Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis

BACKGROUND: Venous thromboembolism (VTE) remains a major cause of morbidity following stroke. The optimal form of pharmacologic prophylaxis following stroke is unknown. METHODS: We identified randomized trials comparing unfractionated heparin (UFH) to low-molecular-weight heparin (LMWH) for VTE prevention in ischemic stroke patients. We focused on the risk for VTE, pulmonary embolism (PE), bleeding, and mortality as a function of the type of agent used for prophylaxis. Findings were pooled with a random-effects model. RESULTS: We identified three trials including 2,028 patients. Two of the studies were blinded, two studies relied on enoxaparin, while one study utilized certoparin. In two studies, UFH was administered three times a day, while it was administered twice daily in the remaining study. The use of LMWH was associated with a significant risk reduction for any VTE (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41 to 0.70; p < 0.001). Limiting the analysis to proximal VTEs also indicated that LMWHs were superior (OR with LMWH vs UFH, 0.53; 95% CI, 0.37 to 0.75; p < 0.001). LMWH use led to fewer PEs as well (OR, 0.26; 95% CI, 0.07 to 0.95; p = 0.042). There were no differences in rates of overall bleeding, intracranial hemorrhage, or mortality based on the type of agent employed. Restricting the analysis to the reports employing enoxaparin did not alter our findings. CONCLUSIONS: The prophylactic use of LMWH compared to UFH following ischemic stroke is associated with a reduction in both VTE and PE. This benefit is not associated with an increased incidence of bleeding. Broader use of LMWH for VTE prevention after ischemic stroke is warranted.     

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.     

Bed rest or ambulation in the initial treatment of patients with acute deep vein thrombosis or pulmonary embolism: findings from the RIETE registry

BACKGROUND: Traditionally, many patients with acute deep vein thrombosis (DVT) are treated not only by anticoagulation therapy but additionally by strict bed rest, which is aimed at reducing the risk of pulmonary embolism (PE) events. However, this risk has not been subjected to empirical verification. PATIENTS AND METHODS: The Registro Informatizado de la Enfermedad TromboEmbólica is a Spanish registry of consecutively enrolled patients with objectively confirmed, symptomatic acute DVT or PE. In this analysis, the clinical characteristics, details of anticoagulant therapy, and clinical outcomes of enrolled patients with and without strict bed rest prescribed during the first 15 days were compared. Patients in whom ambulation was not possible were not included in this analysis. RESULTS: A total of 2,650 patients entered the study (DVT, 2,038 patients; PE, 612 patients). Of these patients, 1,050 DVT patients (52%) and 385 PE patients (63%) were prescribed strict bed rest. New events of symptomatic, objectively confirmed PE developed during the 15-day study period in 11 patients with DVT (0.5%) and 4 patients with PE (0.7%). Five of these 15 patients (33%) died as a result of their PE. Age < 65 years (odds ratio [OR], 3.1; 95% confidence interval [CI], 0.98 to 11) and cancer (OR, 3.0; 95% CI, 0.98 to 9.1) were associated with an increased rate of new PEs. There were not significant differences between bedridden and ambulant patients in terms of new PE events, fatal PE, or bleeding complications. CONCLUSIONS: Our findings confirm those from previous reports suggesting that bed rest has no influence on the risk of developing PE among patients with acute DVT of the lower limbs. In addition, our findings show for the first time the lack of influence of bed rest even in patients presenting with acute submassive PE.     

Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis

OBJECTIVES: Prophylaxis with unfractionated heparin (UFH) has been proven to reduce rates of venous thromboembolism (VTE) in hospitalized medical patients. While twice-daily (BID) and three-times-daily (TID) dosing regimens have been studied, the two have never been directly compared. We performed a metaanalysis to assess whether TID is superior to BID dosing in the prevention of VTE. METHODS: Medline, EMBASE, and Cochrane Controlled Trials Register from 1966 through December 2004 were searched for randomized trials comparing subcutaneously dosed UHF (either BID or TID) with placebo or control for VTE prophylaxis in medical patient populations. Two reviewers independently rated study quality on the basis of predetermined criteria. Data were extracted on patient age, hospital setting, comorbidities, VTE rates, and bleeding complications. RESULTS: Twelve studies were identified; 7,978 patients (1,664 patients in the TID arm, and 6,314 patients in the BID arm) were included. After adjustment for baseline risk, there was no difference in the overall rate (per 1,000 patient-days) of VTE (BID, 5.4; vs TID, 3.5; p = 0.87). TID heparin showed a trend toward a decrease in pulmonary embolism (PE) [BID, 1.5; vs TID, 0.5; p = 0.09] and in proximal DVT and PE (BID, 2.3; vs TID, 0.9; p = 0.05). The risk for major bleeding was significantly increased with TID heparin (BID, 0.35; vs TID, 0.96; p < 0.001). CONCLUSIONS: BID heparin dosing causes fewer major bleeding episodes, while TID dosing appears to offer somewhat better efficacy in preventing clinically relevant VTE events. Practitioners should use underlying risk for VTE and bleeding to individualize pharmacologic prevention.     

