Type 2 diabetes is one of the fastest growing chronic diseases internationally. The health complications associated with type 2 diabetes can be prevented, delayed, or improved via early diagnosis and effective management. This research aims to examine the impact of a primarily web-based educational intervention on the diabetes care provided by general practitioners (GPs) in rural areas, and subsequent patient outcomes. A population-level approach to outcome assessment is used, via whole-town de-identified pathology records.
The study uses a cluster randomised controlled trial with rural communities as the unit of analysis. Towns from four Australian states were selected and matched on factors including rurality, population size, proportion of the population who were Indigenous Australians, and socio-economic status. Eleven pairs of towns from two states were suitable for the trial, and one town from each pair was randomised to the experimental group. GPs in the towns allocated to the experimental group are offered an intervention package comprising education on best practice diabetes care via an on-line active learning module, a moderated discussion forum, access to targeted and specialist advice through an on-line request form, and town-based performance feedback on diabetes monitoring and outcomes. The package is offered via repeated direct mail.
The benefits of the outcomes of the trial are described along with the challenges and limitations associated with the methodology.
Australian New Zealand Clinical Trials Registry: ACTRN12611000553976
Type 2 diabetes mellitus; Cluster randomised controlled trial; Internet; Medical education; General practitioner
Meta-analysis based techniques are emerging as powerful, robust tools for developing models of connectivity in functional neuroimaging. Here, we apply meta-analytic connectivity modeling to the human caudate to 1) develop a model of functional connectivity, 2) determine if meta-analytic methods are sufficiently sensitive to detect behavioral domain specificity within region-specific functional connectivity networks, and 3) compare meta-analytic driven segmentation to structural connectivity parcellation using diffusion tensor imaging. Results demonstrate strong coherence between meta-analytic and data-driven methods. Specifically, we found that behavioral filtering resulted in cognition and emotion related structures and networks primarily localized to the head of the caudate nucleus, while perceptual and action specific regions localized to the body of the caudate, consistent with early models of nonhuman primate histological studies and postmortem studies in humans. Diffusion tensor imaging (DTI) revealed support for meta-analytic connectivity modeling's (MACM) utility in identifying both direct and indirect connectivity. Our results provide further validation of meta-analytic connectivity modeling, while also highlighting an additional potential, namely the extraction of behavioral domain specific functional connectivity.
meta-analytic connectivity modeling; functional connectivity; MACM; DTI; caudate
Most cardiovascular disease (CVD) occurs after age 65. The additive benefits of aggressive risk factor management with advancing age are not well established.
Evaluate the relationship between control of 4 modifiable risk factors [smoking, non-high density lipoprotein cholesterol (non-HDL-C), blood pressure, and aspirin use] and CVD risk in a primary prevention population of older men.
Physicians’ Health Study participants who in 1997 were ≥65 years and had a blood sample. Cox proportional hazard models were adjusted for age and competing causes of death.
U.S. male physicians from epidemiologic follow-up of a randomized trial of aspirin and beta-carotene.
4182 men aged ≥65 years free of CVD and diabetes.
Main outcome measure
First of any CVD event, defined as cardiovascular death, non-fatal myocardial infarction, angina, coronary revascularization, non-fatal stroke, transient ischemic attack, carotid artery surgery, and other peripheral vascular disease surgery.
Mean follow-up was 9.3 years, mean age was 73 years, and 96% were nonsmokers. Compared to when 4 of 4 risk factors were controlled (6.0% of participants), control of 0 of 4 risk factors almost quadrupled CVD risk (0.4% of participants; event rate 41.2%; HR 3.83, 95% CI 1.72–8.55); control of 1 of 4 risk factors more than double the risk (14.2% of participants; HR 2.53, 95% CI 1.80–3.57); control of 2 of 4 risk factors almost doubled risk (43.8% of participants; HR 1.94, 95% CI 1.41–2.69), and those with control of 3 of 4 risk factors also were at increased risk (35.6% of participants; HR 1.80, 95% CI 1.30–2.50). Control of each additional risk factor was associated with greater cardiovascular protection (p for trend p=0.002). Depending on the number of risk factors controlled, the number-needed to control to prevent one CVD event ranged from 5 to 22.
Control of 4 treatable risk factors (nonsmoking, control of non-HDL-C and blood pressure, and aspirin use) were associated with substantial protection against incident cardiovascular events in older men even after adjustment for competing causes of mortality.
This study was designed to evaluate the clinical and prognostic aspects of long QT syndrome-related cardiac events that occur in the first year of life (infancy).
