Comment on Comparative validation of nomograms predicting clinically insignificant prostate cancer. [Urology. 2013]
Despite the high prevalence of substance use disorder (SUD) and its frequent comorbidity with mental illness, individuals with SUD are less likely to receive effective SUD treatment from mental health practitioners than SUD counselors. Limited competence and interest in treating this clinical population are likely influenced by a lack of formal training in SUD treatment. Using a factorial survey-vignette design that included three clinical vignettes and a supplementary survey instrument, we investigated whether clinical psychology doctoral students differ in their level of negative emotional reactions toward clients with SUD versus major depressive disorder (MDD); whether they differ in their attributions for SUD versus MDD; and how their negative emotional reactions and attributions impact their interest in pursuing SUD clinical work. Participants were 155 clinical psychology graduate-level doctoral students (72% female). Participants endorsed more negative emotional reactions toward clients with SUD than toward clients with MDD. They were also more likely to identify poor willpower as the cause for SUD than for MDD. More than a third reported interest in working with SUD populations. Highest levels of interest were associated with prior professional and personal experience with SUD, four to six years of clinical experience, and postmodern theoretical orientation.
BACKGROUND: Although the benefits of early tracheostomy in patients dependent on ventilators are well established, the reasons for variation in time from intubation to tracheostomy remain unclear. We identified clinical and demographic disparities in time to tracheostomy.
METHODS: We performed a level 3 retrospective prognostic study by querying the University HealthSystem Consortium (2007-2010) for adult patients receiving a tracheostomy after initial intubation. Time to tracheostomy was designated early ( < 7 days) or late ( > 10 days). Cohorts were stratified by time to tracheostomy and compared using univariate tests of association and multivariable adjusted models.
RESULTS: A total of 49,191 patients underwent tracheostomy after initial intubation: 42% early (n = 21,029) and 58% late (n = 28,162). On both univariate and multivariable analyses, women, blacks, Hispanics, and patients receiving Medicaid were less likely to receive an early tracheostomy. Patients in the early group also experienced lower rates of mortality (OR, 0.84; 95% CI, 0.79-0.88).
CONCLUSIONS: Early tracheostomy was associated with increased survival. Yet, there were still significant disparities in time to tracheostomy according to sex, race, and type of insurance. Application of evidence-based algorithms for tracheostomy may reduce unequal treatment and improve overall mortality rates. Additional research into this apparent bias in referral/rendering of tracheostomy is needed.
A strong motivation for undertaking psychiatric gene discovery studies is to provide novel insights into unknown biology. Although attention-deficit hyperactivity disorder (ADHD) is highly heritable, and large, rare copy number variants (CNVs) contribute to risk, little is known about its pathogenesis and it remains commonly misunderstood. We assembled and pooled five ADHD and control CNV data sets from the United Kingdom, Ireland, United States of America, Northern Europe and Canada. Our aim was to test for enrichment of neurodevelopmental gene sets, implicated by recent exome-sequencing studies of (a) schizophrenia and (b) autism as a means of testing the hypothesis that common pathogenic mechanisms underlie ADHD and these other neurodevelopmental disorders. We also undertook hypothesis-free testing of all biological pathways. We observed significant enrichment of individual genes previously found to harbour schizophrenia de novo non-synonymous single-nucleotide variants (SNVs; P=5.4 x 10-4) and targets of the Fragile X mental retardation protein (P=0.0018). No enrichment was observed for activity-regulated cytoskeleton-associated protein (P=0.23) or N-methyl-D-aspartate receptor (P=0.74) post-synaptic signalling gene sets previously implicated in schizophrenia. Enrichment of ADHD CNV hits for genes impacted by autism de novo SNVs (P=0.019 for non-synonymous SNV genes) did not survive Bonferroni correction. Hypothesis-free testing yielded several highly significantly enriched biological pathways, including ion channel pathways. Enrichment findings were robust to multiple testing corrections and to sensitivity analyses that excluded the most significant sample. The findings reveal that CNVs in ADHD converge on biologically meaningful gene clusters, including ones now established as conferring risk of other neurodevelopmental disorders.
BACKGROUND: Payers and policy makers rely on studies of trends in acute myocardial infarction (AMI) hospitalizations and spending that count only hospitalizations where the AMI is the principal discharge diagnosis. Hospitalizations with AMI coded as a secondary diagnosis are ignored. The effects of excluding these hospitalizations on estimates of trends are unknown.