Acute pulmonary embolism is an independent predictor of adverse events in severe decompensated heart failure patients

BACKGROUND: Congestive heart failure (CHF) is a well-recognized risk factor for venous thromboembolism (VTE) and is associated with higher mortality in patients with an acute pulmonary embolism (PE). There are very few data on how acute PE affects the clinical course of patients with heart failure. The purpose of this study was to determine the impact of an acute PE on the short-term prognosis of patients hospitalized for decompensated CHF. METHODS: This was a prospective cohort study of 198 patients admitted to a coronary care unit between July 2001 and March 2003 with severe decompensated CHF. The primary outcome measure was death or rehospitalization at 3 months. RESULTS: PE was confirmed in 18 of 198 patients enrolled (9.1%). The groups with and without PE were comparable with regards to demographics, the prevalence of comorbid conditions, and severity of CHF (p > 0.05). The prevalence of cancer (p = 0.0001), previous VTE (p = 0.003), and right ventricular overload (p = 0.006) was higher in the PE group. The presence of PE was also associated with a longer hospital stay (37.5 +/- 71.6 days vs 15.4 +/- 15.0 days, p = 0.001) [mean +/- SD] and a higher incidence of death or rehospitalization at 3 months (72.2% vs 43.9%, p = 0.02). In a multiple logistic regression analysis, PE remained an independent predictor of death or rehospitalization at 3 months (odds ratio, 4.0; 95% confidence interval, 1.1 to 15.1; p = 0.038). CONCLUSIONS: Acute PE commonly complicates the hospital course of patients with severe CHF, increasing the length of hospital stay and the chance of death or rehospitalization at 3 months.     

Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia

STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. METHODS: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.     

Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis

BACKGROUND: Systemic corticosteroids, antibiotics, and noninvasive positive pressure ventilation (NPPV) are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. We undertook a systematic review and metaanalysis to systematically evaluate the effectiveness of these therapies. METHODS: MEDLINE and EMBASE were searched to identify relevant randomized controlled clinical trials published from January 1968 to November 2006. We identified additional studies by searching bibliographies of retrieved articles. RESULTS: Compared with placebo, systemic corticosteroids reduced treatment failure by 46% (95% confidence interval [CI], 0.41 to 0.71), length of hospital stay by 1.4 days (95% CI, 0.7 to 2.2), and improved FEV(1) by 0.13 L after 3 days of therapy (95% CI, 0.04 to 0.21). Meanwhile, the risk of hyperglycemia significantly increased (relative risk, 5.88; 95% CI, 2.40 to 14.41). Compared with placebo, antibiotics reduced treatment failure by 46% (95% CI, 0.32 to 0.92) and in-hospital mortality by 78% (95% CI, 0.08 to 0.62). Compared with standard therapy, NPPV reduced the risk of intubation by 65% (95% CI, 0.26 to 0.47), in-hospital mortality by 55% (95% CI, 0.30 to 0.66), and the length of hospitalization by 1.9 days (95% CI, 0.0 to 3.9). CONCLUSIONS: For acute COPD exacerbations, systemic corticosteroids are effective in reducing treatment failures, while antibiotics reduce mortality and treatment failures in those requiring hospitalization and NPPV reduces the risk of intubation and in-hospital mortality, especially in those who demonstrate respiratory acidosis.     

