Sleep disorders in morbid obesity.

The increasing prevalence of obesity has lead to an increase in the prevalence of sleep disordered breathing in the general population. The disproportionate structural characteristics of the pharyngeal airway and the diminished neural regulation of the pharyngeal dilating muscles during sleep predispose the obese patients to pharyngeal airway collapsibility. A subgroup of obese apneic patients is unable to compensate for the added load of obesity on the respiratory system, with resultant daytime hypercapnia. Weight loss using dietary modification and life style changes is the safest approach to reducing the severity of sleep apnea, but its efficacy is limited on the long run. Although it has inherent risks, bariatric surgery provides the most immediate result in alleviating sleep apnea. Obesity has been linked also to narcolepsy. The loss of neuropeptides co-localized in hypocretin neurons is suggested as the potential mechanism. Poor sleep quality, which leads to overall sleep loss and excessive daytime sleepiness has also become a frequent complaint in this population. Identifying abnormal nocturnal eating is critically important for patient care. Both sleep related eating disorder and night eating syndrome are treatable and represent potentially reversible forms of obesity.

Emerging therapies for obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent disorder often associated with daytime sleepiness, cognitive dysfunction, and adverse cardiovascular consequences. Available therapies are limited by either lack of long-term adherence or low response rates. Two emerging therapies hold promise in providing alternatives to patients with OSA. The first stems from the importance of the upper-airway dilator muscles in maintaining pharyngeal stability. Electrical stimulation of the genioglossus muscle improves both upper-airway diameter and ameliorates pharyngeal obstruction. The results of phase I and II clinical trials hold promise, but the reported improvements in the apnea-hypopnea index vary between subjects and concerns about long-term safety await long-term studies. The second technology relies on creating an increased expiratory nasal resistance via a bidirectional valve designed to be worn just inside the nostrils. Initial findings of clinical trials suggest reduction in severity of sleep apnea and subjective daytime sleepiness. Considerable heterogeneity in response to the nasal device was noted despite the high adherence rates. It remains unclear which patients will likely benefit a priori from these devices.

Physicians' attitudes toward guidelines for the treatment of hospitalized nursing home-acquired pneumonia.

OBJECTIVES: To assess physician awareness, attitudes, and barriers toward the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines for the treatment of hospitalized nursing home-acquired pneumonia (NHAP). METHODS: We conducted a cross-sectional survey of 522 health care providers. The survey assessed the practice setting characteristics, physicians' attitudes, and reported awareness of the 2005 ATS/IDSA guidelines. Factor analysis was conducted to identify scales of variables, and a reliability analysis was performed to verify the reliability of the identified scales. RESULTS: Three hundred and ten completed the survey. Most responders (88%) reported familiarity with the practice guidelines in their field, but less than half were familiar with the ATS/IDSA NHAP guidelines. Although attitude scores regarding clinical practice guidelines did not differ significantly among various disciplines (P = .63), there were 2 characteristics that correlated with positive attitudes toward the 2005 ATS/IDSA guidelines in a multivariate analysis: being a pulmonary specialist (P ≤ .001) and time spent on CME activity per month (P = .03). The main barriers to the 2005 ATS/IDSA guidelines implementation were lack of awareness, concerns about practicality of using the recommended regimens, increased cost, lack of documented improved outcomes, and potential conflict with other guidelines. CONCLUSION: The study indicates low levels of awareness with the 2005 ATS/IDSA guidelines for treatment of hospitalized NHAP. Targeted intervention efforts including outcome assessment and cost-effective analysis may be necessary to improve adherence with the proposed guidelines.

Tigecycline attenuates staphylococcal superantigen-induced T-cell proliferation and production of cytokines and chemokines.

The purpose of this study is to examine the in vitro modulatory effect of tigecycline on staphylococcal superantigen-induced T-cell activation and cytokines and chemokines production by human peripheral blood mononuclear cells (PBMC). Isolated human PBMC from ten healthy volunteers were stimulated by staphylococcal enterotoxin B (SEB) and Staphylococcal toxic shock syndrome toxin-1 (TSST-1) superantigens with varying concentrations of tigecycline. Cytokines IL-1 beta, IL-6, TNF-alpha, and chemokines MIP-1 alpha and MIP-1 beta concentrations were measured along with T cell proliferation. Results demonstrated that tigecycline alters cytokine production and reduces T-cell proliferation in vitro suggesting an immunomodulatory activity independent of its antimicrobial effect.

Matrix metalloproteases in bronchoalveolar lavage fluid of patients with type III Pseudomonas aeruginosa pneumonia.

