Gene-based aggregate SNP associations between candidate AD genes and cognitive decline.

Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD-associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions. In two single-sex cohorts of older, community-dwelling adults, we examined the association between SNPs in previously implicated gene regions and cognitive decline (age-adjusted person-specific cognitive slopes) using a Sequence Kernel Association Test (SKAT). In regions which showed aggregate significance, we examined the univariate association between individual SNPs in the region and cognitive decline. Only two of the original AD-associated SNPs were significantly associated with cognitive decline in our cohorts. We identified significant aggregate-level associations between cognitive decline and the gene regions BIN1, CD33, CELF1, CR1, HLA cluster, and MEF2C in the all-female cohort and significant associations with ABCA7, HLA cluster, MS4A6E, PICALM, PTK2B, SLC24A4, and SORL1 in the all-male cohort. We also identified a block of eight correlated SNPs in CD33 and several blocks of correlated SNPs in CELF1 that were significantly associated with cognitive decline in univariate analysis in the all-female cohort.

Memory complaints and risk of cognitive impairment after nearly 2 decades among older women.

OBJECTIVES: To investigate the association between subjective memory complaints (SMCs) and long-term risk of cognitive impairment in aging because most previous studies have followed individuals for only a few years. METHODS: Participants were 1,107 cognitively normal, community-dwelling older women (aged 65 years and older at baseline) in a prospective study of aging. SMCs were assessed shortly after baseline and repeatedly over time with the yes/no question, "Do you feel you have more problems with memory than most?" Cognitive status 18 years later (normal or impaired with mild cognitive impairment or dementia) was determined by an expert panel. Using logistic regression, we investigated the association between SMCs over time and risk of cognitive impairment, adjusting for demographics, baseline cognition, and characteristics that differed between those with and without SMCs. RESULTS: At baseline, 8.0% of participants (n = 89) endorsed SMCs. Baseline SMCs were associated with increased risk of cognitive impairment 18 years later (adjusted odds ratio [OR] = 1.7, 95% confidence interval 1.1-2.8). Results were unchanged after excluding participants with depression. The association between SMCs and cognitive impairment was greatest at the last SMC assessment time point (18 years before diagnosis: adjusted OR = 1.7 [1.1-2.9]; 14 years before diagnosis: adjusted OR = 1.6 [0.9-2.7]; 10 years before diagnosis: adjusted OR = 1.9 [1.1-3.1]; 4 years before diagnosis: adjusted OR = 3.0 [1.8-5.0]). CONCLUSIONS: SMCs are associated with cognitive impairment nearly 2 decades later among older women. SMCs may be a very early symptom of an insidious neurodegenerative disease process, such as Alzheimer disease.

Do Family Responsibilities and a Clinical Versus Research Faculty Position Affect Satisfaction with Career and Work-Life Balance for Medical School Faculty?

BACKGROUND: Balancing career and family obligations poses challenges to medical school faculty and contributes to dissatisfaction and attrition from academics. We examined the relationship between family setting and responsibilities, rank, and career and work-life satisfaction for faculty in a large U.S. medical school. METHODS: Baseline faculty surveys were analyzed from the first year of a 4-year National Institutes of Health-funded study to evaluate awareness, knowledge, attitudes, and use of family friendly policies and career satisfaction. The study focus was on the impact of family responsibilities and characteristics of the faculty position (rank, clinical vs. nonclinical, and academic series) in multivariate comparisons between primary predictors and outcomes of interest. RESULTS: Both clinical and family responsibilities for children under 18 play a major and interacting role in satisfaction with career and work-life balance. Clinical faculty respondents without children at home reported significantly greater career satisfaction and better work-life balance than their nonclinical counterparts. Nonclinical faculty respondents with children reported greater satisfaction and better balance than counterparts without family responsibilities. However, the advantage in career satisfaction and work-life balance for clinical faculty respondents disappeared for those with responsibility for young children. No gender-based differences were noted in the results or across faculty rank for respondents; however, for women, reaching associate professor resulted in greater career satisfaction. CONCLUSION: This study suggests that both work-related factors and family responsibilities influence satisfaction with career and work-life balance, but the predictors appear to interact in complex and nuanced ways. Further research is needed to delineate more clearly these interactions and to explore other factors that may play important additional roles.