Safety of long-acting beta-agonists in stable COPD: a systematic review

BACKGROUND: Some studies have suggested that use of long-acting beta(2)-agonists (LABAs) leads to an increased risk for adverse events in patients with stable COPD. The purpose of this review was to assess the safety, and secondarily the efficacy of LABAs. METHODS: The authors conducted a systematic review with metaanalysis of randomized clinical trials (> or = 1 month in duration) in the published literature that have compared LABAs with placebo or anticholinergics in stable poorly reversible and reversible COPD. RESULTS: MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled Trials Register were searched to identify 27 studies. LABAs reduced severe exacerbations compared with placebo (relative risk [RR], 0.78; 95% confidence interval [CI], 0.67 to 0.91). There was no significant difference between LABA and placebo groups in terms of respiratory deaths (RR, 1.09; 95% CI, 0.45 to 2.64). Use of LABAs with inhaled corticosteroids reduced the risk of respiratory death compared with LABAs alone (RR, 0.35; 95% CI, 0.14 to 0.93). Patients receiving LABAs showed significant benefits in airflow limitation measures, health-related quality of life, and use of rescue medication. Finally, tiotropium decreased the incidence of severe COPD exacerbations compared with LABAs (RR, 0.52; 95% CI, 0.31 to 0.87). CONCLUSION: This review supports the beneficial effects of the use of LABAs in patients with stable moderate-to-severe COPD, and did not confirm previous data about an increased risk for respiratory deaths. Also, our analysis suggests the superiority of tiotropium over LABAs for the treatment of stable COPD patients.     

Burden of potentially avoidable anticoagulant-associated hemorrhagic and thromboembolic events in the elderly

BACKGROUND: On average, patients receiving therapy with oral anticoagulants (OACs) in the community are in the therapeutic range only 55% of the time. Anticoagulation control strongly influences the risk of hemorrhagic and thromboembolic events in such patients. However, not all anticoagulation-associated events are attributable to poor anticoagulation control, nor do all hemorrhagic or thromboembolic events occur in anticoagulated patients. OBJECTIVE: Measure the proportion of serious hemorrhagic and thromboembolic events that would be avoided if anticoagulation control was perfect. METHODS: A retrospective cohort study of eastern Ontario using population-based administrative databases. Anticoagulation control was determined for each day of OAC exposure using linear interpolation. Incident hemorrhagic or thromboembolic hospitalizations for control and OAC patients were identified. Hemorrhages and thromboemboli in OAC patients were deemed to be avoidable if they occurred at international normalized ratios of > 3 and < 2, respectively. RESULTS: The study included > 183,000 patient-years of observation with 6,400 patient-years of OAC exposure. Anticoagulation control could be determined for 51.5% of OAC exposure time. Control patients had hemorrhagic and thromboembolic event rates of 1.8% and 1.5% per year, respectively. A total of 10,020 people were exposed to OACs, and spent 14.2% and 26.7% of the time, respectively, with excessively high and low anticoagulation intensity. Excessively high anticoagulation intensity explained 25.6% (95% confidence interval [CI], 19.4 to 31.7) and 2.0% (95% CI, 1.5 to 2.5) , respectively, of all serious hemorrhages in the anticoagulated and entire population. Excessively low anticoagulation intensity explained 11.1% (95% CI, 4.4 to 17.7) and 1.1% (95% CI, 0.7 to 1.6) of all thromboemboli, respectively. CONCLUSIONS: Our study showed that extreme anticoagulation intensity significantly impacted the health of the population. Improving anticoagulation control will have significant effects on the incidence of serious hemorrhagic and thromboembolic events in the both the anticoagulated and entire populations.     

Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD

BACKGROUND: In patients with COPD, prognosis might be determined at least in part by the extent of cardiac stress induced by hypoxia and pulmonary arterial hypertension. METHODS: B-type natriuretic peptide (BNP), a quantitative marker of cardiac stress, was determined in 208 consecutive patients presenting to the emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of BNP to predict death at a 2-year follow-up was evaluated as the primary end point. The need for intensive care and in-hospital mortality were determined as secondary end points. RESULTS: BNP levels were significantly elevated during the acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34 to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL; IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a receiver operating characteristic analysis to evaluate the potential of BNP levels to predict short-term and long-term mortality rates, areas under the curve were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to 0.66, respectively). CONCLUSIONS: In patients with AECOPD, BNP levels independently predict the need for intensive care. However, BNP levels failed to adequately predict short-term and long-term mortality rates in AECOPD patients.     

