Marie Diener-West

Prospective Study of Obstructive Sleep Apnea and Incident Coronary Heart Disease and Heart Failure The Sleep Heart Health Study

Background— Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women. Methods and Results— A total of 1927 men and 2495 women ≥40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men ≤70 years of age (adjusted hazard ratio 1.10 [95% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of any age. Among men 40 to 70 years old, those with AHI ≥30 were 68% more likely to develop coronary heart disease than those with AHI <5. Obstructive sleep apnea predicted incident heart failure in men but not in women (adjusted hazard ratio 1.13 [95% confidence interval 1.02 to 1.26] per 10-unit increase in AHI). Men with AHI ≥30 were 58% more likely to develop heart failure than those with AHI <5. Conclusions— Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal.

Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.

RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

Double-Blind Placebo-Controlled Trial of Fluconazole to Prevent Candidal Infections in Critically Ill Surgical Patients

ObjectiveTo evaluate the prophylactic use of enteral fluconazole to prevent invasive candidal infections in critically ill surgical patients. Summary Background DataInvasive fungal infections are increasingly common in the critically ill, especially in surgical patients. Although fungal prophylaxis has been proven effective in certain high-risk patients such as bone marrow transplant patients, few studies have focused on surgical patients and prevention of fungal infection. MethodsThe authors conducted a prospective, randomized, placebo-controlled trial in a single-center, tertiary care surgical intensive care unit (ICU). A total of 260 critically ill surgical patients with a length of ICU stay of at least 3 days were randomly assigned to receive either enteral fluconazole 400 mg or placebo per day during their stay in the surgical ICU at Johns Hopkins Hospital. ResultsThe primary end point was the time to occurrence of fungal infection during the surgical ICU stay, with planned secondary analysis of patients “on-therapy” and alternate definitions of fungal infections. In a time-to-event analysis, the risk of candidal infection in patients receiving fluconazole was significantly less than the risk in patients receiving placebo. After adjusting for potentially confounding effects of the Acute Physiology and Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal colonization at enrollment, the risk of fungal infection was reduced by 55% in the fluconazole group. No difference in death rate was observed between patients receiving fluconazole and those receiving placebo. ConclusionsEnteral fluconazole safely and effectively decreased the incidence of fungal infections in high-risk, critically ill surgical patients.

Clinical Information Technologies and Inpatient Outcomes: A Multiple Hospital Study

BACKGROUND Despite speculation that clinical information technologies will improve clinical and financial outcomes, few studies have examined this relationship in a large number of hospitals. METHODS We conducted a cross-sectional study of urban hospitals in Texas using the Clinical Information Technology Assessment Tool, which measures a hospitals level of automation based on physician interactions with the information system. After adjustment for potential confounders, we examined whether greater automation of hospital information was associated with reduced rates of inpatient mortality, complications, costs, and length of stay for 167 233 patients older than 50 years admitted to responding hospitals between December 1, 2005, and May 30, 2006. RESULTS We received a sufficient number of responses from 41 of 72 hospitals (58%). For all medical conditions studied, a 10-point increase in the automation of notes and records was associated with a 15% decrease in the adjusted odds of fatal hospitalizations (0.85; 95% confidence interval, 0.74-0.97). Higher scores in order entry were associated with 9% and 55% decreases in the adjusted odds of death for myocardial infarction and coronary artery bypass graft procedures, respectively. For all causes of hospitalization, higher scores in decision support were associated with a 16% decrease in the adjusted odds of complications (0.84; 95% confidence interval, 0.79-0.90). Higher scores on test results, order entry, and decision support were associated with lower costs for all hospital admissions (-

Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis.

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Reproducibility of the diagnosis of endometrial hyperplasia, atypical hyperplasia, and well-differentiated carcinoma

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Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women

538, respectively; P < .05). CONCLUSION Hospitals with automated notes and records, order entry, and clinical decision support had fewer complications, lower mortality rates, and lower costs.

Identification of an optimal subgroup for treatment evaluation of patients with brain metastases using rtog study 7916

RATIONALE The prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV(1) decline in CF is unknown. OBJECTIVES To determine the association between MRSA respiratory infection and FEV(1) decline in children and adults with CF. METHODS This was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996-2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV(1) decline, adjusted for confounders, in individuals aged 8-21 years and adults (aged 22-45 yr). Two different statistical models were used to assess robustness of results. MEASUREMENTS AND MAIN RESULTS The study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (> or =3 MRSA cultures; average, 6.8 positive cultures) and were subsequently followed for an average of 3.5 years. Even after adjustment for confounders, rate of FEV(1) decline in individuals aged 8-21 years with persistent MRSA was more rapid in both statistical models. Their average FEV(1) decline of 2.06% predicted/year was 43% more rapid than the 1.44% predicted/year in those without MRSA (difference, -0.62% predicted/yr; 95% confidence interval, -0.70 to -0.54; P < 0.001). Effect of MRSA on FEV(1) decline in adults was not clinically significant. CONCLUSIONS Persistent infection with MRSA in individuals with CF between the ages of 8 and 21 years is associated with a more rapid rate of decline in lung function.

Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial

Many studies have attempted to identify histologic features that aid in the distinction of atypical hyperplasia (AH) from hyperplasia without atypia and well-differentiated endometrioid carcinoma, but few have evaluated the reproducibility of these diagnoses. Five pathologists independently reviewed 100 endometrial biopsy and curettage specimens chosen to represent the entire spectrum of proliferative lesions of the endometrium, including proliferative endometrium (PEM), hyperplasia without atypia, AH, and well-differentiated endometrioid carcinoma. Slides were reviewed twice for diagnosis, with an intervening evaluation of a checklist of histologic features. Intraobserver and interobserver agreement were assessed using the kappa statistic. Intraobserver kappa values ranged from 0.67 to 0.89 (76% to 89% agreement). Interobserver kappa values by diagnostic category were: proliferative endometrium: 0.86; hyperplasia without atypia: 0.60; AH: 0.47; well-differentiated endometrioid carcinoma: 0.83; with a kappa value of 0.69 for all cases combined. Associations between the selected histologic features and the given diagnoses for each pathologist were analyzed using multiple logistic regressions to identify features that were useful for distinguishing among diagnostic categories. Histologic features determined by univariable and multivariable analyses that were found to be most associated with distinguishing diagnostic categories were: proliferative endometrium versus hyperplasia without atypia: gland crowding (univariable, multivariable), and gland branching (univariable); hyperplasia without atypia versus AH: presence of nucleoli (univariable, multivariable), nuclear enlargement (univariable), vesicular chromatin change (univariable), nuclear pleomorphism (univariable), chromatin irregularities (univariable), and loss of polarity (univariable); hyperplasia without atypia versus carcinoma: glandular confluence/complex cribriform pattern (univariable, multivariable), stromal alteration (univariable, multivariable), and necrosis (univariable). In summary, interobserver agreement was good but was lowest for AH. Only the presence of nucleoli was strongly associated with distinction of AH from hyperplasia without atypia. Individual pathologists use additional features to diagnose atypia, but these features are not consistently associated with that diagnosis. Cribriform architectural pattern and stromal alteration were associated with the distinction of well-differentiated endometrioid carcinoma from AH.

Clinical and Pathologic Predictors of Survival in Patients With Thymoma

SummaryWomen with pseudomyxoma peritonei (PMP), characterized by multifocal mucinous implants (disseminated peritoneal adenomucinosis), often have synchronous appendiceal and ovarian mucinous tumors. There has been considerable debate as to whether the ovarian tumors are secondary to the appendiceal tumor or are independent primary ovarian tumors; the latter are usually classified as mucinous tumors of low malignant potential (MLMP). It has been reported that cytokeratins (CK) 7, 18, and 20, carcinoembryonic antigen (CEA). and human alveolar macrophage 56 (HAM-56) are useful markers for distinguishing primary ovarian neoplasms from metastases of intestinal origin. Nearly all primary ovarian MLMP tumors and mucinous carcinomas are positive for CK 7, 18, and 20, CEA, and HAM-56, whereas most colorectal adenocarcinomas are negative for both CK 7 and HAM-56 and positive for CK 20 and CEA. Thirteen appendiceal and 14 ovarian mucinous tumors from 14 cases of PMP and 11 primary ovarian MLMP tumors were studied immunohistochemically for expression of CK 7, 18, and 20, monoclonal and polyclonal CEA (mCEA and pCEA). and HAM-56. Of 14 cases of PMP, 10 (71.4%) had identical staining patterns for all antibodies in both the appendiceal and ovarian tumors. For eight of these, the pattern of immunoreactivity was characterized by negative reactions for CK 7 and HAM-56 and positive reactions for CK 18 and 20. mCEA, and pCEA. One additional case for which only the ovarian tumor could be stained had the same pattern. The remaining two cases were also positive for CK 18 and 20 and CEA. but in addition were positive for CK 7. Two cases were discordant only for CK 7 and one case was discordant for both CK 7 and HAM-56. All 11 MLMP tumors were positive for CK 7 and 18, and pCEA. Eight (72.7%) of 11 were positive for HAM-56, mCEA, and CK 20. There was a statistically significant difference in the frequency of immunoreactivity for CK 7 (p = 0.0005) and HAM-56 (p = 0.0002) between the ovarian mucinous tumors in PMP and the MLMP tumors, with the ovarian tumors in PMP tending to be negative for CK 7 and HAM-56. similar to the appendiceal adenomas. Most ovarian mucinous tumors in PMP demonstrate a pattern of immunoreactivity with CK 7, 18, and 20, CEA, and HAM-56 that is identical to the associated appendiceal adenoma and distinct from primary ovarian MLMP tumors, consistent with the interpretation that these ovarian tumors are secondary to the appendiceal tumor.