Sinziana Seicean

Sleep Disordered Breathing and Impaired Glucose Metabolism in Normal Weight and Overweight/Obese Individuals: The Sleep Heart Health Study

OBJECTIVE—To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus. RESEARCH DESIGN AND METHODS—Cross-sectional analysis of 2,588 participants (aged 52–96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index ≥10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference. RESULTS—SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% CI 1.1–1.6) for IFG, 1.2 (1.0–1.4) for IGT, 1.4 (1.1–2.7) for IFG plus IGT, and 1.7 (1.1–2.7) for occult diabetes. CONCLUSIONS—SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and overweight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction.

Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study.

OBJECTIVES The aim of this study was to evaluate the effect of continuous statin treatment on new-onset heart failure (HF) in patients with breast cancer receiving anthracycline-based chemotherapy. BACKGROUND In vitro and animal model experimental studies have reported that statins prevent doxorubicin-induced cardiotoxicity. METHODS A total of 628 women with newly diagnosed breast cancer (mean age 51.5 ± 10.8 years) treated with anthracycline were retrospectively identified and studied. The primary outcome (incident HF hospitalization) was compared in propensity-matched patients receiving uninterrupted statin therapy through the follow-up period of 2.55 ± 1.68 years and their counterparts not receiving continuous statin therapy. RESULTS After propensity matching (2:1), the 67 patients (10.7%) receiving uninterrupted statin therapy were combined with 134 controls. New-onset HF was observed in 67 of the 201 matched patients. Multivariate-matched Cox regression analysis showed a significantly lower hazard ratio [HR] of 0.3 (95% confidence interval [CI]: 0.1 to 0.9; p = 0.03) for patients taking uninterrupted statin therapy. Cardiotoxicity risk factors at the time of cancer diagnosis (HR: 5.0; 95% CI: 2.2 to 11.1; p < 0.001), baseline ejection fraction <55% (HR: 2.7; 95% CI: 1.2 to 6.3; p = 0.02), and trastuzumab use (HR: 3.0; 95% CI: 1.3 to 7.2; p = 0.01) were predictors of incident HF. CONCLUSIONS In this analysis of female patients with breast cancer treated with anthracycline chemotherapy, statin use was associated with a lower risk for incident HF. This finding is consistent with prior animal studies and warrants further investigation through prospective randomized clinical trials.

Cardioprotective Effect of β-Adrenoceptor Blockade in Patients With Breast Cancer Undergoing Chemotherapy Follow-Up Study of Heart Failure

Background—Chemotherapy with trastuzumab and anthracycline is associated with incident heart failure (HF) in patients with breast cancer. We hypothesized that continuous incidental use of &bgr;-blocker agents (BB) was protective against HF in patients without established structural heart disease who were receiving trastuzumab and anthracycline. Methods and Results—We identified 920 consecutive patients with breast cancer (age 52.3±11.0 years) with normal ejection fraction before receiving trastuzumab and anthracycline therapy at our institution between 2005 and 2010. Using a propensity score and a greedy 5 to 1 digit-matching algorithm, 106 of these patients on continuous BB during cancer treatment were matched with 212 patients from the same pool with similar characteristics but not on continuous BB. During a median follow-up of 3.2±2.0 years, 32 incident HF admissions were identified in these 318 patients with breast cancer, whereas 28 cancer-related (noncardiac) deaths occurred before any incident HF. Cumulative incidence regression models and cause-specific hazards of new HF events were estimated from competing risk Cox models of time-dependent covariates. Although trastuzumab therapy showed significant association with incident HF, independent of anthracycline-related cardiotoxicity (hazard ratio, 9.0; 95% confidence interval, 3.0–27.0; P<0.0001), continuous use of BB was associated with lower risk of new HF events (hazard ratio, 0.2; 95% confidence interval, 0.1–0.5; P=0.003). Conclusions—Coincidental, continuous use of BB is associated with lower incidence of HF in patients with breast cancer and normal baseline ejection fraction in a competing risk framework, and after matching for demographics, clinical, and cancer-related treatment characteristics. Prospective randomized clinical trials to validate these findings are warranted.