Impact of Glycoprotein IIb/IIIa Inhibition in Contemporary Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the National Cardiovascular Data Registry

ObjectivesThis study investigates the effects of glycoprotein IIb/IIIa inhibitors (GPIs) on outcomes after percutaneous coronary intervention (PCI).BackgroundIschemic complications are reduced after PCI when a GPI is added to heparin. However, there are limited data on the safety and efficacy in contemporary PCI.MethodsWe used the National Cardiovascular Data Registry CathPCI Registry data to assess the association between GPI use and PCI outcomes for acute coronary syndrome between July 2009 and September 2011. The primary outcome was all-cause in-hospital mortality. The secondary outcome was major bleeding. To adjust for potential bias, we used multivariable logistic regression, propensity-matched (PM) analysis, and instrumental variable analysis (IVA).ResultsThere were 970,865 patients included; 326,283 (33.6%) received a GPI. Unadjusted mortality and major bleeding were more common with a GPI (2.4% vs. 1.4% and 3.7% vs. 1.5%, respectively; p < 0.001 for both). In contrast, GPI use was associated with lower mortality on adjusted analyses; relative risks range from 0.72 (95% confidence interval [CI]: 0.50 to 0.97) with IVA to 0.90 (95% CI: 0.86 to 0.95) with PM. The association of GPI use with bleeding remained in adjusted analyses (multivariable relative risk: 1.93, 95% CI: 1.83 to 2.04; PM relative risk: 1.83, 95% CI: 1.74 to 1.92; and IVA relative risk: 1.53, 95% CI: 1.27 to 2.13). Subgroup analysis revealed enhanced risk reduction with ST-segment elevation myocardial infarction, high predicted mortality, and heparin-based anticoagulation.ConclusionsIn unselected acute coronary syndrome patients undergoing PCI, GPI use was associated with reduced in-hospital mortality and increased bleeding. In the modern era of PCI, there may still be a role for the judicious use of GPIs.     

Comparison of outcomes for low-risk outpatients and inpatients with pneumonia: A propensity-adjusted analysis

BACKGROUND: Low-risk patients with community-acquired pneumonia are often hospitalized despite guideline recommendations for outpatient treatment. METHODS: Using data from a randomized trial conducted in 32 emergency departments, we performed a propensity-adjusted analysis to compare 30-day mortality rates, time to the return to work and to usual activities, and patient satisfaction with care between 944 outpatients and 549 inpatients in pneumonia severity index risk classes I to III who did not have evidence of arterial oxygen desaturation, or medical or psychosocial contraindications to outpatient treatment. RESULTS: After adjusting for quintile of propensity score for outpatient treatment, which eliminated all significant differences for baseline characteristics, outpatients were more likely to return to work (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.5 to 2.6) or, for nonworkers, to usual activities (OR, 1.4; 95% CI, 1.1 to 1.8) than were inpatients. Satisfaction with the site-of-treatment decision (OR, 1.1; 95% CI, 0.7 to 1.8), with emergency department care (OR, 1.4; 95% CI, 0.9 to 1.9), and with overall medical care (OR, 1.1; 95% CI, 0.8 to 1.6) was not different between outpatients and inpatients. The overall mortality rate was higher for inpatients than outpatients (2.6% vs 0.1%, respectively; p < 0.01); the mortality rate was not different among the 242 outpatients and 242 inpatients matched by their propensity score (0.4% vs 0.8%, respectively; p = 0.99). CONCLUSIONS: After adjusting for the propensity of site of treatment, outpatient treatment was associated with a more rapid return to usual activities and to work, and with no increased risk of mortality. The higher observed mortality rate among all low-risk inpatients suggests that physician judgment is an important complement to objective risk stratification in the site-of-treatment decision for patients with pneumonia.     

Risk factors for pulmonary Aspergillus terreus infection in patients with positive culture for filamentous fungi

BACKGROUND: Invasive aspergillosis (IA) is a common fungal infection in immunocompromised patients and has a high mortality rate. Among patients with IA, Aspergillus terreus infections have become a growing concern in the past few years. OBJECTIVE: To determine the clinical risk factors for isolation of and respiratory infection by A terreus in patients with culture findings positive for filamentous fungi. METHODS: Cohort study of 505 consecutive isolates of filamentous fungi in 332 patients from one center. A terreus was present in 46 isolates from 40 patients (9.1%). Clinical histories were reviewed to identify the risk factors related to isolation of and infection by A terreus, which were grouped into three categories (ie, host factors, factors related to immunosuppression, and factors related to hospitalization), and were analyzed using a multiple logistic regression model. RESULTS: A total of 192 of 505 isolates studied (38%) were due to invasive respiratory infection. A total of 27 of 46 cultures (58.7%) that were positive for A terreus were due to invasive infection (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.37 to 4.69; p = 0.034). The factors associated with invasive A terreus infection were prophylactic use of amphotericin B aerosols (OR, 27.8; 95% CI, 6.7 to 109.7; p = 0.001) and mechanical ventilation (OR, 3.3; 95% CI, 1.02 to 10.9; p = 0.04). Transplantation was associated with a lower risk of A terreus infection (OR, 0.2; 95% CI, 0.046 to 0.789; p = 0.02). CONCLUSIONS: In patients with culture findings positive for filamentous fungi, the prophylactic use of amphotericin B aerosols and mechanical ventilation are associated with a higher risk of A terreus infections. In these patients, transplantation is associated with a lower risk of isolation and respiratory infection by A terreus.     

