Guidelines for Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is common, costly, and clinically serious. Several national and international practice guidelines have been developed to promote more appropriate, cost-effective care for patients with CAP. This article compares and contrasts eight international practice guidelines for the management of CAP, describes the extent to which recommendations are reflected in practice, and proposes explanations for non-adherence to guidelines. We found consistency in recommendations across all the guidelines for the management of patients with CAP requiring intensive care. In this setting, all guidelines recommend chest radiography, sputum Gram stain and culture, blood cultures, testing for Legionella pneumophila, and timely administration of antibiotics active against both typical (i.e. Streptococcus pneumoniae, Hemophilus influenzae) and atypical organisms (i.e. Legionella spp., Mycoplasma pneumoniae, and Chlamydia pneumoniae). Recommendations for the management of the average inpatient with pneumonia were more variable, with the greatest differences between the North American and European guidelines. The North American guidelines (in contrast to European ones), recommended empiric treatment of typical and atypical organisms in all inpatients. There were also differences in policies regarding the necessity of chest radiography, sputum studies, and serologic testing. Some guidelines explicitly embrace the use of prediction rules to inform the decision to hospitalize, while others do not. Some of these admission decision algorithms focus on identifying low risk patients, while others are most concerned with high risk patients. There was also considerable variation in the specificity and operationalization of clinical criteria for switching from parenteral to oral antibiotics or judging appropriateness for discharge. Many recommendations for key management decisions tended to lack explicit, objective, and actionable criteria that could be easily implemented in real world practice. Review of the pneumonia literature revealed that physician performance of guideline-recommended best practices is often suboptimal. Administration of timely antibiotics (< or =8 hours of presentation) and use of first-line antibiotics occurred in 75-85% and 18-79% of cases, respectively. Collection of blood cultures within 24 hours of presentation and prior to administration of antibiotics was achieved in 69-83% and 63-82% of cases, respectively. Screening the eligibility of CAP patients for hospital-based pneumococcal and influenza vaccination occurred on average in 11 and 14% of hospitalizations, respectively, in the US. Lack of awareness of guidelines, conflicting advice among them, and lack of specific, objective, actionable recommendations most likely contribute to nonadherence to CAP guidelines. Increased attention to these factors will be needed if professional society practice guidelines are to fulfill their promise as tools for improving the quality and outcomes of care for patients with pneumonia.     

Physical therapy and mobility 2 and 6 months after hip fracture

OBJECTIVES: To examine the relationship between early physical therapy (PT), later therapy, and mobility 2 and 6 months after hip fracture. DESIGN: Prospective, multisite observational study. SETTING: Four hospitals in the New York City area. PARTICIPANTS: Four hundred forty-three hospitalized older patients discharged after surgery for hip fracture in 1997-98. MEASUREMENTS: Patient demographics, fracture type, comorbidities, dementia, number of new impairments at discharge, amount of PT between day of surgery and postoperative day (POD) 3, amount of therapy between POD4 and 8 weeks later, and prefracture, 2-, and 6-month mobility measured using the Functional Independence Measure. RESULTS: More PT immediately after hip fracture surgery was associated with significantly better locomotion 2 months later. Each additional session from the day of surgery through POD3 was associated with an increase of 0.4 points (P=.032) on the 14-point locomotion scale, but the positive relationship between early PT and mobility was attenuated by 6 months postfracture. There was no association between later therapy and 2- or 6-month mobility. CONCLUSION: PT immediately after hip fracture surgery is beneficial. The effects of later therapy on mobility were difficult to assess because of limitations of the data. Well-designed randomized, controlled trials of the effect of varying schedules and amounts of therapy on functional status after hip fracture would be informative.     

Effects of statins on vascular structure and function: a systematic review

PURPOSE: Statins reduce cardiovascular events by more than can be explained by their effects on lipids. We conducted a systematic review of how statins affect vascular structure and function, differences among statins, and correlations between the effects of statins on vascular outcomes and either lipid levels or cardiovascular outcomes. METHODS: We primarily searched MEDLINE (1980 to March 2004) to identify all studies with at least 10 subjects that reported the effects of currently available statins on coronary artery stenosis, carotid intima-media thickness, and endothelial function (excluding studies of drug combinations and subjects with organ transplants). Meta-analyses were performed when feasible. RESULTS: Statins decrease the progression and increase the regression of coronary artery lesions and luminal narrowing. Compared with placebo, statins decrease the likelihood of coronary artery restenosis (summary risk ratio = 0.85; 95% confidence interval: 0.77 to 0.95). Statins appear to slow the progression of carotid artery intima-media thickness. Although the effect of statins on coronary endothelial function is uncertain, statins appear to improve peripheral endothelial function. There is no conclusive evidence to suggest that individual statins differ in their effects on these outcomes. Studies generally found weak or no correlation between the effects of statins on vascular outcomes and lipid levels. No study showed a correlation between vascular effect and clinical outcome. CONCLUSION: Statins slow the progression of, and may reverse, atherosclerosis. The magnitude of these effects, however, is small compared with the effects of statins on cardiovascular events. Statins also improve measures of vascular function, which may contribute to their clinical benefits. There is insufficient evidence to suggest that individual statins differ in their vascular effects.     

Markers of Increased Cardiovascular Risk in Postmenopausal Women: Focus on Oxidized-LDL and HDL Subpopulations

Objective. To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers. Methods. 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF-α), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1). Results. Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF-α and reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF-α and total, large, and small HDL-c, LDL-c, and Ox-LDL. Conclusions. Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.     

Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis?

Chronic hepatitis C virus (HCV) infection is a well-recognized risk factor for hepatocellular carcinoma (HCC). As a co-risk factor, the role of tobacco use in HCV-driven carcinogenesis and relevant underlying mechanisms remain largely unclear. The latest discoveries about HCV replication have shown that HCV RNA hijacks cellular miRNA-122 by forming an Ago2-HCV-miR-122 complex that stabilizes the HCV genome and enhances HCV replication. Our previous work has demonstrated that aqueous tobacco smoke extract (TSE) is a potent activator of HIV replication via TSE-mediated viral protection from oxidative stress and activation of a set of genes that can promote viral replication. Since HCV is, like HIV, an enveloped virus that should be equally susceptible to lipid peroxidation, and since one of the TSE-upregulated genes, the DDX3 helicase, is known to facilitate HCV replication, we hypothesize that (1) tobacco use can similarly enhance HCV viability and replication, and promote HCC progression by up-regulation of DDX3, and (2) by competing for binding with miR-122 as a competing endogenous RNA (ceRNA), HCV replication can liberate miR-122’s direct target, oncogenic gene cyclin G1 (CCNG1); furthermore, simultaneous tobacco use can synergistically enhance this competing effect via HCV upregulation. Our hypotheses may lay a foundation for better understanding of carcinogenesis in HCV-driven HCC and the potential role of tobacco as a cofactor. Disrupting the HCV ceRNA effect may provide a new strategy for designing anti HCV/HCC drugs.