Citations

The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6‐year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C‐11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C‐11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI‐like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD.

As medical providers seek new ways to control costs, online visits have begun to receive serious consideration. The purpose of this study was to compare the odds of being a cost outlier during a 6-month period after either an online visit or a standard drop-in visit in a conventional medical office setting. Medical records of primary care patients (both adults and children) seen in a large group practice in Minnesota in 2008 were analyzed for this study. Two groups of patients were studied: those who had an online visit ( N = 390) and a comparison group who had regular office care for same-day, acute visits ( N = 376). Case types were classified as either complex or common, with common being defined as treatment for pinkeye, sore throat, viral illness, bronchitis, or cough. Outliers were defined as patients for whom standard costs exceeded the 75 th percentile during a 6-month period after the index visit. Multiple logistic regression analysis was used to adjust for differences between groups. The percentage of online visitors who were cost outliers was 21.2 (versus 28.5 in the standard visit group). Median standard costs were $161 for online visits and $219 for same-day acute visits. The adjusted odds of being a cost outlier was lower for the online visit group than for the standard visit group (odds ratio [OR] 0.52, 95% confidence interval [95% CI] 0.35–0.77) after adjusting for number of visits in the previous 6 months, age, sex, and case type. Outpatient visits in the previous 6 months were positively related to outlier status (OR 1.23, 95% CI 1.17–1.29). Online visits appeared to reduce medical costs for patients during a 6-month period after the visit. ( Population Health Management 2010;13:59–63)

OBJECTIVE:No study has evaluated the association between state endorsement of American Academy of Pediatrics (AAP) and American Public Health Association (APHA) national guidelines and unnecessary exclusion decisions. We sought to determine the rate of unnecessary exclusion decisions by child care directors in a state that endorses AAP/APHA guidelines and to identify factors that are associated with higher unnecessary exclusion decisions.METHODS:A telephone survey was administered to directors in metropolitan Milwaukee, Wisconsin. Directors were randomly sampled from a list of 971 registered centers. Director, center, and neighborhood characteristics were obtained. Directors reported whether immediate exclusion was indicated for 5 vignettes that featured children with mild illness that do not require exclusion by AAP/APHA guidelines. Weighted data were summarized by using descriptive statistics. Regression analysis was used to identify factors that were associated with directors' exclusion decisions.RESULTS:A total of 305 directors completed the survey. Overall, directors would unnecessarily exclude 57% of children. More than 62% had never heard of the AAP/APHA guidelines. Regression analysis showed fewer exclusions among more experienced compared with less experienced directors, among larger centers compared with smaller centers, and among centers that were located in areas with a higher percentage of female heads of household. Centers with ≤10% children on state-assisted tuition excluded more.CONCLUSIONS:High rates of inappropriate exclusion persist despite state endorsement of AAP/APHA guidelines. Focused initial and ongoing training of directors regarding AAP/APHA guidelines may help to reduce high rates of unnecessary exclusions.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Abstract Background: There is strong and consistent evidence that a genetic component contributes to the etiology of chronic lymphocytic leukemia (CLL). A recent genome-wide association study of CLL identified seven genetic variants that increased the risk of CLL within a European population. Methods: We evaluated the association of these variants, or variants in linkage disequilibrium with these variants, with CLL risk in an independent sample of 438 CLL cases and 328 controls. Results: Of these seven single nucleotide polymorphisms (SNP), six had P trend < 0.05 and had estimated odds ratios (OR) that were strikingly comparable to those of the previous study. Associations were seen for rs9378805 [OR, 1.47; 95% confidence intervals (CI), 1.19-1.80; P trend = 0.0003] near IRF4 and rs735665 near GRAMD1B (OR, 1.47; 95% CI, 1.14-1.89; P trend = 0.003). However, no associations (P > 0.05) were found for rs11083846, nor were any found for any SNP in linkage disequilibrium with rs11083846. Conclusions: Our results confirm the previous findings and further support the role of a genetic basis in the etiology of CLL; however, more research is needed to elucidate the causal SNP(s) and the potential manner in which these SNPs or linked SNPs function in CLL pathogenesis. Cancer Epidemiol Biomarkers Prev; 19(4); 1098–102. ©2010 AACR.