Ten-year cumulative incidence of COPD and risk factors for incident disease in a symptomatic cohort

STUDY OBJECTIVES: To determine the 10-year cumulative incidence of COPD in a cohort of subjects with respiratory symptoms (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) using the British Thoracic Society (BTS) and GOLD spirometric criteria. Furthermore, we sought to evaluate risk and gender factors for incident COPD. DESIGN AND SETTING: A postal questionnaire was administered in 1986 to all 6,610 subjects in eight areas of northern Sweden who had been born in 1919 to 1920 (group 1), 1934 to 1935 (group 2), and 1949 to 1950 (group 3). The response rate was 86%. All of the subjects reporting respiratory symptoms were invited to participate in a structured interview and pulmonary function test (PFT), and 1,506 (91%) participated. In 1996, 90% could be traced for follow-up, of whom 1,165 (86%) of the invited subjects participated and 1,109 subjects (534 women) were able to perform technically adequate PFTs in both 1986 and 1996. RESULTS: The 10-year cumulative incidence of COPD was estimated at 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Significant risk factors for incident COPD (using BTS and GOLD criteria) in a multivariate analysis were higher age (group 1 odds ratio [OR]: BTS criteria, 3.49; GOLD criteria, 3.37; group 2 OR: BTS criteria, 4.50; GOLD criteria, 5.70) and smoking (OR: BTS criteria, 5.37; GOLD criteria, 4.56), but not gender or heredity. Respiratory symptoms were significantly associated with incident COPD when added to the same model. In analogous analyses that were conducted separately for men and women, smoking yielded an OR of 8.52 among women (95% confidence interval [CI], 3.43 to 21.2) compared with 3.14 among men (95% CI, 1.26 to 7.84). The symptoms cough, sputum production, and chronic productive cough reached statistical significance in women, while dyspnea and wheeze did so in men. CONCLUSION: In this cohort, the 10-year cumulative incidence of COPD was 8.2% (using BTS criteria) and 13.5% (using GOLD criteria). Increasing age, smoking, and bronchitic symptoms, but not gender, were risk factors for incident COPD. GOLD stage 0 therefore appears to identify subjects who are at risk of COPD, but men and women presented different risk profiles.     

The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort study

BACKGROUND: It remains unknown whether pneumococcal bacteremia increases the risk of poor outcomes in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to investigate whether the presence of pneumococcal bacteremia influences the clinical outcomes of hospitalized patients with CAP. METHODS: We performed secondary analyses of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP and pneumococcal bacteremia, and patients with CAP and negative blood culture findings. To identify the effect of pneumococcal bacteremia on patient outcomes, we modeled all-cause mortality and CAP-related mortality using logistic regression analysis, and time to clinical stability and length of hospital stay using Cox proportional hazards models. RESULTS: We studied 125 subjects with pneumococcal bacteremic CAP and 1,847 subjects with nonbacteremic CAP. The multivariable regression analysis revealed a lack of association of pneumococcal bacteremic CAP and time to clinical stability (hazard ratio, 0.87; 95% confidence interval [CI], 0.7 to 1.1; p = 0.25), length of hospital stay (hazard ratio, 1.14; 95% CI, 0.91 to 1.43; p = 0.25), all-cause mortality (odds ratio [OR], 0.68; 95% CI, 0.36 to 1.3; p = 0.25), and CAP-related mortality (OR, 0.86; 95% CI, 0.35 to 2.06; p = 0.73). CONCLUSIONS: Pneumococcal bacteremia does not increase the risk of poor outcomes in patients with CAP. Factors related to severity of disease are confounders of the association between pneumococcal bacteremia and poor outcomes. This study indicates that the presence of pneumococcal bacteremia by itself should not be a contraindication for deescalation of therapy in clinically stable hospitalized patients with CAP.     