Cardioprotective Effect of β-Adrenoceptor Blockade in Patients With Breast Cancer Undergoing ChemotherapyClinical Perspective

Background—Chemotherapy with trastuzumab and anthracycline is associated with incident heart failure (HF) in patients with breast cancer. We hypothesized that continuous incidental use of &bgr;-blocker agents (BB) was protective against HF in patients without established structural heart disease who were receiving trastuzumab and anthracycline. Methods and Results—We identified 920 consecutive patients with breast cancer (age 52.3±11.0 years) with normal ejection fraction before receiving trastuzumab and anthracycline therapy at our institution between 2005 and 2010. Using a propensity score and a greedy 5 to 1 digit-matching algorithm, 106 of these patients on continuous BB during cancer treatment were matched with 212 patients from the same pool with similar characteristics but not on continuous BB. During a median follow-up of 3.2±2.0 years, 32 incident HF admissions were identified in these 318 patients with breast cancer, whereas 28 cancer-related (noncardiac) deaths occurred before any incident HF. Cumulative incidence regression models and cause-specific hazards of new HF events were estimated from competing risk Cox models of time-dependent covariates. Although trastuzumab therapy showed significant association with incident HF, independent of anthracycline-related cardiotoxicity (hazard ratio, 9.0; 95% confidence interval, 3.0–27.0; P<0.0001), continuous use of BB was associated with lower risk of new HF events (hazard ratio, 0.2; 95% confidence interval, 0.1–0.5; P=0.003). Conclusions—Coincidental, continuous use of BB is associated with lower incidence of HF in patients with breast cancer and normal baseline ejection fraction in a competing risk framework, and after matching for demographics, clinical, and cancer-related treatment characteristics. Prospective randomized clinical trials to validate these findings are warranted.

Airway Hyperresponsiveness in Children With Sickle Cell Anemia

BACKGROUND The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained. METHODS To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS. RESULTS Methacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1<4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P<.001), IgE (P=.009), and lactate dehydrogenase (LDH) levels (P=.005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P=.986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction. CONCLUSIONS In children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.

Obstructive Sleep Apnea and Sickle Cell Anemia

OBJECTIVE: To ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome (OSAS) in children with sickle cell anemia (SCA). METHODS: Cross-sectional baseline data were analyzed from the Sleep and Asthma Cohort Study, a multicenter prospective study designed to evaluate the contribution of sleep and breathing abnormalities to SCA-related morbidity in children ages 4 to 18 years, unselected for OSAS symptoms or asthma. Multivariable logistic regression assessed the relationships between OSAS status on the basis of overnight in-laboratory polysomnography and putative risk factors obtained from questionnaires and direct measurements. RESULTS: Participants included 243 children with a median age of 10 years; 50% were boys, 99% were of African heritage, and 95% were homozygous for βS hemoglobin. OSAS, defined by obstructive apnea hypopnea indices, was present in 100 (41%) or 25 (10%) children at cutpoints of ≥1 or ≥5, respectively. In univariate analyses, OSAS was associated with higher levels of habitual snoring, lower waking pulse oxygen saturation (Spo2), reduced lung function, less caretaker education, and non–preterm birth. Lower sleep-related Spo2 metrics were also associated with higher obstructive apnea hypopnea indices. In multivariable analyses, habitual snoring and lower waking Spo2 remained risk factors for OSAS in children with SCA. CONCLUSIONS: The prevalence of OSAS in children with SCA is higher than in the general pediatric population. Habitual snoring and lower waking Spo2 values, data easily obtained in routine care, were the strongest OSAS risk factors. Because OSAS is a treatable condition with adverse health outcomes, greater efforts are needed to screen, diagnose, and treat OSAS in this high-risk, vulnerable population.

Preoperative anemia and perioperative outcomes in patients who undergo elective spine surgery.

Study Design. Analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Objective. To assess whether preoperative anemia predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. Summary of Background Data. Prior studies have assessed the association of anemia with outcomes in various noncardiac surgical procedures. The association between preoperative anemia and 30-day outcomes for spine surgery is unknown. Methods. A total of 24,473 adults, classified as having severe (N = 88), moderate (N = 314), mild (N = 5477), and no anemia. Using propensity scores, patients with severe, mild, and moderate anemia were matched with patients with no anemia. Logistic regression was used to predict adverse postoperative outcomes. Sensitivity analyses were conducted limiting the study sample to patients who did not receive intra- or postoperative transfusion and to patients with and without preoperative cardiovascular comorbidities. Results. Patients with all levels of anemia had significantly higher risk of nearly all adverse outcomes than nonanemic patients in unadjusted and propensity-matched models. Patients with moderate and mild anemia were more likely to have prolonged length of hospitalization, experience 1 or more complications, and expire within 30 days of surgery compared with nonanemic patients. The association between anemia and adverse outcomes was found independently of intra- and postoperative transfusions, and was not more pronounced in patients with preoperative cardiovascular comorbidities. Conclusion. All levels of anemia were significantly associated with prolonged length of hospitalization and poorer operative or 30-day outcomes in patients undergoing elective spine surgery. Our findings, using a large multi-institutional sample of prospectively collected data, suggests that anemia should be regarded as an independent risk factor for perioperative and postoperative complications that deserves attention prior to elective spine surgery. Level of Evidence: 3