METHODS: Observational study of all AMI hospitalizations in Fee-for-Service Medicare beneficiaries 65 years and older, from 2002 through 2011.
RESULTS: We studied 3,663,137 hospitalizations with any AMI discharge diagnosis over 288,873,509 beneficiary-years. Of these, 66% had AMI coded as principal (versus secondary). From 2002 to 2011, AMI hospitalization rates declined 24.5% (from 1,485 per 100,000 beneficiary-years in 2002 to 1,122 in 2011). Meanwhile, the proportion of these hospitalizations with a secondary AMI diagnosis increased from 28% to 40%; by 2011 these secondary AMI hospitalizations accounted for 43% of all expenditures for hospitalizations with AMI, or $2.8 billion. Major changes in comorbidities, principal diagnoses and mean costs for hospitalizations with a non-principal AMI diagnosis occurred in the 2006-2008 timeframe.
CONCLUSIONS: Current estimates of the burden of AMI ignore an increasingly large proportion of overall AMI hospitalizations and spending. Changes in the characteristics of hospitalizations that coincided with major payment and policy changes suggest that non-clinical factors affect AMI coding. Failing to consider all AMIs could inflate estimates of population health improvements, overestimate the value of AMI prevention and treatment and underestimate current and future AMI burden and expenditures.
Paternal diet can impact metabolic phenotypes in offspring, but mechanisms underlying such intergenerational information transfer remain obscure. Here, we interrogate cytosine methylation patterns in sperm obtained from mice consuming one of three diets, generating whole genome methylation maps for four pools of sperm samples and for 12 individual sperm samples, as well as 61 genome-scale methylation maps. We find that "epivariation," either stochastic or due to unknown demographic or environmental factors, was a far stronger contributor to the sperm methylome than was the diet consumed. Variation in cytosine methylation was particularly dramatic over tandem repeat families, including ribosomal DNA (rDNA) repeats, but rDNA methylation was strongly correlated with genetic variation in rDNA copy number and was not influenced by paternal diet. These results identify loci of genetic and epigenetic lability in the mammalian genome but argue against a direct role for sperm cytosine methylation in dietary reprogramming of offspring metabolism.
Magnitude of and Prognostic Factors Associated With 1-Year Mortality After Hospital Discharge for Acute Decompensated Heart Failure Based on Ejection Fraction Findings
BACKGROUND: Limited data exist about the magnitude of and the factors associated with prognosis within 1 year for patients discharged from the hospital after acute decompensated heart failure. Data are particularly limited from the more generalizable perspective of a population-based investigation and should be further stratified according to currently recommended ejection fraction (EF) findings.
METHODS AND RESULTS: The hospital medical records of residents of the Worcester, Massachusetts, metropolitan area who were discharged after acute decompensated heart failure from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, 2004, and 2006 were reviewed. The average age of the 4025 study patients was 75 years, 93% were white, and 44% were men. Of these, 35% (n=1414) had reduced EF ( < /=40%), 13% (n=521) had borderline preserved EF (41-49%), and 52% (n=2090) had preserved EF ( > /=50%); at 1 year after discharge, death rates were 34%, 30%, and 29%, respectively (P=0.03). Older age, a history of chronic obstructive pulmonary disease, systolic blood pressure findings < 150 mm Hg on admission, and hyponatremia were important predictors of 1-year mortality for all study patients, whereas several comorbidities and physiological factors were differentially associated with 1-year death rates in patients with reduced, borderline preserved, and preserved EF.
CONCLUSIONS: This population-based study highlights the need for further contemporary research into the characteristics, treatment practices, natural history, and long-term outcomes of patients with acute decompensated heart failure and varying EF findings and reinforces ongoing discussions about whether different treatment guidelines may be needed for these patients to design more personalized treatment plans.
BACKGROUND: Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening.
OBJECTIVES: To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs).
METHODS: We analyzed two hundred and nineteen 2-minute pulse recordings from 121 participants with AF (n = 98), PACs (n = 15), or PVCs (n = 15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from preexisting AF. The PULSE-SMART app conducted pulse analysis using 3 methods (Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot). We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12-lead EKG or 3-lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n = 65) of app users.
RESULTS: The smartphone-based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real-time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was "useful" and "not complex" to use.
CONCLUSION: A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs.