The clinical implications for patients with long QT syndrome who experience cardiac events in infancy have not been studied previously.
The study population of 3,323 patients with QTc ≥ 450 ms enrolled in the International LQTS Registry involved 20 patients with sudden cardiac death (SCD), 16 patients with aborted cardiac arrest (ACA), 34 patients with syncope, and 3,253 patients who were asymptomatic during the first year of life.
The risk factors for a cardiac event among 212 patients who had an ECG recorded in the first year of life included QTc≥500ms, heart rate ≤100bpm, and female sex. ACA before age 1 year was associated with a hazard ratio of 23.4 (p<0.01) for ACA or SCD during age 1-10 years. During the 10-year follow-up after infancy, beta-blocker therapy was associated with a significant reduction in ACA/SCD only in those with a syncopal episode within 2 years before ACA/SCD, but not for those who survived ACA in infancy.
Patients with LQTS who experience ACA during the first year of life are at very high-risk for subsequent ACA or death during their next 10 years of life, and beta-blockers may not be effective in preventing fatal or near fatal cardiac events in this small but high-risk subset.
Long QT Syndrome; Genetics; Infants; Risk Stratification
Background. Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman's overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. Materials and Methods. We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations. Results. Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking. Conclusions. HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.
Genome-wide association studies have identified several genomic regions that are associated with stroke risk, but these provide an explanation for only a small fraction of familial stroke aggregation. Genotype by environment interactions may contribute further to such an explanation. The Women's Health Initiative (WHI) clinical trial found increased stroke risk with postmenopausal hormone therapy (HT) and provides an efficient setting for evaluating genotype-HT interaction on stroke risk.
We examined HT by genotype interactions for 392 SNPs selected from candidate gene studies, and 2,371 SNPs associated with changes in blood protein concentrations after hormone therapy, in analyses that included 2,045 postmenopausal women who developed stroke during WHI clinical trial and observational study follow-up and one-to-one matched controls. A two-stage procedure was implemented where SNPs passing the first stage screening based on marginal association with stroke risk were tested in the second stage for interaction with HT using case-only analysis.
The two-stage procedure identified two SNPs, rs2154299 and rs12194855, in the coagulation factor XIII subunit A (F13A1) region and two SNPs, rs630431 and rs560892, in the proprotein convertase subtilisin kexin 9 (PCSK9) region, with an estimated false discovery rate <0.05 based on interaction tests. Further analyses showed significant stroke risk interaction between these F13A1 SNPs and estrogen plus progestin (E+P) treatment for ischemic stroke and for ischemic and hemorrhagic stroke combined, and suggested interactions between PCSK9 SNPs with either E+P or estrogen-alone treatment.
Genotype by environment interaction information may help to define genomic regions relevant to stroke risk. Two-stage analysis among postmenopausal women generates novel hypotheses concerning the F13A1 and PCSK9 genomic regions and the effects of hormonal exposures on postmenopausal stroke risk for subsequent independent validation.
Whether fish or the fatty acids they contain are independently associated with risk for incident heart failure (HF) among postmenopausal women is unclear.
Methods and Results
The baseline Women’s Health Initiative Observational Study (WHI-OS) cohort consisted of 93,676 women aged 50–79 of diverse ethnicity and background of which 84,493 were eligible for analyses. Intakes of baked/broiled fish, fried fish and omega-3 fatty acid (eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), α-linolenic acid (ALA)), and trans fatty acid (TFA) were determined from the WHI food frequency questionnaire. Baked/broiled fish consumption was divided into 5 frequency categories: <1/mo (referent), 1–3/mo, 1–2/wk, 3–4/wk, ≥5/wk. Fried fish intake was grouped into 3 frequency categories: <1/mo (referent), 2) 1–3/mo, and 3) ≥1/wk. Associations between fish or fatty acid intake and incident HF were determined using Cox models adjusting for HF risk factors and dietary factors. Baked/broiled fish consumption (≥5 servings/wk at baseline) was associated with a hazard ratio (HR) of 0.70 (95% CI: 0.51, 0.95) for incident HF. In contrast, fried fish consumption (≥1 serving/wk at baseline) was associated with a HR of 1.48 (95% CI: 1.19, 1.84) for incident HF. No significant associations were found between EPA+DHA, ALA, or TFA intake and incident HF.