Sleep Quality and Risk of Dementia Among Older Male Veterans.

OBJECTIVE: To determine whether a diagnosis of sleep disturbance is associated with dementia in older veterans. METHODS: For this retrospective cohort study, we obtained medical record data from the Department of Veterans Affairs National Patient Care Database for 200,000 randomly selected veterans aged 55 years and older. Prevalent cases of dementia from the baseline period (2000-2003) were excluded, leaving an analytic sample of 179,738 male veterans. Follow-up took place from 2004 to 2011. The primary outcome was all-cause dementia, ascertained using International Classification of Disease, Ninth Revision codes. Sleep disturbance, the primary predictor, was also ascertained using these codes. RESULTS: After adjusting for potential confounders, those with sleep disturbance had a 27% increased risk of dementia (hazard ratio: 1.27; 95% confidence interval: 1.20-1.34). CONCLUSION: Sleep disturbance was associated with increased risk of dementia among a large cohort of older, primarily male veterans.

Traumatic brain injury in later life increases risk for Parkinson disease.

OBJECTIVE: Traumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We sought to address these concerns by quantifying risk of PD after TBI compared to non-TBI trauma (NTT; defined as fractures). METHODS: Using inpatient/emergency department (ED) International Classification of Disease, Ninth Revision code data for California hospitals from 2005-2006, we identified patients aged ≥55 years with TBI (n = 52,393) or NTT (n = 113,406) and without baseline PD or dementia who survived hospitalization. Using Kaplan-Meier estimates and Cox proportional hazards models (adjusted for age, sex, race/ethnicity, income, comorbidities, health care use, and trauma severity), we estimated risk of PD after TBI during follow-up ending in 2011. We also assessed interaction with mechanism of injury (fall vs nonfall) and effect of TBI severity (mild vs moderate/severe) and TBI frequency (1 TBI vs >1 TBI). RESULTS: TBI patients were significantly more likely to be diagnosed with PD compared to NTT patients (1.7% vs 1.1%, p < 0.001, adjusted hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58). Risk of PD was similar for TBI sustained via falls versus nonfalls (interaction p = 0.6). Assessment by TBI severity (mild TBI: HR = 1.24, 95% CI = 1.04-1.48; moderate/severe TBI: HR = 1.50, 95% CI = 1.35-1.66) and TBI frequency (1 TBI: HR = 1.45, 95% CI = 1.30-1.60; >1 TBI: HR = 1.87, 95% CI = 1.58-2.21) revealed a dose response. INTERPRETATION: Among patients aged ≥55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation.

Cognitive resilience to apolipoprotein E ε4: contributing factors in black and white older adults.

IMPORTANCE: Apolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. OBJECTIVE: Using APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE ε4 carriers. DESIGN, SETTING, AND PARTICIPANTS: Participants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE ε4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination. MAIN OUTCOMES AND MEASURES: We stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE ε4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE ε4 carriers. RESULTS: Among white APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE ε4 carriers. Among black APOE ε4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience. CONCLUSIONS AND RELEVANCE: Although APOE ε4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE ε4 carriers.

Development and validation of risk index for cognitive decline using blood-derived markers.

OBJECTIVE: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. METHODS: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma ß-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. RESULTS: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included ß-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: -1.14, -0.51). CONCLUSIONS: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary.

Impact of electronic health record clinical decision support on the management of pediatric obesity.

Clinicians vary significantly in their adherence to clinical guidelines for overweight/obesity. This study assessed the impact of electronic health record-based clinical decision support in improving the diagnosis and management of pediatric obesity. The study team programmed a point-of-care alert linked to a checklist and standardized documentation templates to appear during health maintenance visits for overweight/obese children in an outpatient teaching clinic and compared outcomes through medical record reviews of 574 (287 control and 287 intervention) visits. The results demonstrated a statistically significant increase in the diagnosis of overweight/obesity, scheduling of follow-up appointments, frequency of ordering recommended laboratory investigations, and assessment and counseling for nutrition and physical activity. Although clinical guideline adherence increased significantly, it was far from universal. It is unknown if modest improvements in adherence to clinical guidelines translate to improvements in children's health. However, this intervention was relatively easy to implement and produced measurable improvements in health care delivery.