Abstract Aromatase inhibitors play a prominent role in the management of postmenopausal women with endocrine-sensitive breast cancer, but there is large variability in both efficacy and tolerability. The purpose of our study was to define interindividual variation in anastrozole metabolism and pharmacodynamics among patients treated with the approved daily dose of 1 mg in a standard practice setting as adjuvant therapy for resected early breast cancer. This study was performed in 191 women in whom pretreatment and during anastrozole plasma concentrations of estrone (E1), estradiol (E2), estrone conjugates, androstenedione, and testosterone were determined and correlated with plasma concentrations of anastrozole and anastrozole metabolites. There were large interindividual variations in plasma anastrozole and anastrozole metabolite concentrations, as well as pretreatment and postdrug plasma E1, E2, and E1 conjugate and estrogen precursor (androstenedione and testosterone) concentrations. E1 and E2 concentrations were below the lower limit of quantitation (LLQ) in most patients after anastrozole therapy (83% for both), but those with detectable concentrations had a broad range (1.58–45.2 and 0.635–97.0 pg/mL, respectively). E1 conjugates after anastrozole therapy were above the LLQ in most patients (93%), with wide interpatient variability (3.50–2,990 pg/mL). Two patients seemed to extensively metabolize anastrozole and failed to display substantial decreases in estrogens. Acknowledging the potential factor of variable compliance, our results showed large interindividual variation in anastrozole metabolism and its effect on circulating estrogens in postmenopausal patients. These findings may have implications with regard to efficacy and adverse events and may indicate the need to “individualize” therapy with this drug. Cancer Res; 70(8); 3278–86. ©2010 AACR.

A collaborative care model (CCM) has been implemented for management of depression. This paper studies the impact that the CCM had on cost measures for the period of six months after initial diagnosis of depression compared to patients receiving usual care (UC). There was a significant increase in the CPT costs for the six months following diagnosis in the CCM group ($451.35 vs. $323.50, P < 0.001). The average CPT cost rank and CPT cost differential were also significantly increased in the CCM group. The adjusted means of the CPT costs were (when controlling for prior utilization) $452.11 for the CCM group and $322.09 for UC (P < 0.001). In the CCM group; there were 161 patients (73.5%) that achieved a clinical response for their depression compared to the UC group, which had a 15.1% (18/119) response rate (P < 0.001). There also was a significant difference between the groups in those who were symptoms free of their depression (PHQ-9 score < 5), with the CCM having 59.4% of the patients symptom-free compared to 10.9% of the UC group (P < 0.001). In this group of patients, CCM is associated with markedly improved clinical outcomes for depression, however with a modest short-term increase in CPT costs.

Major basic protein (MBP) released from activated eosinophils may influence airway hyperresponsiveness (AHR) by either direct effects on airway myocytes or by an indirect effect. In this study, human bronchi, freshly isolated human eosinophils, or MBP purified from human eosinophil granules were incubated for studying eosinophil infiltration and MBP localization. Eosinophils immediately adhered to intact human airway as well as to cultured human airway myocytes and epithelium. Following incubation 18–24 h, eosinophils migrated into the airway media, including the smooth muscle layer, but had no specific recruitment to airway neurons. Eosinophils released significant amounts of MBP within the airway media, including areas comprising the smooth muscle layer. Most deposits of MBP were focally discrete and restricted by immunologic detection to a maximum volume of∼300 μm3about the eosinophil. Native MBP applied exogenously was immediately deposited on the surface of the airway, but required at least 1 h to become detected within the media of the airway wall. Tissue MBP infiltration and deposition increased in a time- and concentration-dependent manner. Taken together, these findings suggest that eosinophil-derived cationic proteins may alter airway hyperresponsiveness (AHR) in vivo by an effect that is not limited to the bronchial epithelium.