Increased baked/broiled fish intake may lower HF risk, while increased fried fish intake may increase HF risk in postmenopausal women.
heart failure; epidemiology; nutrition; women
Women with congenital long-QT syndrome (LQTS) experience increased risk for cardiac events after the onset of adolescence, that is more pronounced among carriers of the LQT2 genotype. We hypothesized that the hormonal changes associated with menopause may affect clinical risk in this population.
Methods and Results
We used a repeated events analysis to evaluate the risk for recurrent syncope during the menopause-transition and post-menopausal periods (5-years before and after the age at onset of menopause, respectively) among 282 LQT1 (n=151) and LQT2 (n=131) women enrolled in the LQTS Registry. Multivariate analysis showed that the risk for recurrent syncope (n=150) among LQT2 women was significantly increased during both menopause-transition (HR = 3.38 [p = 0.005]) and the post-menopausal period (HR = 8.10 [p < 0.001]) as compared with the reproductive period. The risk increase was evident among women who did or did not receive estrogen therapy. In contrast, among LQT1 women the onset of menopause was associated with a reduction in the risk for recurrent syncope (HR = 0.19 [p = 0.05]; p-value for genotype-by-menopause interaction = 0.02). Only 22 women (8%) experienced aborted cardiac arrest (ACA) or sudden cardiac death (SCD) during follow-up. The frequency of ACA/SCD showed a similar genotype-specific association with the onset of menopause.
The onset of menopause is associated with a significant increase in the risk of cardiac events (dominated by recurrent episodes of syncope) in LQT2 women, suggesting that careful follow-up and continued long-term therapy are warranted in this population.
long-QT syndrome; women; estrogen; testosterone
Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events.
We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene.
The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2–S3 and S4–S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations).
Multivariate analysis showed that during childhood (age group: 0–13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥500 ms) was associated with a higher risk among women than among men.
Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.
Cytoplasmic-loop mutations; Sex; Long QT syndrome; Sudden cardiac death
Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded IKs cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder.
Methods and Results
We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands’ LQTS Registry (n=93), and the Japanese LQTS Registry (n=82). The Cox proportional hazards survivorship model was used to evaluate the independent contribution of clinical and genetic factors to the first occurrence of time-dependent cardiac events from birth through age 40 years. The clinical characteristics, distribution of mutations, and overall outcome event rates were similar in patients enrolled from the 3 geographic regions. Biophysical function of the mutations was categorized according to dominant-negative (>50%) or haploinsufficiency (≤50%) reduction in cardiac repolarizing IKs potassium channel current. Patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06; P<0.001) and those with mutations having dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26; P<0.001) were at increased risk for cardiac events, and these genetic risks were independent of traditional clinical risk factors.
This genotype–phenotype study indicates that in type-1 LQTS, mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder.
electrocardiography; genetics; long-QT syndrome
This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals.
Current data regarding the outcome of patients with concealed LQTS are limited.
Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤440 ms [n = 469]), LQTS with prolonged QTc interval (>440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤440 ms [n = 1,525]).
The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002).
Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup.
corrected QT interval; long-QT syndrome; sudden cardiac death
The Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5×10−11), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2×10−36). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.
To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes.
RESEARCH DESIGN AND METHODS
A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50–<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors.
Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial.
Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.
We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS).
Data regarding risk assessment in LQTS after the occurrence of first syncope are limited.
The Prentice-Williams-Peterson conditional gap time model was utilized to identify risk factors for recurrent syncope from birth through age 20 years among 1648 patients from the International LQTS Registry.
Multivariate analysis demonstrated that QTc duration (≥500 msec) was a significant predictor of a first syncope (HR=2.16), whereas QTc effect was attenuated when the endpoints of second-, third-, and fourth- syncope were evaluated (HR = 1.29, 0.99, 0.90, respectively; p<0.001 for the null hypothesis that all four HRs are identical). A genotype-specific sub-analysis showed that during childhood (0–12 years) LQT1 males had the highest rate of first syncope (p=0.001), but exhibited similar rates of subsequent events as other genotype-gender subsets (p=0.63). In contrast, in the age-range of 13–20 years, LQT2 females experienced the highest rate of both first and subsequent events (p<0.001 and p=0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6–12-fold (p<0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.
Children and adolescents who present following an episode of syncope should be considered to be at a high a risk for the development of subsequent syncopal episodes and fatal/near-fatal events regardless of QTc duration.
long qt syndrome; corrected QT interval; reccurrent events; syncope; sudden cardiac death
Cardiac events in long-QT syndrome type-2 (LQT2) patients are predominately associated with sudden arousal. However, exercise-induced events also occur in this population.
