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Evaluation of Long-Term Cryostorage of Brain Tissue Sections for Quantitative Histochemistry

Mon, 05/15/2017 - 2:05pm

Storage of tissue sections for long periods allows multiple samples, acquired over months or years, to be processed together, in the same reagents, for quantitative histochemical studies. Protocols for freezer storage of free-floating frozen sections using sucrose with different additives have been reported and assert that storage has no effect on histochemistry, but no quantitative support has been provided. The present study analyzed the efficacy of long-term storage of brain tissue sections at -80C in buffered 15% glycerol. To determine whether histochemical reactivity is affected, we analyzed 11 datasets from 80 monkey brains that had sections stored for up to 10 years. For processing, sections from multiple cases were removed from storage, thawed, and batch-processed at the same time for different histochemical measures, including IHC for neuronal nuclear antigen, parvalbumin, orexin-A, doublecortin, bromodeoxyuridine, the pro-form of brain-derived neurotrophic factor, and damaged myelin basic protein as well as a histochemical assay for hyaluronic acid. Results were quantified using stereology, optical densitometry, fluorescence intensity, or percent area stained. Multiple regression analyses controlling for age and sex demonstrated the general stability of these antigens for up to a decade when stored in 15% glycerol at -80C.

Emergency Radiology Practice Patterns: Shifts, Schedules, and Job Satisfaction

Mon, 05/15/2017 - 2:05pm

PURPOSE: To assess the practice environment of emergency radiologists with a focus on schedule, job satisfaction, and self-perception of health, wellness, and diagnostic accuracy. METHODS: A survey drawing from prior radiology and health care shift-work literature was distributed via e-mail to national societies, teleradiology groups, and private practices. The survey remained open for 4 weeks in 2016, with one reminder. Data were analyzed using hypothesis testing and logistic regression modeling. RESULTS: Response rate was 29.6% (327/1106); 69.1% of respondents (n = 226) were greater than 40 years old, 73% (n = 240) were male, and 87% (n = 284) practiced full time. With regard to annual overnight shifts (NS): 36% (n = 118) did none, 24.9% (n = 81) did 182 or more, and 15.6% (n = 51) did 119. There was a significant association between average NS worked per year and both perceived negative health effects (P < .01) and negative impact on memory (P < .01). There was an inverse association between overall job enjoyment and number of annual NS (P < .05). The odds of agreeing to the statement "I enjoy my job" for radiologists who work no NS is 2.21 times greater than for radiologists who work at least 119 NS, when shift length is held constant. Radiologists with 11+ years of experience who work no NS or 1 to 100 NS annually have lower odds of feeling overwhelmed when compared with those working the same number of NS with <10 years' experience. CONCLUSION: There is significant variation in emergency radiology practice patterns. Annual NS burden is associated with lower job satisfaction and negative health self-perception.

Surpass Flow Diverter for Treatment of Posterior Circulation Aneurysms

Mon, 05/15/2017 - 2:05pm

BACKGROUND AND PURPOSE: Flow diverters for the treatment of posterior circulation aneurysms remain controversial. We aimed to identify factors contributing to outcome measures in patients treated with the Surpass flow diverter for aneurysms in this location.

MATERIALS AND METHODS: We conducted an observational study of 53 patients who underwent flow-diverter treatment for posterior circulation aneurysms at 15 centers. Key outcome measures were mortality, complete aneurysm occlusion, and modified Rankin Scale score at follow-up.

RESULTS: At follow-up (median, 11.3 months; interquartile range, 5.9-12.7 months), 9 patients had died, resulting in an all-cause mortality rate of 17.3% (95% CI, 7%-27.6%); 7 deaths (14%) were directly related to the procedure and none occurred in patients with a baseline mRS score of zero. After adjusting for covariates, a baseline mRS of 3-5 was more significantly (P = .003) associated with a higher hazard ratio for death than a baseline mRS of 0-2 (hazard ratio, 17.11; 95% CI, 2.69-109.02). After adjusting for follow-up duration, a 1-point increase in the baseline mRS was significantly (P < .001) associated with higher values of mRS at follow-up (odds ratio, 2.93; 95% CI, 1.79-4.79). Follow-up angiography in 44 patients (median, 11.3 months; interquartile range, 5.9-12.7 months) showed complete aneurysm occlusion in 29 (66%; 95% CI, 50.1%-79.5%).