Athletic coaches as violence prevention advocates.

Adolescent relationship abuse (ARA) is a significant public health problem. Coaching Boys Into Men (CBIM) is an evidence-based ARA prevention program that trains coaches to deliver violence prevention messages to male athletes. Assessing acceptability and impact of CBIM on coaches may inform prevention efforts that involve these important adults in health promotion among youth. As part of a two-armed cluster-randomized controlled trial of CBIM in 16 high schools in Northern California, coaches completed baseline and postseason surveys (n = 176) to assess their attitudes and confidence delivering the program. Coaches in the intervention arm also participated in interviews (n = 36) that explored program acceptability, feasibility, and impact. Relative to controls, intervention coaches showed increases in confidence intervening when witnessing abusive behaviors among their athletes, greater bystander intervention, and greater frequency of violence-related discussions with athletes and other coaches. Coaches reported the program was easy to implement and valuable for their athletes. Findings illustrate the value of exploring attitudinal and behavioral changes among ARA prevention implementers, and suggest that coaches can gain confidence and enact behaviors to discourage ARA among male athletes. Coaches found the program to be feasible and valuable, which suggests potential for long-term uptake and sustainability.

Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity.

IMPORTANCE: Epidemiologic evidence regarding the importance of traumatic brain injury (TBI) as a risk factor for dementia is conflicting. Few previous studies have used patients with non-TBI trauma (NTT) as controls to investigate the influence of age and TBI severity. OBJECTIVE: To quantify the risk of dementia among adults with recent TBI compared with adults with NTT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed from January 1, 2005, through December 31, 2011 (follow-up, 5-7 years). All patients 55 years or older diagnosed as having TBI or NTT in 2005 and 2006 and who did not have baseline dementia or die during hospitalization (n = 164,661) were identified in a California statewide administrative health database of emergency department (ED) and inpatient visits. EXPOSURES: Mild vs moderate to severe TBI diagnosed by Centers for Disease Control and Prevention criteria using International Classification of Diseases, Ninth Revision (ICD-9)codes, and NTT, defined as fractures excluding fractures of the head and neck, diagnosed using ICD-9 codes. MAIN OUTCOMES AND MEASURES: Incident ED or inpatient diagnosis of dementia (using ICD-9 codes) 1 year or more after initial TBI or NTT. The association between TBI and risk of dementia was estimated using Cox proportional hazards models before and after adjusting for common dementia predictors and potential confounders. We also stratified by TBI severity and age category (55-64, 65-74, 75-84, and ≥85 years). RESULTS: A total of 51,799 patients with trauma (31.5%) had TBI. Of these, 4361 (8.4%) developed dementia compared with 6610 patients with NTT (5.9%) (P < .001). We found that TBI was associated with increased dementia risk (hazard ratio [HR], 1.46; 95% CI, 1.41-1.52; P < .001). Adjustment for covariates had little effect except adjustment for age category (fully adjusted model HR, 1.26; 95% CI, 1.21-1.32; P < .001). In stratified adjusted analyses, moderate to severe TBI was associated with increased risk of dementia across all ages (age 55-64: HR, 1.72; 95% CI, 1.40-2.10; P < .001; vs age 65-74: HR, 1.46; 95% CI, 1.30-1.64; P < .001), whereas mild TBI may be a more important risk factor with increasing age (age 55-64: HR, 1.11; 95% CI, 0.80-1.53; P = .55; vs age 65-74: HR, 1.25; 95% CI, 1.04-1.51; P = .02; age interaction P < .001). CONCLUSIONS AND RELEVANCE: Among patients evaluated in the ED or inpatient settings, those with moderate to severe TBI at 55 years or older or mild TBI at 65 years or older had an increased risk of developing dementia. Younger adults may be more resilient to the effects of recent mild TBI than older adults.

The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: a longitudinal study.

Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and function of neurons. Although persons with Alzheimer's disease have lower cortical levels of BDNF, evidence regarding the association between circulating BDNF and cognitive function is conflicting. We sought to determine the correlates of BDNF level and whether BDNF level was prospectively associated with cognitive decline in healthy older adults. We measured serum BDNF near baseline in 912 individuals. Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years. We evaluated the association between BDNF and cognitive decline with longitudinal models. We also assessed the association between BDNF level and demographics, comorbidities and health behaviors. We found an association between serum BDNF and several characteristics that are also associated with dementia (race and depression), suggesting that future studies should control for these potential confounders. We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults, although we did identify a potential trend toward a cross-sectional association. Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline.

