure, earlier year of HAART initiation, and young age. CONCLUSIONS: The risk of TCF is declining in Denmark and the prevalence remains stable.
To examine the association between exacerbation frequency and mortality following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
Cohort study using medical databases.
On 1 January 2005, we identified all patients with prevalent hospital-diagnosed chronic obstructive pulmonary disease (COPD) who had at least one AECOPD during 1 January 2005 to 31 December 2009. We followed patients from the first AECOPD during this period until death, emigration or 31 December 2009, whichever came first. We flagged all AECOPD events during follow-up and characterised each by the exacerbation frequency (0, 1, 2 or 3+) in the prior 12-month period.
Using Cox regression, we computed 0-30-day and 31-365-day age-adjusted, sex-adjusted, and comorbidity-adjusted mortality rate ratios (MRRs) with 95% CIs entering exacerbation frequency as a time-varying exposure.
We identified 16,647 eligible patients with prevalent COPD, of whom 6664 (40%) developed an AECOPD and were thus included in the study cohort. The 0-30-day MRRs were 0.97 (95% CI 0.80 to 1.18), 0.90 (95% CI 0.70 to 1.15) and 1.03 (95% CI 0.81 to 1.32) among patients with AECOPD with 1, 2 and 3+ AECOPDs versus no AECOPD within the past 12 months, respectively. The corresponding MRRs were 1.47 (95% CI 1.30 to 1.66), 1.89 (95% CI 1.59 to 2.25) and 1.59 (95% CI 1.23 to 2.05) for days 31-365.
Among patients with AECOPD, one or more exacerbations in the previous year were not associated with 30-day mortality but were associated with an increased 31-365-day mortality.
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Proton pump inhibitors (PPIs) are increasingly used in reflux disease treatment also among pregnant women. Hypospadias prevalence is increasing and the birth defect is diagnosed in 0.3%-0.8% of male births, but the association with maternal PPI use during pregnancy is virtually unknown. Therefore, we decided to estimate the hypospadias risk in male offspring after maternal PPI use during pregnancy. We used Danish nationwide registries to conduct a population-based prevalence study including all live-born boys from 1997 through 2009. Maternal PPI use was classified according to exposure time: early pregnancy (30 days before conception through the end of the first trimester) and entire pregnancy (30 days before and throughout pregnancy). Outcome was defined as a hospital hypospadias diagnosis recorded any time after delivery. We calculated prevalence ratios and 95% confidence intervals associating maternal PPI use with hypospadias in male offspring using Cox proportional hazard regression analysis and adjusted for confounding factors. We identified a total of 430,569 live-born boys of whom 2926 were exposed to maternal PPI use during early pregnancy. Among the exposed boys, 20 (0.7%) were diagnosed with hypospadias, whereas 2683 (0.6%) of the nonexposed had hypospadias (adjusted prevalence ratio = 1.1; 95% confidence interval, 0.7-1.7). A total of 5227 boys were exposed during the entire pregnancy, and 32 (0.6%) had hypospadias corresponding to a prevalence ratio of 1.0 (95% confidence interval, 0.7-1.4). The subanalysis restricted to omeprazole exposure showed similar results. We thus conclude that maternal PPI use during pregnancy was not associated with hypospadias in boy offspring.
HIV-infected persons are at increased risk of pneumonia, even with highly active antiretroviral treatment (HAART). We examined the impact of pneumonia on mortality and identified prognostic factors for death among HIV-infected.
In a nationwide, population-based cohort of individuals with HIV, we included persons hospitalized with pneumonia from the Danish National Hospital Registry and obtained mortality data from the Danish Civil Registration System. Comparing individuals with and without pneumonia, we used Poisson regression to estimate relative mortality and logistic regression to examine prognostic factors for death following pneumonia. From January 1, 1995, to July 1, 2008, we observed 699 episodes of first hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%-28.9%) in 1995-1996 to 8.4% (95% CI: 6.1%-11.6%) in 2000-2008. Mortality remained elevated for more than a year after hospitalization for pneumonia: adjusted mortality rate ratio 5.38 (95% CI: 4.27-6.78), 1.80 (95% CI: 1.36-2.37), and 1.62 (95% CI: 1.32-2.00) for days 0-90, 91-365, and 366+, respectively. The following variables predicted mortality within 90 days following hospitalization for pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37-10.4), Charlson Comorbidity Index score > or = 2 (3.86, 95% CI: 2.19-6.78); no current HAART (3.58, 95% CI: 1.83-6.99); history of AIDS (2.46, 95% CI: 1.40-4.32); age per 10 year increase (1.43, 95% CI: 1.11-1.85); and CD4+ cell count
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Is there an association between oral contraceptive (OC) use (age at the start of use, duration of use, ethinylestradiol dose and generation) and time to pregnancy (TTP)?