CONCLUSIONS: Clinical results of flow-diverter treatment of posterior circulation aneurysms depend very much on patient selection. In this study, poorer outcomes were related to the treatment of aneurysms in patients with higher baseline mRS scores. Angiographic results showed a high occlusion rate for this subset of complex aneurysms.

Revisiting the indirect signs of a temporal bone fracture: air, air, everywhere

Mon, 05/15/2017 - 2:05pm

BACKGROUND AND PURPOSE: The standard head CT protocol makes detection of a temporal bone fracture difficult. The purposes of our study are to revisit the finding of air in various locations around the temporal bone as an indirect sign of fracture and determine if findings could predict fracture pattern.

MATERIALS AND METHODS: We searched the radiology reports for the keyword "temporal bone fracture." We recorded the presence of air in multiple locations around the temporal bone and pneumocephalus, opacification of the mastoid air cells or the middle ear cavity, and dominant fracture pattern. Statistical analyses were performed using statistical software.

RESULTS: A total of 135 patients (mean age 40 +/- 20.1 years, 101 male, 34 female, range 1-91) had 152 fractures. At least one indirect finding was present in 143 (94.1%) fractures. Air was present adjacent to the styloid process in 94 (61.8%), in the temporomandibular joint in 80 (52.6%), adjacent to the mastoid process in 57 (37.5%), and along the adjacent dural venous sinus in 33 (21.7%) fractures. Mastoid opacification was present in 139 (91.4%) fractures. Opacification of the middle ear cavity was present in 121 (79.6%) fractures. A complex fracture significantly and positively correlated with pneumocephalus.

CONCLUSION: In the setting of trauma, air around the temporal bone and opacification of the mastoid air cells or middle ear cavity should prompt consideration of a temporal bone fracture even if the fracture line is not visible. The presence of pneumocephalus predicts a higher chance of complex fracture pattern.

Education Mitigates the Relationship of Stress and Mental Disorders Among Rural Indian Women

Mon, 05/15/2017 - 10:43am

BACKGROUND: Common mental disorders (CMD) are a constellation of mental health conditions that include depression, anxiety, and other related nonpsychotic affective disorders. Qualitative explanatory models of mental health among reproductive-aged women in India reveal that distress is strongly associated with CMD. The relationship of perceived stress and CMD might be attenuated or exacerbated based on an individual's sociodemographic characteristics.

OBJECTIVES: To screen for Common Mental Disorders (CMD) among reproductive-aged women from rural western India and explore how the relationship between perceived stress and CMD screening status varies by sociodemographic characteristics.

METHODS: Cross-sectional survey of 700 women from rural Gujarat, India. CMD screening status was assessed using Self-Reported Questionnaire 20 (SRQ-20). Factors associated with CMD screening status were evaluated using multivariable logistic regression. Effect modification for the relationship of perceived stress and CMD screening status was assessed using interaction terms and interpreted in terms of predicted probabilities.

FINDINGS: The analytic cohort included 663 women, with roughly 1 in 4 screening positive for CMD (157, 23.7%). Poor income, low education, food insecurity, and recurrent thoughts after traumatic events were associated with increased risk of positive CMD screen. Perceived stress was closely associated with CMD screening status. Higher education attenuated the relationship between high levels of stress and CMD screening status (82.3%, 88.8%, 32.9%; P value for trend: 0.03). Increasing income and age attenuated the link between moderate stress and CMD.

CONCLUSIONS: Our findings suggest a high burden of possible CMD among reproductive-aged women from rural western India. Higher education might mitigate the association between elevated stress and CMD. Future efforts to improve mental health in rural India should focus on preventing CMD by enhancing rural women's self-efficacy and problem-solving capabilities to overcome challenging life events and stressors, thereby reducing the risk of CMD.

Are There Two Types of Suicidal Ideation Among Women in Rural India

Mon, 05/15/2017 - 10:43am

We present descriptive findings from a cross-sectional survey conducted in rural Gujarat, India, that expands the discussion on suicide among young women and poses the question: Are there two types of suicidal ideation among women in rural India?

Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic

Mon, 05/15/2017 - 10:43am

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013-2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.

