Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, ...clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression in vivo using thyroid hormone receptor (TR) β(PV/PV) knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1(-/-) and PV mice and compared tumor development, local progression, metastasis and histology in TRβ(PV/PV)/Akt1(+/+) (PVPV-Akt1WT) and TRβ(PV/PV)/Akt1(-/-) (PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (P<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (P=0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR β(PV/PV) mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model.
Hospitalizations for heart failure are associated with a high post-discharge risk for mortality. Identification of modifiable predictors of post-discharge mortality during hospitalization may improve ...outcome. Sleep disordered breathing (SDB) is the most common co-morbidity in heart failure patients.
Prospective cohort study of patients hospitalized with acute heart failure (AHF) in a single academic heart hospital. Between January 2007 and December 2010, all patients hospitalized with AHF who have left ventricular ejection fraction (LVEF) ≤ 45% and were not already diagnosed with SDB were the target population.
Patients underwent in-hospital attended polygraphy testing for SDB and were followed for a median of 3 years post-discharge. Mortality was recorded using national and state vital statistics databases.
During the study period, 1117 hospitalized AHF patients underwent successful sleep testing. Three hundred and forty-four patients (31%) had central sleep apnoea (CSA), 525(47%) patients had obstructive sleep apnoea (OSA), and 248 had no or minimal SDB (nmSDB). Of those, 1096 patients survived to discharge and were included in the mortality analysis. Central sleep apnoea was independently associated with mortality. The multivariable hazard ratio (HR) for time to death for CSA vs. nmSDB was 1.61 (95% CI: 1.1, 2.4, P = 0.02). Obstructive sleep apnoea was also independently associated with mortality with a multivariable HR vs. nmSDB of 1.53 (CI: 1.1, 2.2, P = 0.02). The Cox proportional hazards model adjusted for the following covariates: LVEF, age, BMI, sex, race, creatinine, diabetes, type of cardiomyopathy, coronary artery disease, chronic kidney disease, discharge systolic blood pressure <110, hypertension, discharge medications, initial length of stay, admission sodium, haemoglobin, and BUN.
This is the largest study to date to evaluate the effect of SDB on post-discharge mortality in patients with AHF. Newly diagnosed CSA and OSA during AHF hospitalization are independently associated with post-discharge mortality.
Abstract Background Hospitalized heart failure patients have a high readmission rate. We sought to determine the independent risk due to central sleep apnea (CSA) of readmission in patients with ...systolic heart failure (SHF). Methods and Results This was a prospective observational cohort study of hospitalized patients with SHF. Patients underwent sleep studies during their hospitalization and were followed for 6 months to determine their rate of cardiac readmissions; 784 consecutive patients were included; 165 patients had CSA and 139 had no sleep-disordered breathing (SDB); the remainder had obstructive sleep apnea (OSA). The rate ratio for 6 months' cardiac readmissions was 1.53 (95% confidence interval 1.1–2.2; P = .03) in CSA patients compared with no SDB. This rate ratio was adjusted for systolic function, type of cardiomyopathy, age, weight, sex, diabetes, coronary disease, length of stay, admission sodium, creatinine, hemoglobin, blood pressure, and discharge medications. Severe OSA was also an independent predictor of readmissions with an adjusted rate ratio of 1.49 ( P = .04). Conclusion In this first evaluation of the impact of SDB on cardiac readmissions in heart failure, CSA was an independent risk factor for 6 months' cardiac readmissions. The effect size of CSA exceeded that of all known predictors of heart failure readmissions.
CONTEXT: Recent specialty choices of graduating US medical students suggest that lifestyle may be an increasingly important factor in their career decision making. OBJECTIVE: To determine whether and ...to what degree controllable lifestyle and other specialty-related characteristics are associated with recent (1996-2002) changes in the specialty preferences of US senior medical students. DESIGN AND SETTING: Specialty preference was based on analysis of results from the National Resident Matching Program, the San Francisco Matching Program, and the American Urological Association Matching Program from 1996 to 2002. Specialty lifestyle (controllable vs uncontrollable) was classified using earlier research. Log-linear models were developed that examined specialty preference and the specialty's controllability, income, work hours, and years of graduate medical education required. MAIN OUTCOME MEASURE: Proportion of variability in specialty preference from 1996 to 2002 explained by controllable lifestyle. RESULTS: The specialty preferences of US senior medical students, as determined by the distribution of applicants across selected specialties, changed significantly from 1996 to 2002 (P<.001). In the log-linear model, controllable lifestyle explained 55% of the variability in specialty preference from 1996 to 2002 after controlling for income, work hours, and years of graduate medical education required (P<.001). CONCLUSION: Perception of controllable lifestyle accounts for most of the variability in recent changing patterns in the specialty choices of graduating US medical students.
To determine whether the preferences of female medical students are sufficient to explain the recent trend of U.S. medical students choosing specialties with controllable lifestyles.
Specialty choice ...for graduating U.S. medical students by sex was determined from the responses to the Association of American Medical Colleges' 1996-2003 Medical School Graduation Questionnaires. Using earlier research, specialties were classified as having an uncontrollable or controllable lifestyle. Log-linear models were constructed to assess the strength of association among trends in specialty choice, controllable lifestyle, and sex.