Although OC use was associated with a transient delay in the return of fertility, we found no evidence that long-term OC use deleteriously affects fecundability.
Studies using retrospective data on TTP have reported a short-term delay in the return of fertility after OC use. However, little is known about the long-term OC use and TTP.
Data were derived from 'Snart Gravid.dk', a prospective cohort study that enrolled participants from 1 June 2007 to 31 May 2010. The final study population consisted of 3727 women.
Eligible women were Danish pregnancy planners, aged 18-40 years, who completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or for 12 months, whichever came first. Cohort retention was 80%. We used proportional probability regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), with adjustment for potential confounders.
Compared with barrier methods, the use of OCs as the last contraception method before attempting to conceive was associated with a short-term delay in return of fertility (FR = 0.87, 95% CI: 0.79-0.96). Longer term OC use was associated with higher fecundability: compared with OC use for less than 2 years; FRs were 0.98 (95% CI: 0.83-1.15) for 2-3 years, 1.16 (95% CI: 0.98-1.37) for 4-5 years, 1.10 (95% CI: 0.93-1.29) for 6-7 years, 1.17 (95% CI: 0.99-1.38) for 8-9 years, 1.23 (95% CI: 1.04-1.46) for 10-11 years and 1.28 (95% CI: 1.07-1.53) for =12 years of OC use.
Because this was a non-experimental study, where study volunteers provided information about their history of contraceptive use at baseline and were followed prospectively to assess their waiting times to pregnancy, there was some potential for error in the reporting of OC use and TTP. Nevertheless, participants reported data on OC use before the occurrence of pregnancy, thereby reducing the potential for systematic bias.
Women who have used OCs for many years should be reassured as there was no evidence that long-term OC use has a deleterious affects on fecundability. Both short- and long-term OC users are likely to experience a transient delay in conception compared with those discontinuing barrier methods.
This study was supported by the National Institute of Child Health and Human Development (R21050264) and the Danish Medical Research Council (271-07-0338). The authors declare that there are no conflicts of interest.
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BACKGROUND/AIMS: Patients with liver cirrhosis and ascites have a high risk of spontaneous bacterial peritonitis, but the prognostic impact of spontaneous bacterial peritonitis has not been well examined. METHODOLOGY: Patients with liver cirrhosis and ascites were included at the time of their first paracentesis during hospitalization in the Department of Hepatology, Aarhus University Hospital, Denmark, between September 1992 and September 2000. Cox regression was used to estimate the mortality of patients with spontaneous bacterial peritonitis (ascites leukocyte count > or = 250 per mm3) relative to controls without spontaneous bacterial peritonitis. Furthermore, we used Cox regression to estimate the change in mortality when controls developed spontaneous bacterial peritonitis during follow-up. RESULTS: Of 286 patients, 76 (27%) had spontaneous bacterial peritonitis at the first paracentesis. The mortality ratio of patients with spontaneous bacterial peritonitis relative to controls was 1.0 (95% confidence interval 0.7-1.5) after adjustment for age, gender, comorbidity, and alcohol abuse. Of the 210 controls, 42 (20%) were found to have spontaneous bacterial peritonitis at a later paracentesis. Their mortality rate more than doubled with the onset of spontaneous bacterial peritonitis. CONCLUSIONS: Spontaneous bacterial peritonitis at the first paracentesis did not affect the prognosis of patients with liver cirrhosis, whereas development of spontaneous bacterial peritonitis during follow-up doubled the mortality risk. This may be due to a longer diagnostic delay in those who developed spontaneous bacterial peritonitis during follow-up.