Defining the 5 and 3 landscape of the Drosophila transcriptome with Exo-seq and RNaseH-seq

Mon, 05/15/2017 - 10:43am

Cells regulate biological responses in part through changes in transcription start sites (TSS) or cleavage and polyadenylation sites (PAS). To fully understand gene regulatory networks, it is therefore critical to accurately annotate cell type-specific TSS and PAS. Here we present a simple and straightforward approach for genome-wide annotation of 5- and 3-RNA ends. Our approach reliably discerns bona fide PAS from false PAS that arise due to internal poly(A) tracts, a common problem with current PAS annotation methods. We applied our methodology to study the impact of temperature on the Drosophila melanogaster head transcriptome. We found hundreds of previously unidentified TSS and PAS which revealed two interesting phenomena: first, genes with multiple PASs tend to harbor a motif near the most proximal PAS, which likely represents a new cleavage and polyadenylation signal. Second, motif analysis of promoters of genes affected by temperature suggested that boundary element association factor of 32 kDa (BEAF-32) and DREF mediates a transcriptional program at warm temperatures, a result we validated in a fly line where beaf-32 is downregulated. These results demonstrate the utility of a high-throughput platform for complete experimental and computational analysis of mRNA-ends to improve gene annotation.

Pain and Pharmacologic Pain Management in Long-Stay Nursing Home Residents

Mon, 05/15/2017 - 10:43am

Prior studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set (MDS) 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after these important initiatives of: 1) prevalence and correlates of persistent pain; and 2) prevalence and correlates of untreated or undertreated persistent pain. We identified 1,387,405 long-stay residents in United States NHs between 2011-2012 with 2 MDS assessments 90 days apart. Pain was categorized as persistent (pain on both assessments), intermittent (pain on either assessment), or none. Pharmacologic pain management was classified as untreated pain (no scheduled or as needed medications received) or potentially undertreated (no scheduled received). Modified Poisson models adjusting for resident clustering within NHs provided adjusted prevalence ratios estimates (APR) and 95% confidence intervals (CI).The prevalence of persistent and intermittent pain was 19.5% and 19.2% respectively but varied substantially by age, gender, race/ethnicity, cognitive impairment, and cancer. Of residents in persistent pain, 6.4% and 32.0% were untreated or undertreated. Racial/ethnic minorities (non-Hispanic blacks vs. whites, APR=1.19, 95% CI: 1.13-1.25) and severely cognitively impaired residents (severe vs. no/mild APR=1.51, 95% CI: 1.44-1.57) had an increased prevalence of untreated and undertreated pain. One in five NH residents has persistent pain. Although this estimate is greatly improved, many residents may be undertreated. The disturbing disparities in untreated and undertreated pain need to be addressed.

Statin use and risk of multiple myeloma: An analysis from the Cancer Research Network

Mon, 05/15/2017 - 10:43am

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged >/=40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N=2532). For each case, 5 controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (>/=6 cumulative months) and risk of multiple, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

Show Back: Developing and Testing of a Simulation-Based Assessment Method for Identifying Problems in Self-Management of Medications in Older Adults

Mon, 05/15/2017 - 10:43am

In this study, we developed and tested a comprehensive simulation that assesses older adult medication self-management proficiency.

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity

Mon, 05/15/2017 - 10:42am

BACKGROUND: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.

OBJECTIVE: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.

METHODS: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups.

RESULTS: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3.

LIMITATIONS: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response.

CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

Differential Expression of Hedgehog and Snail in Cutaneous Fibrosing Disorders: Implications for Targeted Inhibition

Wed, 05/10/2017 - 9:24am

OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition.

METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 beta (GSK3-beta), beta-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray.

RESULTS: Ihh, but not Shh, was detected in a significantly larger proportion of cells for all case types. Ptch, GSK3-beta, and beta-catenin showed a gradient of expression: highest in NSF and keloid; moderate in normal skin, scar, and Hscar; and lowest in scleroderma. Snail expression was binary: low in normal skin but high in all fibrosing conditions studied.

CONCLUSIONS: Differential overexpression of Hedgehog and Snail in cutaneous fibrosing disorders demonstrates a role for targeted inhibition. Ptch, GSK3-beta, and beta-catenin can help differentiate scleroderma from NSF in histologically subtle cases. Differences in expression between keloid and hypertrophic scar support the concept that they are pathophysiologically distinct disorders. Our findings implicate Snail as a target for the prevention of fibrogenesis or fibrosis progression and may offer a means to assess response to therapy.

Does adding clinical data to administrative data improve agreement among hospital quality measures

Wed, 05/10/2017 - 9:24am

BACKGROUND: Hospital performance measures based on patient mortality and readmission have indicated modest rates of agreement. We examined if combining clinical data on laboratory tests and vital signs with administrative data leads to improved agreement with each other, and with other measures of hospital performance in the nation's largest integrated health care system.