We hypothesized that risk factors show a trigger-specific association with cardiac events in LQT2 patients.
The study population comprised 634 genetically-confirmed LQT2 patients from the US portion of the International LQTS Registry. Multivariate Cox proportional hazards regression analysis was used to determine the independent contribution of clinical and genetic risk factors to the first occurrence of trigger-specific cardiac events, categorized as arousal, exercise-induced, and non-arousal/non-exercise, from birth through age 40 years.
Study patients experienced 204 cardiac events during follow-up, of which 44% were associated with arousal-triggers, 13% with exercise activity, and 43% with non-exercise/non-arousal triggers. Risk factors for arousal triggered cardiac events included gender (female:male >13 years: HR=9.10 [p<0.001]), and the presence of pore-loop mutations (HR=2.19 [p=0.009]). In contrast, non pore-loop transmembrane mutations were the predominant risk factor for exercise-triggered events (HR=6.84 [p<0.001]), whereas gender was not a significant risk factor for this end point. Non-exercise/non-arousal events were associated with heterogeneous causes. Risk factors for this end point included gender, mutation-location and type, and a prolonged QTc (≥500 msec) Beta-blocker therapy was associated with a pronounced reduction in the risk of exercise-triggered events (HR=0.29 [p<0.01]), but had a non-significant effect on the risk of arousal- and non-exercise/non-arousal events.
Our findings suggest that management of patients with the LQT2 genotype should employ a trigger-specific approach to risk-assessment and medical therapy.
long-QT syndrome; ion channel mutations; sudden cardiac death; risk factors; beta-blockers
Statins are the evidence-based drugs of choice for the prevention of cardiovascular disease (CVD).
Statin utilization has increased in those ≥65 years, but patterns of utilization in subgroups of elderly are unknown.
Weighted data from the 2001 through 2006 National Health and Nutrition Examination Surveys were combined for this analysis.
Statin use increased in all sex, age, and risk categories between the 2001-2002 and 2005-2006 surveys, when the highest use was by men aged 65-74 years with CVD (80%), followed by women with CVD aged 65-79 (64-69%), women and men with diabetes aged 65-69 (56 and 94%, respectively); statins were used by <42% of individuals without CVD or diabetes. In adjusted logistic regression models, those with diabetes [odds ratio (OR) 2.1, 95% CI 1.8-2.6], CVD but no diabetes (OR 3.0, 95% CI 2.5-3.6), and CVD and diabetes (OR 5.2, 95% CI 3.9-7.1) were more likely to use statins than those without CVD or diabetes, p=<0.001. A significant interaction between age and gender was found, where 75-79 year old women were more likely to report statin use than men aged 65-69 (OR = 2.07, 95% CI = 1.29, 3.35). In general, those aged 65-69 were more likely to use a statin than those ≥70 (OR 0.57, 95% CI 0.39-1.08, p=0.08). Non-white persons aged ≥70 reported less statin use than whites aged 65-69 (OR=0.17, 95% CI 0.10-0.30). Mexican Americans were less likely to report statin use than whites.
Although statin use has increased substantially over time, statins remain underutilized in both the primary and secondary prevention of CVD in the elderly, with some evidence of disparities by sex, advancing age, and race/ethnicity.
Lipids; Statins; Elderly; Prevention; Population; Cardiovascular disease
Neuroimaging researchers have developed rigorous community data and metadata standards that encourage meta-analysis as a method for establishing robust and meaningful convergence of knowledge of human brain structure and function. Capitalizing on these standards, the BrainMap project offers databases, software applications, and other associated tools for supporting and promoting quantitative coordinate-based meta-analysis of the structural and functional neuroimaging literature.
In this report, we describe recent technical updates to the project and provide an educational description for performing meta-analyses in the BrainMap environment.
The BrainMap project will continue to evolve in response to the meta-analytic needs of biomedical researchers in the structural and functional neuroimaging communities. Future work on the BrainMap project regarding software and hardware advances are also discussed.
functional neuroimaging; structural neuroimaging; meta-analysis; BrainMap; neuroinformatics; activation likelihood estimation; ALE
To determine if body weight (BMI) is independently associated with cognitive function in postmenopausal women and the relationship between body fat distribution as estimated by waist-hip-ratio (WHR) and cognitive function.
Cross-sectional data analysis
Baseline data from the Women's Health Initiative (WHI) hormone trials.