Is the Mortality Higher in the Pulmonary vs the Extrapulmonary ARDS?: A Metaanalysis

BACKGROUND AND AIM: ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups. METHODS: We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models. RESULTS: Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004). CONCLUSIONS: The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Predictors of survival in COPD patients with chronic hypercapnic respiratory failure receiving noninvasive home ventilation

BACKGROUND: Patients with COPD and chronic hypercapnic respiratory failure (CHRF) are at high risk, and noninvasive ventilation at home is increasingly being used. Knowledge of prognostic parameters under these conditions is limited but may be clinically helpful and highlight the role of noninvasive ventilation. METHODS: In 188 patients with COPD (mean +/- SD FEV1, 31.0 +/- 9.6% of predicted; PaCo2, 56.3 +/- 9.4 mm Hg) discharged from the hospital receiving NIV between July 1994 and July 2004, the prognostic value of body mass index (BMI), lung function, laboratory parameters, and blood gas levels was assessed by univariate and multivariate Cox regression analyses. Moreover, the impact of changes in risk factors on mortality assessed 6.7 +/- 2.8 months after the initiation of noninvasive ventilation was evaluated. RESULTS: Overall, the mortality rate during follow-up (duration, 32.2 +/- 24.3 months) was 44.7%, with 1-year, 2-year, and 5-year survival rates of 84.0%, 65.3%, and 26.4%. Deaths resulted predominantly from respiratory causes (73.8%). Univariate regression analyses revealed age, BMI, hemoglobin, FEV1, specific airway resistance, residual volume (RV)/total lung capacity (TLC), pH, and base excess (BE) to be associated with prognosis (p < 0.01 each), whereas multivariate analysis identified only age, BMI, RV/TLC, and BE as independent predictors (p < 0.05). In patients at risk (BMI < 25 km/m2, RV/TLC >or= 73%, or BE >or= 9 mmol/L), changes in these predictors were also associated with survival. CONCLUSIONS: In patients with COPD and CHRF, nutritional status, hyperinflation, and BE, which turned out to be reliable and consistent markers in CHRF, were independent prognostic factors for mortality. These data favor a multidimensional approach in these patients, including the use of noninvasive ventilation.     

Outcomes associated with combined antiplatelet and anticoagulant therapy

BACKGROUND: The use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The objective of this study was to estimate and compare the incidence of adverse and coronary event rates between patients receiving warfarin monotherapy or warfarin and antiplatelet combination therapy. METHODS: This was a retrospective, longitudinal, pharmacoepidemiologic analysis. Adult patients receiving warfarin managed by an anticoagulation service who had documented the use of antiplatelet agents (eg, aspirin, clopidogrel, and/or dipyridamole) [ie, the combination-therapy cohort] or their nonuse (ie, the monotherapy cohort) were identified as of September 30, 2005. Utilizing integrated, electronic medical records, anticoagulation-related adverse events (eg, death, hemorrhage, or thrombosis) and coronary events were identified during a 6-month follow-up period (October 2005 through March 2006). The proportions of events were compared between cohorts. Independent associations between the cohorts and the outcomes were assessed with adjustment for potential confounding factors. RESULTS: Data from 2,560 patients in the monotherapy cohort and 1,623 patients in the combination-therapy cohort were analyzed. Patients in the combination-therapy cohort were more likely to have had anticoagulation-related hemorrhages (4.2% vs 2.0%, respectively; unadjusted p < 0.001) and coronary events (0.9% vs 0.3%, respectively; p = 0.009), but not death (0.1% vs 0.2%, respectively; unadjusted p = 0.186) or thrombotic events (0.3% vs 0.4%, respectively; unadjusted p = 0.812). With adjustment, combined warfarin and antiplatelet use was independently associated with hemorrhagic events (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.44 to 5.28), but not with coronary events (OR, 0.99; 95% CI, 0.37 to 2.62). CONCLUSIONS: At the population level, the hemorrhagic risk associated with warfarin therapy combined with antiplatelet therapy appears to outweigh the benefits. These findings suggest that clinicians should carefully consider the risks and benefits when recommending combined antiplatelet therapy for patients receiving warfarin who do not meet the evidence-based criteria for such therapy.