The percentage of women choosing specialties with controllable lifestyles increased from 18% in 1996 to 36% in 2003. For men, the percentage grew from 28% to 45%. The change in preference for controllable lifestyle specialties accounted for a large proportion of the variability in specialty choices for both women and men from 1996-2003 (chi2 for changes common to women and men = 920, 1 df, p < .0001). The difference between women and men in the trend toward controllable lifestyle specialties was small relative to the common changes (chi2 for differences = 12, 1 df, p = .0005).
Controllable lifestyle was strongly associated with the recent trends in specialty choice for both women and men and could not be explained solely by the specialty preferences of women.
Exercise-induced bronchospasm (EIB) occurs more commonly in elite athletes than in the general population. There have been relatively few prevalence studies examining EIB in college athletes despite ...studies which have shown significant morbidity from asthma attacks related to exercise occurring in athletes in this age group. None of the previous studies utilized eucapnic voluntary hyperpnea (EVH) testing, which is the currently recommended test to document EIB in Olympians.
Varsity athletes at The Ohio State University underwent EVH testing to assess for EIB.
One hundred seven athletes from 22 sports participated. Forty-two of 107 athletes (39%) were EIB positive according to EVH results. Thirty-six of 42 EIB-positive athletes (86%) had no prior history of EIB or asthma. There were no significant differences in the prevalence of EIB according to sex of the athlete (P=0.65) or ventilation demands of the sport (P=0.64). Symptoms were not predictive of EIB (P=0.44). The prevalence of EIB was 36% in athletes with negative symptoms and 35% for those with positive symptoms. Athletes in high-ventilation sports were significantly more symptomatic (48%) than athletes in low-ventilation sports (25%) (P=0.02); however, there was no difference in the prevalence of EIB between the two groups (P=0.64).
Varsity athletes show a high incidence of EIB when objectively diagnosed by a variety of pulmonary function criteria. Sex of the athlete or ventilation demands of the sport does not affect the prevalence of EIB. The use of symptoms to diagnose EIB is not predictive of whether athletes have objectively documented EIB. Empiric diagnosis and treatment of EIB on the basis of subjective symptoms alone may lead to an increased number of inaccurate diagnoses and increased morbidity.
Despite anecdotal evidence of a possibility of decreased effectiveness of oral contraceptives (OCs) with some antibiotics, it is not known whether antibiotic use in dermatologic practices engenders ...any increased risk of accidental pregnancy.
Our purpose was to examine the effect of commonly prescribed oral antibiotics (tetracyclines, penicillins, cephalosporins) on the failure rate of OCs.
The records from three dermatology practices were reviewed, and 356 patients with a history of combined oral antibiotic/OC use were surveyed retrospectively. Of these patients, 263 also provided “control” data (during the times they used OCs alone). An additional 162 patients provided control data only.
Five pregnancies occurred in 311 woman-years of combined antibiotic/OC exposure (1.6% per year failure rate) compared with 12 pregnancies in 1245 woman-years of exposure (0.96% per year) for the 425 control patients. This difference was not significant (
p = 0.4) and the 95% confidence interval on the difference (−0.81, 2.1) ruled out a substantial difference (> 2.1 % per year). There was also no significant difference between OC failure rates for the women who provided data under both conditions, nor between the two control groups. All our data groups had failure rates below the 3% or higher per year, which are typically found in the United States.
The difference in failure rates of OCs when taken concurrently with antibiotics commonly used in dermatology versus OC use alone suggests that these antibiotics do not increase the risk of pregnancy. Physicians and patients need to recognize that the expected OC failure rate, regardless of antibiotic use, is at least 1% per year and it is not yet possible to predict in whom OCs may fail.
Background: Treatment of obstructive sleep apnea (OSA) in outpatients with systolic heart failure improves cardiac function. We evaluated
the impact of immediate inpatient diagnosis and treatment of ...OSA in hospitalized patients with acutely decompensated heart
failure (ADHF) on in-hospital cardiac outcomes.
Methods: A pilot randomized controlled trial was conducted in an academic heart hospital. Patients with ADHF underwent an attended
in-hospital sleep study within 2 days of hospital admission to establish the diagnosis of sleep-disordered breathing. The
participants were 46 consecutive patients with ADHF who had OSA (apnea-hypopnea index AHI, ⥠15 events per hour). Participants
were randomly assigned to either the intervention arm (n = 23), with in-hospital treatment of OSA using auto-adjusting positive
airway pressure along with standard treatment of ADHF, or to the control arm (n = 23), in which they received only standard
treatment for ADHF. The primary outcome was the change in left ventricular ejection fraction (LVEF) 3 nights postrandomization.
Results: The change in LVEF from baseline to 3 days postrandomization in the intervention arm was significantly superior to that of
the control group. The difference in LVEF improvement was 4.6% (p = 0.03). LVEF increased in the intervention group by 4.5%
(SE, 1.7%). The LVEF change in the control arm was â 0.3% (SE, 1.5%). The difference in LVEF improvement between the two groups
persisted after adjustment for baseline LVEF, type of cardiomyopathy, BMI, AHI, and sex.
Conclusions: An approach of early identification and in-hospital treatment of OSA in patients with ADHF is feasible and resulted in improvement
in systolic function. The impact of this approach on out-of-hospital outcomes requires further investigation.
Trial registration: ClinicalTrials.gov Identifier: NCT00701038
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