8745 postmenopausal women aged 65–79 years, free of clinical evidence of dementia and completed baseline evaluation in the Women's Health Initiative (WHI) hormone trials.
Participants completed a Modified Mini-Mental State Examination (3MSE), health and lifestyle questionnaires, and standardized measurements of height, weight, body circumferences and blood pressure. Statistical analysis of associations between 3MSE scores, BMI and WHR after controlling for known confounders.
With the exception of smoking and exercise, vascular disease risk factors, including hypertension, waist measurement, heart disease and diabetes, were significantly associated with 3MSE score and were included as co-variables in subsequent analyses. BMI was inversely related to 3MSE scores, for every 1 unit increase in BMI, 3MSE decrease 0.988 (p=.0001) after adjusting for age, education and vascular disease risk factors. BMI had the most pronounced association with poorer cognitive functioning scores among women with smaller waist measurements. Among women with the highest WHR, cognitive scores increased with BMI.
Increasing BMI is associated with poorer cognitive function in women with smaller WHR. Higher WHR, estimating central fat mass, is associated with higher cognitive function in this cross-sectional study. Further research is needed to clarify the mechanism for this association.
obesity; cognition; dementia; waist-hip ratio; women
Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared coronary artery calcium scores among women randomized to calcium/vitamin D supplementation versus placebo following trial completion.
In an ancillary substudy of women randomized to calcium carbonate (1000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) versus placebo, nested within the Women’s Health Initiative trial of estrogen among women with hysterectomy, we measured CAC with cardiac computed tomography in 754 women aged 50–59 years at randomization. Imaging for CAC was performed at 28 of 40 centers following a mean of 7 years of treatment and scans were read centrally. Coronary artery calcium scores were measured by a central reading center with masking to randomization assignments.
Post-trial CAC measurements were similar in women randomized to calcium/vitamin D supplementation (calcium/D) and those receiving placebo. The mean CAC score was 91.6 for calcium/D and 100.5 for placebo (rank test p-value=0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, ≥10, and ≥100) for calcium/D vs placebo were 0.92 (95% confidence interval, 0.64–1.34), 1.29 (0.88–1.87), and 0.90 (0.56–1.44), respectively. Corresponding odds ratios among women with >50% adherence to study pills and for higher levels of CAC (>300), were similar.
Treatment with moderate doses of calcium plus vitamin D3 did not appear to alter coronary artery calcified plaque burden among postmenopausal women.
calcium; vitamin D; supplementation; coronary artery calcification; coronary heart disease; women’s health
Spatial normalization of neuroimaging data is a standard step when assessing group effects. As a result of divergent analysis procedures due to different normalization algorithms or templates, not all published coordinates refer to the same neuroanatomical region. Specifically, the literature is populated with results in the form of MNI or Talairach coordinates, and their disparity can impede the comparison of results across different studies. This becomes particularly problematic in coordinate-based meta-analyses, wherein coordinate disparity should be corrected to reduce error and facilitate literature reviews. In this study, a quantitative comparison was performed on two corrections, the Brett transform (i.e., “mni2tal”), and the Lancaster transform (i.e., “icbm2tal”). Functional magnetic resonance imaging (fMRI) data acquired during a standard paired associates task indicated that the disparity between MNI and Talairach coordinates was better reduced via the Lancaster transform, as compared to the Brett transform. In addition, an activation likelihood estimation (ALE) meta-analysis of the paired associates literature revealed that a higher degree of concordance was obtained when using the Lancaster transform in the form of fewer, smaller, and more intense clusters. Based on these results, we recommend that the Lancaster transform be adopted as the community standard for reducing disparity between results reported as MNI or Talairach coordinates, and suggest that future spatial normalization strategies be designed to minimize this variability in the literature.
Talairach; MNI; coordinate disparity; spatial normalization; icbm2tal; mni2tal; Lancaster transform; Brett transform
Moderate alcohol consumption is associated with a reduced risk of total mortality among Caucasian women. Whether moderate alcohol consumption is associated with a reduced risk of total mortality among African American or hypertensive women is unclear.
We conducted a prospective study among 10,576 black and 105,610 white post-menopausal women from the Women’s Health Initiative, without a history of cancer or cardiovascular disease, who completed the baseline examinations in 1994–1998.