METHODS: We used patient-level administrative and clinical data, and hospital-level data on quality indicators, for 2007-2010 from the Veterans Health Administration (VA). For patients admitted for acute myocardial infarction (AMI), heart failure (HF) and pneumonia we examined changes in hospital performance on 30-d mortality and 30-d readmission rates as a result of adding clinical data to administrative data. We evaluated whether this enhancement yielded improved measures of hospital quality, based on concordance with other hospital quality indicators.

RESULTS: For 30-d mortality, data enhancement improved model performance, and significantly changed hospital performance profiles; for 30-d readmission, the impact was modest. Concordance between enhanced measures of both outcomes, and with other hospital quality measures - including Joint Commission process measures, VA Surgical Quality Improvement Program (VASQIP) mortality and morbidity, and case volume - remained poor.

CONCLUSIONS: Adding laboratory tests and vital signs to measure hospital performance on mortality and readmission did not improve the poor rates of agreement across hospital quality indicators in the VA.

INTERPRETATION: Efforts to improve risk adjustment models should continue; however, evidence of validation should precede their use as reliable measures of quality.

A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material

Wed, 05/10/2017 - 9:24am

OBJECTIVE: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake.

METHODS: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos.

RESULTS: To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not.

CONCLUSION: We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.

Decade-Long Trends (2001 to 2011) in the Use of Evidence-Based Medical Therapies at the Time of Hospital Discharge for Patients Surviving Acute Myocardial Infarction

Wed, 05/10/2017 - 9:23am

Optimization of medical therapy during discharge planning is vital for improving patient outcomes after hospitalization for acute myocardial infarction (AMI). However, limited information is available about recent trends in the prescribing of evidence-based medical therapies in these patients, especially from a population-based perspective. We describe decade-long trends in the discharge prescribing of aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta blockers, and statins in hospital survivors of AMI. The study population consisted of 5,253 patients who were discharged from all 11 hospitals in central Massachusetts after AMI in 6 biennial periods from 2001 to 2011. Combination medical therapy (CMT) was defined as the prescription of all 4 cardiac medications at hospital discharge. The average age of this patient population was 69.2 years and 57.7% were men. Significant increases were observed in the use of CMT, from 25.6% in 2001 to 48.7% in 2011, with increases noted for each of the individual cardiac medications examined. Subgroup analysis also showed improvement in discharge prescriptions for P2Y12 inhibitors in patients who underwent a percutaneous coronary intervention. Presence of a do-not-resuscitate order, before co-morbidities, hospitalization for non-ST-segment elevation myocardial infarction, admission to a nonteaching hospital, and failure to undergo cardiac catheterization or a percutaneous coronary intervention were associated with underuse of CMT. In conclusion, our study demonstrates encouraging trends in the prescribing of evidence-based medications at hospital discharge for AMI. However, certain patient subgroups continue to be at risk for underuse of CMT, suggesting the need for strategies to enhance compliance with current practice guidelines.

Rheumatoid arthritis triple therapy compared with etanercept: difference in infectious and gastrointestinal adverse events

Wed, 05/10/2017 - 9:23am

Objective.: The main aim of this study was to examine the differences between triple therapy (T: SSZ and HCQ added to MTX) and etanercept (E) added to MTX with regard to the infectious and gastrointestinal (GI) adverse events (AEs) reported in The Rheumatoid Arthritis Comparison of Active Therapies Trial.

Methods.: The patients were 353 RA MTX incomplete responders who were randomized to T (n = 178) or E (n = 175). Of these, 88 patients were switched to the alternative treatment from the initial treatment (E or T) at 24 weeks per protocol. Infectious and GI serious AEs (SAEs) and non-serious AEs (NAEs) were reported during 48 and 4 weeks after the intervention period. Generalized linear models were used to estimate the incidence rate ratios (IRRs) of AEs between the two therapies.

Results.: Patients on E therapy were more likely to have infectious NAEs (IRR = 1.56, 95% CI: 1.11, 2.19). There was a greater number of infectious SAEs that occurred when patients received E than T therapy [12 E (6.9%) vs 4 T (2.2%), P = 0.19]. Pneumonia was the most common infectious SAE for both treatments [6 E (3.4%) and 2 T (1.1%)]. Conversely, patients who were on E were less likely to have GI NAEs than those on T therapy (IRR = 0.62, 95% CI: 0.40, 0.94). The most common GI SAE reported was GI haemorrhage, which occurred among three patients on E (1.7%).