Several recent studies link parental environments to phenotypes in subsequent generations. In this work, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA (sRNA) levels in mature sperm, with decreased let-7 levels and increased amounts of 5' fragments of glycine transfer RNAs (tRNAs). In testicular sperm, tRNA fragments are scarce but increase in abundance as sperm mature in the epididymis. Epididymosomes (vesicles that fuse with sperm during epididymal transit) carry RNA payloads matching those of mature sperm and can deliver RNAs to immature sperm in vitro. Functionally, tRNA-glycine-GCC fragments repress genes associated with the endogenous retroelement MERVL, in both embryonic stem cells and embryos. Our results shed light on sRNA biogenesis and its dietary regulation during posttesticular sperm maturation, and they also link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.
Reliability of Predicting Early Hospital Readmission After Discharge for an Acute Coronary Syndrome Using Claims-Based Data
Early rehospitalization after discharge for an acute coronary syndrome, including acute myocardial infarction (AMI), is generally considered undesirable. The Centers for Medicare and Medicaid Services (CMS) base hospital financial incentives on risk-adjusted readmission rates after AMI, using claims data in its adjustment models. Little is known about the contribution to readmission risk of factors not captured by claims. For 804 consecutive patients > 65 years discharged in 2011 to 2013 from 6 hospitals in Massachusetts and Georgia after an acute coronary syndrome, we compared a CMS-like readmission prediction model with an enhanced model incorporating additional clinical, psychosocial, and sociodemographic characteristics, after principal components analysis. Mean age was 73 years, 38% were women, 25% college educated, and 32% had a previous AMI; all-cause rehospitalization occurred within 30 days for 13%. In the enhanced model, previous coronary intervention (odds ratio [OR] = 2.05, 95% confidence interval [CI] 1.34 to 3.16; chronic kidney disease OR 1.89, 95% CI 1.15 to 3.10; low health literacy OR 1.75, 95% CI 1.14 to 2.69), lower serum sodium levels, and current nonsmoker status were positively associated with readmission. The discriminative ability of the enhanced versus the claims-based model was higher without evidence of overfitting. For example, for patients in the highest deciles of readmission likelihood, observed readmissions occurred in 24% for the claims-based model and 33% for the enhanced model. In conclusion, readmission may be influenced by measurable factors not in CMS' claims-based models and not controllable by hospitals. Incorporating additional factors into risk-adjusted readmission models may improve their accuracy and validity for use as indicators of hospital quality.
INTRODUCTION: Susceptibility to cigarette smoking, defined as the lack of a firm decision against smoking, is a strong predictor of regular smoking and addiction. Several modifiable risk factors have been identified among never cigarette smokers, and one potential factor of interest is waterpipe use. The purpose of this study is to determine the association of waterpipe use with susceptibility to cigarette smoking among never-smoking youth.
METHODS: In a pooled analysis of 17 Arab nations with nationally representative Global Youth Tobacco Surveys conducted during 2002-2011, tobacco-related information was obtained from 30,711 never-smoking adolescents representing 4,962,872 youth. Study outcome was susceptibility to cigarette smoking, and primary exposure was waterpipe use. Data were analyzed in 2014 using weighted logistic regression models, including stratified models by gender, to determine the odds of susceptibility to cigarette smoking with waterpipe use, adjusting for confounders.
RESULTS: Overall, 20% of never-smoking youth were susceptible to cigarette smoking, ranging from 13.1% in Oman to 32.6% in Somalia; 5.2% currently used waterpipe, ranging from 0.3% in Morocco to 23.5% in Kuwait. The estimated odds of susceptibility to cigarette smoking were 2.5 (95% CI=1.9, 3.4) times higher for adolescents who used waterpipe in the past month compared with those who did not, controlling for confounders. Estimates were similar when stratified by gender.
CONCLUSIONS: Waterpipe use is associated with susceptibility to cigarette smoking. Study findings identify a novel risk factor for never smokers to initiate smoking and will help the public health community develop and implement policies around waterpipe use prevention.
The lack of research dollars dedicated to understanding the pathophysiology and treatment of psychiatric disorders is a barrier not only to making signiﬁcant medical advances for our patients but also to developing the physician–scientist workforce to fuel those advances.
An Elective in College Mental Health for Training Adult Psychiatry Residents in Young Adult Psychiatry
In this report, we describe a college mental health elective for senior adult psychiatry residents.