Impact of increased body mass index on outcomes of elective spinal surgery.

Study Design. Observational retrospective cohort study of prospectively collected database. Objective. To determine whether overweight body mass index (BMI) influences 30-day outcomes of elective spine surgery. Summary of Background Data. Obesity is prevalent in the United States, but its impact on the outcome of elective spine surgery remains controversial. Methods. We used National Surgical Quality Improvement Program, a prospective clinical database with proven validity and reproducibility consisting of 256 perioperative standardized variables from surgical patients at nearly 400 academic and nonacademic hospitals nationwide. We identified 49,314 patients who underwent elective fusion, laminectomy or both between 2006 and 2012. We divided patients according to BMI (kg/m2) as normal (18.5–24.9), preobese (25.0–29.9), obese I (30.0–34.9), obese II (35.0–39.9), and obese III (≥40). Relationship between increased BMI and outcome of surgery measured as prolonged hospitalization, complications, return to the operating room, discharged with continued care requirement, readmission, and death was determined using logistic regression before and after propensity score matching. Results. All overweight patients (BMI ≥25 kg/m2) showed increased odds of an adverse outcome compared with normal patients in unmatched analyses, with maximal effect seen in obese III group. In the propensity-matched sample, obese III patients continued to show increased odds for complications (odds ratio, 1.6; 95% confidence interval, 1.1–2.3), readmission (odds ratio, 2.3; 95% confidence interval, 1.1–4.9), and return to the operating room (odds ratio, 1.8; 95% confidence interval, 1.1–3.1). Conclusion. Impact of obesity on elective spine surgery outcome is mediated, at least in part, by comorbidities in patients with BMI between 25.0 and 39.9 kg/m2. However, BMI itself is an independent risk factor for adverse outcomes in morbidly obese patients. Level of Evidence: 3

Use and utility of preoperative hemostatic screening and patient history in adult neurosurgical patients

OBJECT The utility of preoperative hemostasis screening to predict complications is uncertain. The authors quantified the screening rate in US neurosurgery patients and evaluated the ability of abnormal test results as compared with history-based risk factors to predict hemostasis-related and general outcomes. METHODS Eleven thousand eight hundred four adult neurosurgery patients were identified in the 2006-2009 American College of Surgeons National Surgical Quality Improvement Program database. Multivariate logistic regression modeled the ability of hemostatic tests and patient history to predict outcomes, that is, intra- and postoperative red blood cell [RBC] transfusion, return to the operating room [OR], and 30-day mortality. Sensitivity analyses were conducted using patient subgroups by procedure. RESULTS Most patients underwent all 3 hemostatic tests (platelet count, prothrombin time/international normalized ratio [INR], activated partial thromboplastin time), but few had any of the outcomes of interest. The number of screening tests undergone was significantly associated with intraoperative RBC transfusion, a return to the OR, and mortality; an abnormal INR was associated with postoperative RBC transfusion. However, all tests had low sensitivity (0.09-0.2) and platelet count had low specificity (0.04-0.05). The association between patient history and each outcome was approximately the same across all tests, with higher sensitivity but lower specificity. Combining abnormal tests with patient history accounted for 50% of the mortality and 33% of each of the other outcomes. CONCLUSIONS This is the first study focused on assessing preoperative hemostasis screening as compared with patient history in a large multicenter sample of adult neurosurgery patients to predict hemostasis-related outcomes. Patient history was as predictive as laboratory testing for all outcomes, with higher sensitivity. Routine laboratory screening appears to have limited utility. Testing limited to neurosurgical patients with a positive history would save an estimated

Effect of smoking on the perioperative outcomes of patients who undergo elective spine surgery.

81,942,000 annually.