Conclusion.: This study provides evidence of different likelihoods of infectious and GI AEs associated with two common, equally effective treatments for RA patients who have had incomplete responses to MTX.

Use of Risk Models to Predict Death in the Next Year Among Individual Ambulatory Patients With Heart Failure

Wed, 05/10/2017 - 9:23am

Importance: The clinical practice guidelines for heart failure recommend the use of validated risk models to estimate prognosis. Understanding how well models identify individuals who will die in the next year informs decision making for advanced treatments and hospice.

Objective: To quantify how risk models calculated in routine practice estimate more than 50% 1-year mortality among ambulatory patients with heart failure who die in the subsequent year.

Design, Setting, and Participants: Ambulatory adults with heart failure from 3 integrated health systems were enrolled between 2005 and 2008. The probability of death was estimated using the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk calculator. Baseline covariates were collected from electronic health records. Missing covariates were imputed. Estimated mortality was compared with actual mortality at both population and individual levels.

Main Outcomes and Measures: One-year mortality.

Results: Among 10930 patients with heart failure, the median age was 77 years, and 48.0% of these patients were female. In the year after study enrollment, 1661 patients died (15.9% by life-table analysis). At the population level, 1-year predicted mortality among the cohort was 9.7% for the SHFM (C statistic of 0.66) and 17.5% for the MAGGIC risk calculator (C statistic of 0.69). At the individual level, the SHFM predicted a more than 50% probability of dying in the next year for 8 of the 1661 patients who died (sensitivity for 1-year death was 0.5%) and for 5 patients who lived at least a year (positive predictive value, 61.5%). The MAGGIC risk calculator predicted a more than 50% probability of dying in the next year for 52 of the 1661 patients who died (sensitivity, 3.1%) and for 63 patients who lived at least a year (positive predictive value, 45.2%). Conversely, the SHFM estimated that 8496 patients (77.8%) had a less than 15% probability of dying at 1 year, yet this lower-risk end of the score range captured nearly two-thirds of deaths (n = 997); similarly, the MAGGIC risk calculator estimated a probability of dying of less than 25% for the majority of patients who died at 1 year (n = 914).

Conclusions and Relevance: Although heart failure risk models perform reasonably well at the population level, they do not reliably predict which individual patients will die in the next year.

Einstein, measurement, and prediction

Wed, 05/10/2017 - 9:23am

Delgado-Gomez et al. (2016) have provided an interesting example of the comparison of computerized adaptive testing (CAT) based on unidimensional item response theory (IRT) and a machine learning approach based on decision trees (DT) in the prediction of people who have a history of suicide attempts. ... In the following we attempt to better articulate the differences between the two statistical approaches so that practitioners and consumers of these methods will have a better understanding of their utilities.

Longitudinal analysis of changes in weight and waist circumference in relation to incident vasomotor symptoms: the Study of Women's Health Across the Nation (SWAN)

Wed, 05/10/2017 - 9:23am

OBJECTIVE: Greater body mass index (BMI) and body fat are associated with vasomotor symptoms (VMS). Thus, weight loss may prevent VMS. We analyzed whether concurrent BMI or waist circumference and/or changes in weight or waist circumference predicted incident VMS and whether these relations differed by menopause stage or race/ethnicity.

METHODS: Data from 10 follow-up visits for 1,546 participants in the Study of Women's Health Across the Nation who reported no VMS at baseline were modeled for time to first symptomatic visit in relation to concurrent BMI and waist circumference and change in weight and waist circumference during early and late menopause using discrete survival analyses, adjusting for covariates.

RESULTS: Greater concurrent BMI and waist circumference were significantly related to greater any and frequent (>/=6 d in the last 2 wk) incident VMS in early menopause and lower VMS risk in late menopause. Percentage weight change since baseline and since the prior visit was unrelated to incident any VMS in either menopause stage. Percentage weight change since baseline had a significant shallow U-shaped association with incident frequent VMS in early menopause (P = 0.02), a shallow inverse U-shape in late menopause (P = 0.02), and a significant interaction with menopause stage (P = 0.004) but not with race/ethnicity. Recent weight change was unassociated with incident VMS in either menopause stage. Results were similar for waist change.

CONCLUSIONS: Concurrent BMI and waist circumference were positively related to incident VMS in early menopause and negatively related in late menopause. Maintaining healthy weight in early menopause may help prevent VMS.