Caring for ED patients with suicidal thoughts and behaviors is challenging, given time pressures, boarding of patients waiting for psychiatric beds, and the inherent difficulty in predicting imminent self-harm. However, providers—like patients—should not lose hope: most suicidal crises are short-lived and repeated attempts are not inevitable. Not every ED patient with suicidal thoughts needs inpatient admission or even a mental health consultation, and ED providers should take pride in their skills in caring for this at-risk population.
INTRODUCTION: Previous studies have demonstrated the influence of parental (both mother and father) cigarette smoking on adolescents' cigarette smoking. Little is known, however, about how parental tobacco use is related to waterpipe and dual waterpipe/cigarette use, which is increasing dramatically in the Arab countries.
METHODS: Study data (n = 34 788, N = 6 109 572) were obtained from nationally representative Global Youth Tobacco Surveys in 17 Arab countries. Study outcome was adolescents' tobacco use categorized into none, cigarette smoking only, waterpipe smoking (WPS) only, and dual use. Primary exposure included parental tobacco use categorized into 10 groups-maternal (mother) cigarette smoking only, maternal WPS only, maternal dual use, paternal (father) cigarette smoking only, paternal WPS only, paternal dual use, parental (both mother and father) cigarette smoking only, parental WPS only, parental dual use, and none. Weighted multinomial regression models were conducted to assess the relationships.
RESULTS: Adolescents reported smoking WPS only (5.7%), cigarettes only (2.9%), and dual use (3.5%). Compared to adolescent with no exposure to parental tobacco use, adolescent exposure to parental dual use was associated with significant increase in WPS only (OR = 6.08, 95% CI = 2.38-15.51) and dual use (OR = 3.86, 95% CI = 1.43-10.43). Effect modification of the relationship by adolescents' sex was observed.
CONCLUSIONS: This is the first study to examine adolescent cigarette, waterpipe, and dual use with parental tobacco use. Study findings may help development of cessation interventions targeting parental tobacco use to prevent the rising waterpipe and dual use strain of the global tobacco epidemic.
IMPLICATIONS: (1) Influence of parents' cigarette smoking on adolescents' smoking has been demonstrated in earlier studies, however, little is known about how tobacco use behaviors of mother and father influences an adolescent's cigarette, waterpipe and dual cigarette/waterpipe use. (2) Associations of parental (both mother and father) tobacco use with adolescents' tobacco use differed significantly if the adolescent is a waterpipe smoker or dual user compared to an adolescent cigarette smoker. (3) Adolescents' exposed to their mothers' WPS or dual use were more likely to be a waterpipe smoker or dual user. High likelihood of adolescents' cigarette, waterpipe and dual use is found in homes where parental tobacco use is rampant with both parents smoking either cigarette, waterpipe or both.
The burden of depression in men is high. Current diagnostic criteria may not fully capture men's experience with depression. Descriptions of the heterogeneity in depression among men are lacking. The purpose of the study was to characterize latent subtypes of major depression and changes in these subtypes among men receiving citalopram in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Latent transition analysis was applied to data from 387 men who completed baseline and Week 12 study visits in Level 1 of STAR*D. Items from the self-report version of the Quick Inventory of Depressive Symptomatology were used as indicators of latent depression subtypes. Four statuses were identified at baseline and Week 12. Baseline statuses were Mild (10% of men), Moderate (53%), Severe with Psychomotor Slowing (20%), and Severe with Psychomotor Agitation (17%). At Week 12, the statuses were Symptom Resolution (41%), Mild (36%), Moderate (18%), and Severe with Psychomotor Slowing (5%). Men in the Mild status were most likely to transition to Symptom Resolution (probability = 69%). Men in the Severe with Agitation status were least likely to transition to Symptom Resolution (probability = 0%). This work highlights the need to not focus solely on summary rating scores but to also consider patterns of symptoms when treating depression.
Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells
Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.
Google receives more than 3.5 billion Internet searches daily, and the advertisements on their results pages may provide a unique opportunity to transmit targeted public health information to a large audience. Skin cancer is more common than all other cancers combined, and indoor tanning is a preventable risk factor that accounts for more than 450 000 new malignant neoplasms each year. Tanning bed use remains common, with 1 in 5 adolescents and more than half of college students exposed. Awareness of the dangers of tanning beds is one of the factors that can lead to behavior change. The goals of this study were to examine the volume of tanning bed–related searches on Google and pilot the use of Google’s advertising service for dissemination of skin cancer prevention messages to users entering searches related to tanning beds.