Biological heterogeneity in ADNI amnestic mild cognitive impairment.

BACKGROUND: Previous work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications. METHODS: ADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion. RESULTS: Four clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD. CONCLUSIONS: Subjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.

Collaborative practice improvement for childhood obesity in rural clinics: the Healthy Eating Active Living Telehealth Community of Practice (HEALTH COP).

This study assessed the impact of participation in a virtual quality improvement (QI) learning network on adherence to clinical guidelines for childhood obesity prevention in rural clinics. A total of 7 primary care clinics in rural California included in the Healthy Eating Active Living TeleHealth Community of Practice and 288 children seen in these clinics for well-child care participated in this prospective observational pre-post study. Clinics participated in a virtual QI learning network over 9 months to implement best practices and to exchange strategies for improvement. Following the intervention, documentation of weight assessment and counseling increased significantly. Children who received care from clinicians who led the implementation of the intervention at their clinic showed significant improvements in nutrition and physical activity. Virtual QI learning networks in geographically dispersed clinics can significantly increase clinicians' adherence to guidelines for childhood obesity and improve access to recommended care for rural and underserved children.

Evaluation of a gender-based violence prevention program for student athletes in Mumbai, India.

Gender-based violence, which includes sexual and intimate partner violence against women, is prevalent worldwide, prompting calls for primary prevention programs which engage men and boys in changing social norms that condone violence against women. Bystander intervention efforts which encourage males to say something to stop peers from enacting disrespectful and abusive behaviors toward females are a promising strategy for promoting non-violent, gender-equitable attitudes and behaviors. An evaluation of "Parivartan"--a U.S. program called "Coaching Boys Into Men" adapted for urban India cricket teams--was conducted in Mumbai, India. Baseline and 12 month follow-up surveys were administered to 309 male cricket athletes aged 10 to 16 years in 46 urban middle schools in Mumbai, India (27 intervention, 19 control). Athletes whose coaches were trained in the program demonstrated greater improvements in gender-equitable attitudes compared to athletes whose coaches provided standard coaching only. Marginally significant improvements were seen in reduction of negative bystander behavior. Violence prevention programs which utilize coaches as positive messengers for respect and non-violence may be a useful addition to global prevention efforts to reduce violence against women.

Telemedicine and face-to-face care for pediatric obesity.

The University of California Davis Medical Center (Sacramento, CA) has pioneered the use of telemedicine in its approach to childhood obesity to cover more than 20 rural clinics in California. In our study, we compared the outcomes of the Telemedicine Weight Management Clinic (TM) with those of its face-to-face (FTF) Weight Management Clinic counterpart over the last 5 years, predicting the results to be equivalent or in favor of TM. All children seen in the TM from June 2006 to June 2011 were included (n=121), and encounter notes in medical records were reviewed. For comparison, an equivalent sample of FTF patients was selected from that time frame (n=122). Data that were also abstracted from the medical record included age at first visit, gender, race, referral site, and comorbid diagnoses. Forty-two percent of TM patients compared with 52% of FTF patients received a change in diagnosis. Thirty-nine percent of TM patients received a change in diagnostic evaluation compared with 67% of patients in FTF. When comparing patients who received more than one visit with either form of consultation, the TM group demonstrated substantially more improvement than the FTF group in improving nutrition (88% versus 65%), increasing activity (76% versus 49%), and decreasing screen time (33% versus 8%). Substantially more TM patients were successful with a combined outcome of any one of the weight parameters that included weight loss, weight maintenance, or slowing of weight gain (69% TM versus 44% FTF). Our study suggests that telemedicine can serve as a feasible strategy to increase access to medical care for childhood obesity in rural communities and promote changes in lifestyle with the goal of maintaining a healthy weight.

Improving knowledge, awareness, and use of flexible career policies through an accelerator intervention at the University of California, Davis, School of Medicine.