During the mean 8 years of follow-up, 5608 women died. Moderate drinking (1–<7 drinks/week) was associated with a lower risk of total mortality among Caucasians (hazard ratio (HR) =0.81, 95% CI=0.72–0.91) and hypertensives (HR=0.76, 95% CI=0.65–0.87) as compared with lifetime abstention from alcohol. Among African American moderate drinkers the risk of total mortality was HR=0.94, 95% CI=0.67–1.3. Current drinking (<1 drink/month or greater) was associated with a lower risk of mortality among Caucasians, including hypertensives and non-hypertensives, and hypertensive African Americans (HR=0.74, 95% CI=0.54–0.99) but not among non-hypertensive African Americans (HR=1.31, 95% CI=0.79–2.16). The stratified comparisons among African Americans were affected by the low prevalence of moderate drinking (14.6%) and the low mortality rate (37.5/10,000) among the non-hypertensive lifetime abstainers.
Moderate drinking is associated with a lower risk of total mortality among Caucasian women. Current drinking is associated with a lower risk of total mortality among Caucasians, regardless of hypertensive status, and hypertensive but not non-hypertensive African American women. The latter observation was affected by the low mortality rate among the African American non-hypertensive lifetime abstainers.
alcohol; hypertension; mortality; women; race/ethnicity
The 2007 update to the American Heart Association (AHA) Guidelines for Cardiovascular Disease Prevention in Women recommend a simplified approach to risk stratification. We assigned Women's Health Initiative (WHI) participants to risk categories as described in the guideline, and evaluated clinical event rates within and between strata.
Methods and Results
The WHI enrolled 161,808 women aged 50-79 years, and followed them prospectively for 7.8 years (mean). Applying the 2007 AHA guideline categories, 11% of women were high risk, 72% at-risk and 4% optimal risk; 13% of women did not fall into any category, that is, lacked risk factors but did not adhere to a healthy lifestyle (moderate intensity exercise for 30 minute most days and <7% of calories from saturated fat). Among high risk, at-risk and optimal risk women, rates of myocardial infarction (MI)/coronary death were 12.5, 3.1 and 1.1% /10-years (p for trend <0.0001); the event rate was 1.3% among women who could not be categorized. We observed a graded relationship between risk category and cardiovascular event rates for white, black, Hispanic and Asian women, although event rates differed among ethnic groups (p for interaction =0.002). The AHA guideline predicted coronary events with accuracy similar to current Framingham risk categories (Area under receiver operating characteristic curve [AUC] for Framingham risk 0.665, for AHA risk 0.664; p=0.94), but less well than proposed Framingham 10-year risk categories of <5%, 5-20%, >20% (AUC for Framingham risk 0.724, for AHA risk 0.664; p<0.0001).
Risk stratification as proposed in the 2007 AHA guideline is simple, accessible to patients and providers, and identifies cardiovascular risk with accuracy similar to that of the current Framingham algorithm.
women; prevention; risk factors
To implement a simulation-based educational experience focused on medical emergencies in an ambulatory pharmacy setting.
Second-year student pharmacists were assigned randomly to groups and played the role of pharmacists in a community pharmacy setting in which a simulated patient experienced 1 of 5 emergency scenarios: medication-related allergic reaction, acute asthma attack, hypoglycemia, myocardial infarction, and stroke. The students were expected to use patient assessment techniques to determine which emergency the simulated patient was experiencing and the appropriate intervention. Following each simulation, a debriefing session was conducted.
Eighty-two student pharmacists completed the simulation activity. Ninety-three percent of student groups correctly identified the emergency. A post-activity survey instrument was administered, and 83% of responders indicated this activity was effective or very effective.
Simulation of emergencies seen in an ambulatory pharmacy setting allowed students to assert knowledge, practice communication skills, apply assessment techniques, and work as a team in a low-risk environment.
patient simulation; community pharmacy; emergency care; ambulatory care
Functional neuroimaging has evolved into an indispensable tool for non-invasively investigating brain function. A recent development of such methodology is the creation of connectivity models for brain regions and related networks, efforts that have been inhibited by notable limitations. We present a new method for ascertaining functional connectivity of specific brain structures using meta-analytic connectivity modeling (MACM), along with validation of our method using a non-human primate database. Drawing from decades of neuroimaging research and spanning multiple behavioral domains, the method overcomes many weaknesses of conventional connectivity analyses and provides a simple, automated alternative to developing accurate and robust models of anatomically-defined human functional connectivity. Applying MACM to the amygdala, a small structure of the brain with a complex network of connections, we found high coherence with anatomical studies in non-human primates as well as human-based theoretical models of emotive-cognitive integration, providing evidence for this novel method’s utility.
meta-analysis; BrainMap; fMRI; PET; CoCoMac