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- Benito, Natividad, et al.
(author)
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Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.
- 2009
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In: Annals of internal medicine. - : American College of Physicians. - 1539-3704 .- 0003-4819. ; 150:9, s. 586-94
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Journal article (peer-reviewed)abstract
- The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined.To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis.Prospective cohort study.61 hospitals in 28 countries.Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005.Clinical and echocardiographic findings, microbiology, complications, and mortality.Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]).Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use.More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection.None.
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- de Groot, Kirsten, et al.
(author)
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Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis A Randomized Trial
- 2009
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In: Annals of Internal Medicine. - 0003-4819. ; 150:10, s. 3-670
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Journal article (peer-reviewed)abstract
- Background: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. Objective: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. Design: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. Setting: 42 centers in 12 European countries. Patients: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. Intervention: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. Measurement: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). Results: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). Limitations: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. Conclusion: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. Primary Funding Source: The European Union.
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- Felson, David T, et al.
(author)
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Knee buckling: prevalence, risk factors, and associated limitations in function
- 2007
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In: Annals of Internal Medicine. - 0003-4819. ; 147:8, s. 534-540
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Journal article (peer-reviewed)abstract
- BACKGROUND: Knee buckling is common in persons with advanced knee osteoarthritis and after orthopedic procedures. Its prevalence in the community is unknown. OBJECTIVE: To examine the prevalence of knee buckling in the community, its associated risk factors, and its relation to functional limitation. DESIGN: Cross-sectional, population-based study. SETTING: The Framingham Osteoarthritis Study. PARTICIPANTS: 2351 men and women age 36 to 94 years (median, 63.5 years). MEASUREMENTS: Participants were asked whether they had experienced knee buckling or "giving way" and whether it led to falling. They were also asked about knee pain and limitations in function by using the Short Form-12 and Western Ontario and McMaster Universities Osteoarthritis Index, had isometric tests of quadriceps strength, and underwent weight-bearing radiography and magnetic resonance imaging of the knee. Radiographs were scored for osteoarthritis by using the Kellgren-Lawrence scale, and magnetic resonance images were read for anterior cruciate ligament tears. The relationship of buckling to functional limitation was examined by using logistic regression that adjusted for age, sex, body mass index, and knee pain severity. RESULTS: Two hundred seventy-eight participants (11.8%) experienced at least 1 episode of knee buckling within the past 3 months; of these persons, 217 (78.1%) experienced more than 1 episode and 35 (12.6%) fell during an episode. Buckling was independently associated with the presence of knee pain and with quadriceps weakness. Over half of those with buckling had no osteoarthritis on radiography. Persons with knee buckling had worse physical function than those without buckling, even after adjustment for severity of knee pain and weakness. For example, 46.9% of participants with buckling and 21.7% of those without buckling reported limitations in their work (adjusted odds ratio, 2.0 [95% CI, 1.5 to 2.7]). LIMITATION: Causal inferences are limited because of the study's cross-sectional design. CONCLUSION: In adults, knee buckling is common and is associated with functional loss.
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- Fox, Keith A., et al.
(author)
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Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non-ST-segment elevation acute coronary syndromes
- 2007
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In: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 147:5, s. 304-310
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Journal article (peer-reviewed)abstract
- BACKGROUND: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. OBJECTIVE: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. DESIGN: Subgroup analysis of a randomized, controlled trial. SETTING: Patients presenting to the hospital with non-ST-segment elevation ACS. PATIENTS: 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. MEASUREMENTS: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. RESULTS: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. CONCLUSIONS: The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.
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- Uitterlinden, André G, et al.
(author)
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The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis
- 2006
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In: Annals of Internal Medicine. - 0003-4819. ; 145:4, s. 255-264
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Journal article (peer-reviewed)abstract
- BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear.OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures.DESIGN: Prospective multicenter large-scale association study.SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.PARTICIPANTS: 26,242 participants (18,405 women).MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures.RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model).LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis.CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
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