The challenges of balancing a career and family life disproportionately affect women in academic health sciences and medicine, contributing to their slower career advancement and/or their attrition from academia. In this article, the authors first describe their experiences at the University of California, Davis, School of Medicine developing and implementing an innovative accelerator intervention designed to promote faculty work-life balance by improving knowledge, awareness, and access to comprehensive flexible career policies. They then summarize the results of two faculty surveys--one conducted before the implementation of their intervention and the second conducted one year into their three-year intervention--designed to assess faculty's use and intention to use the flexible career policies, their awareness of available options, barriers to their use of the policies, and their career satisfaction. The authors found that the intervention significantly increased awareness of the policies and attendance at related educational activities, improved attitudes toward the policies, and decreased perceived barriers to use. These results, however, were most pronounced for female faculty and faculty under the age of 50. The authors next discuss areas for future research on faculty use of flexible career policies and offer recommendations for other institutions of higher education--not just those in academic medicine--interested in implementing a similar intervention. They conclude that having flexible career policies alone is not enough to stem the attrition of female faculty. Such policies must be fully integrated into an institution's culture such that faculty are both aware of them and willing to use them.

Targeted versus tailored multimedia patient engagement to enhance depression recognition and treatment in primary care: randomized controlled trial protocol for the AMEP2 study.

BACKGROUND: Depression in primary care is common, yet this costly and disabling condition remains underdiagnosed and undertreated. Persisting gaps in the primary care of depression are due in part to patients' reluctance to bring depressive symptoms to the attention of their primary care clinician and, when depression is diagnosed, to accept initial treatment for the condition. Both targeted and tailored communication strategies offer promise for fomenting discussion and reducing barriers to appropriate initial treatment of depression. METHODS/DESIGN: The Activating Messages to Enhance Primary Care Practice (AMEP2) Study is a stratified randomized controlled trial comparing two computerized multimedia patient interventions -- one targeted (to patient gender and income level) and one tailored (to level of depressive symptoms, visit agenda, treatment preferences, depression causal attributions, communication self-efficacy and stigma)-- and an attention control. AMEP2 consists of two linked sub-studies, one focusing on patients with significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥ 5), the other on patients with few or no depressive symptoms (PHQ-9 < 5). The first sub-study examined effectiveness of the interventions; key outcomes included delivery of components of initial depression care (antidepressant prescription or mental health referral). The second sub-study tracked potential hazards (clinical distraction and overtreatment). A telephone interview screening procedure assessed patients for eligibility and oversampled patients with significant depressive symptoms. Sampled, consenting patients used computers to answer survey questions, be randomized, and view assigned interventions just before scheduled primary care office visits. Patient surveys were also collected immediately post-visit and 12 weeks later. Physicians completed brief reporting forms after each patient's index visit. Additional data were obtained from medical record abstraction and visit audio recordings. Of 6,191 patients assessed, 867 were randomized and included in analysis, with 559 in the first sub-study and 308 in the second. DISCUSSION: Based on formative research, we developed two novel multimedia programs for encouraging patients to discuss depressive symptoms with their primary care clinicians. Our computer-based enrollment and randomization procedures ensured that randomization was fully concealed and data missingness minimized. Analyses will focus on the interventions' potential benefits among depressed persons, and the potential hazards among the non-depressed. TRIAL REGISTRATION: ClinicialTrials.gov Identifier: NCT01144104.

Subgroup of ADNI normal controls characterized by atrophy and cognitive decline associated with vascular damage.

Previous work examining Alzheimer's Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey's Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings.

Improving pediatric health care delivery by engaging residents in team-based quality improvement projects.

The goal was to implement and evaluate an experimental and longitudinal team-based curriculum in quality improvement (QI) for pediatric residents that would increase their ability to apply QI methodology while improving clinical processes and outcomes. The curriculum evolved over 3 years based on resident feedback. Working in teams, residents and faculty apply QI principles to systematically design and implement QI projects. Residents increased their level of comfort with key QI concepts. They showed an increase in QI skills by meaningful integration of the following QI concepts into their projects: establishing the magnitude of the problem, developing focused aims for improvement, identifying areas to change, using QI tools, collecting data, and assessing if changes were successful. The 10 resident-led projects conducted over the past 3 years also resulted in improvements in measures of multiple clinical processes and outcomes. This curriculum was effective and feasible within the constraints of residency work hours.