OBJECTIVES: In patients with ventilator-associated pneumonia (VAP), Pseudomonas aeruginosa type III (TTSS) secreting isolates have been linked to poor clinical outcomes. Differential expression of matrix metalloproteinases (MMPs) induced by type III effector proteins may herald an irreversible lung injury. METHODS: Serial bronchoalveolar lavage fluids collected from 41 patients with P. aeruginosa at onset of VAP, day 4, and day 8 after antibiotic therapy were assayed for MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and alpha-2 macroglobulin levels. RESULTS: At the onset of VAP, isolates secreting ExoU had the highest MMP-9 levels. The response to antimicrobial therapy showed a differential drop in MMPs with significant decrease in MMP-8 and MMP-9 levels on days 4 and 8 in patients with TTSS(-) compared to TTSS(+) phenotype. The ratio of MMP-9/TIMP-1 was significantly associated with alpha-2 macroglobulin at end of therapy (r=0.4, p=0.02). Patients who survived had a lower MMP-9/TIMP-1 ratio than those who died (p=0.003). CONCLUSIONS: VAP linked to P. aeruginosa Type III phenotype portrays a divergent antibiotic treatment response in regards to the concentrations of metalloproteinases in the alveolar space. The imbalance between MMP-9 and TIMP-1 may determine the intensity of alveolocapillary damage and ultimate outcome of P. aeruginosa VAP.

Pharmacologic prevention of aspiration pneumonia: a systematic review.

BACKGROUND: Aspiration pneumonia is a common cause of morbidity and mortality. Several approaches, including bed positioning, dietary changes, and oral hygiene, have been proposed to prevent aspiration pneumonia, yet few data are available on the efficacy of pharmacologic interventions in reducing the rate of aspiration. OBJECTIVE: This study was a systematic literature review of the pharmacologic prevention of aspiration pneumonia. METHODS: We searched MEDLINE (1996-2006); EMBASE (1974-2006); Cumulative Index to Nursing & Allied Health Literature (CINAHL) (1982-2006); Health Services Technology, Administration, and Research (HealthSTAR) (1975-2006); and the Cochrane Library for relevant articles. References of all included articles were reviewed. Studies were included if they had a prospective, controlled design with a primary outcome of prevention of aspiration pneumonia. Surrogate outcomes that had a direct link to decreasing the incidence of aspiration pneumonia were considered. Selected articles were reviewed independently by 2 authors. RESULTS: Of 1108 studies reviewed, 20 were analyzed. Angiotensin-converting enzyme inhibitors may be beneficial in selected patients at high risk for aspiration. Capsaicin may be a low-risk approach to stimulate swallowing and cough reflexes. Amantadine, cabergoline, and theophylline may cause serious adverse events, and their routine use for prevention of aspiration pneumonia is not recommended. Cilostazol should not be used because of the increased risk for bleeding. CONCLUSIONS: Limited information is available on benefits and risks to guide an evidence-based approach to the pharmacologic prevention of aspiration pneumonia. Considering the high incidence of aspiration pneumonia in older adults, large randomized clinical trials on the effectiveness of pharmacologic interventions are warranted.

Effect of oral decontamination with chlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis.

INTRODUCTION: Nosocomial pneumonia is a significant cause of in-hospital morbidity and mortality. Oral care interventions have great potential to reduce the occurrence of nosocomial pneumonia. Studies using topical antiseptic agents yielded mixed results. We hypothesized that the use of chlorhexidine for oral decontamination would reduce the incidence of nosocomial pneumonia in patients requiring mechanical ventilation. METHODS: This study is a meta-analysis of randomized controlled trials assessing the effect of chlorhexidine on the incidence of nosocomial pneumonia. Data sources were Medline, EMBASE, Cochrane library, citation review of relevant primary and review articles, and contact with expert informants. Out of 1,251 articles screened, 4 randomized, controlled trials were identified that included a total of 1,202 patients. Descriptive and outcome data were extracted by two reviewers independently. Main outcome measures were the incidence of nosocomial pneumonia, and mortality. A random effects model was used. RESULTS: The incidence of nosocomial pneumonia in the control group was 7% (41 out of 615) compared to 4% (24 out of 587) in the treatment group. Gram-negative bacteria accounted for 78% of the total isolates, with Pseudomonas aeruginosa being the most frequently isolated pathogen irrespective of the intervention provided. Duration of mechanical ventilation and intensive care unit length of stay were comparable between the two groups. Overall, the use of oral decontamination with chlorhexidine did not affect the incidence of nosocomial pneumonia (odds ratio of 0.42; 95% confidence interval 0.16-1.06) or the mortality rate (odds ratio 0.77, 95% confidence interval 0.28-2.11). CONCLUSION: The use of oral decontamination with chlorhexidine did not result in significant reduction in the incidence of nosocomial pneumonia in patients who received mechanical ventilation, nor altered the mortality rate. The lack of benefit may reflect the few studies conducted in this area. Future trials should focus on a combination strategy of mechanical and pharmacological interventions.