Clinical impact of leukoaraiosis burden and chronological age on neurological deficit recovery and 90-day outcome after minor ischemic stroke
BACKGROUND AND AIMS: Ischemic stroke remains a leading cause of disability, particularly among the elderly, but this association has not been consistently noted among patients with minor stroke. We sought to determine the association of chronological age and leukoaraiosis, which is considered a marker of biological age, with the degree of neurological deficit recovery and 90-day disability after minor ischemic stroke.
METHODS: We retrospectively analyzed 185 patients with a minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score < /=5). Leukoaraiosis severity was graded according to the van Swieten scale. NIHSS was assessed at baseline, discharge, and 90-days. Multivariable linear and ordinal logistic regression analyses were constructed to identify independent predictors of the degree of NIHSS-improvement (DeltaNIHSS) and 90-day outcome as assessed by the modified Rankin Scale (mRS).
RESULTS: Patients with severe leukoaraiosis had attenuated DeltaNIHSS at 90days as compared to patients with none-to-mild leukoaraiosis (p=0.028). After adjustment, leukoaraiosis severity (p < 0.001) but not chronological age (p=0.771) was independently associated with the DeltaNIHSS by day 90. Severe leukoaraiosis (p=0.003, OR 3.1, 95%-CI 1.5-6.4), older age (p=0.001, OR 1.0 95%-CI 1.0-1.1), and admission NIHSS (p < 0.001, OR 1.5, 95%-CI 1.2-1.8) were independent predictors of the 90-day mRS.
CONCLUSION: Leukoaraiosis is a more sensitive predictor for neurological deficit recovery after ischemic stroke than chronological age. Further study is required to establish the specific contribution of leukoaraiosis to functional outcome after minor ischemic stroke beyond its impact on recovery mechanisms.
Detecting Heart Failure Decompensation by Measuring Transthoracic Bioimpedance in the Outpatient Setting: Rationale and Design of the SENTINEL-HF Study
BACKGROUND: Recurrent hospital admissions are common among patients admitted for acute decompensated heart failure (ADHF), but identification of patients at risk for rehospitalization remains challenging. Contemporary heart failure (HF) management programs have shown modest ability to reduce readmissions, partly because they monitor signs or symptoms of HF worsening that appear late during decompensation. Detecting early stages of HF decompensation might allow for immediate application of effective HF therapies, thereby potentially reducing HF readmissions. One of the earliest indicators of HF decompensation is intrathoracic fluid accumulation, which can be assessed using transthoracic bioimpedance.
OBJECTIVE: The SENTINEL-HF study is a prospective observational study designed to test a novel, wearable HF monitoring system as a predictor of HF decompensation among patients discharged after hospitalization for ADHF.
METHODS: SENTINEL-HF tests the hypothesis that a decline in transthoracic bioimpedance, as assessed daily with the Philips fluid accumulation vest (FAV) and transmitted using a mobile phone, is associated with HF worsening and rehospitalization. According to pre-specified power calculations, 180 patients admitted with ADHF are enrolled. Participants transmit daily self-assessments using the FAV-mobile phone dyad for 45 days post-discharge. The primary predictor is the deviation of transthoracic bioimpedance for 3 consecutive days from a patient-specific normal variability range. The ADHF detection algorithm is evaluated in relation with a composite outcome of HF readmission, diuretic up-titration, and self-reported HF worsening (Kansas City Cardiomyopathy Questionnaire) during a 90-day follow-up period. Here, we provide the details and rationale of SENTINEL-HF.
RESULTS: Enrollment in the SENTINEL-HF study is complete and the 90-days follow-up is currently under way. Once data collection is complete, the study dataset will be used to evaluate our ADHF detection algorithm and the results submitted for publication.
CONCLUSION: SENTINEL-HF emerged from our long-term vision that advanced home monitoring technology can improve the management of chronic HF by extending clinical care into patients' homes. Monitoring transthoracic bioimpedance with the FAV may identify patients at risk of recurrent HF decompensation and enable timely preventive measures.
TRIAL REGISTRATION: Clinicaltrials.gov NCT01877369: https://clinicaltrials.gov/ct2/show/NCT01877369 (Archived by WebCite at http://www.webcitation.org/6bDYl0dGy).