The following work demonstrates that paternal diet controls medically important metabolic phenotypes in offspring. We observe transmission of dietary information to the zygote via sperm, and this information evades reprogramming that typically occurs after fertilization. Cytosine methylation is implicated as a major contributor to meiotic epigenetic inheritance in several transgenerational phenomena. Our extensive characterization of the sperm methylome reveals that diet does not significantly affect methylation patterns. However, we find that extensive epivariability in the sperm epigenome makes important contributions to offspring variation. Importantly, coordinate cytosine methylation and copy number changes over the ribosomal DNA locus contributes to variation in offspring metabolism. Thus, rDNA variability acts independently of postadolescent paternal diet to influence offspring metabolism. Therefore, at least two mechanisms exist for epigenetically controlling offspring metabolism: stochastic epivariation and diet acting by an unknown mechanism to further modulate metabolism. This work argues that an offspring's phenotype can no longer be viewed solely as the result of genetic interactions with the developmental environment - the additional influences of paternal environment and inherited epigenetic variability must also be considered. These findings reveal novel contributions to metabolism that could revolutionize how we think about the risk factors for human health and disease.
Objective: To determine trends in research data output, reuse, and sharing of the college of veterinary medicine faculty members at a large academic research institution.
Methods: This bibliographic study was conducted by examining original research articles for indication of the types of data produced, as well as evidence that the authors reused data or made provision for sharing their own data. Findings were recorded in the categories of research type, data type, data reuse, data sharing, author collaboration, and grants/funding and were analyzed to determine trends.
Results: A variety of different data types were encountered in this study, even within a single article, resulting primarily from clinical and laboratory animal studies. All of the articles resulted from author collaboration, both within the University of Illinois at Urbana-Champaign, as well as with researchers outside the institution. There was little indication that data was reused, except some instances where the authors acknowledged that data was obtained directly from a colleague. There was even less indication that the research data was shared, either as a supplementary file on the publisher’s website or by submission to a repository, except in the case of genetic data.
Conclusions: Veterinary researchers are prolific producers and users of a wide variety of data. Despite the large amount of collaborative research occurring in veterinary medicine, this study provided little evidence that veterinary researchers are reusing or sharing their data, except in an informal manner. Wider adoption of data management plans may serve to improve researchers’ data management practices.
Understanding the complex mechanisms to assemble a functional brain demands sophisticated experimental designs. Drosophila melanogaster, a model organism equipped with powerful genetic tools and evolutionarily conserved developmental programs, is ideal for such mechanistic studies. Valuable insights were learned from research in Drosophila ventral nerve cord, such as spatial patterning, temporal coding, and lineage diversification. However, the blueprint of Drosophila cerebrum development remains largely unknown.
Neural progenitor cells, called neuroblasts (NBs), serially and stereotypically produce neurons and glia in the Drosophila cerebrum. Neuroblasts inherit specific sets of early patterning genes, which likely determine their individual identities when neuroblasts delaminate from neuroectoderm. Unique neuroblasts may hence acquire the abilities to differentially interpret the temporal codes and deposit characteristic progeny lineages. We believe resolving this age-old speculation requires a tracing system that links patterning genes to neuroblasts and corresponding lineages, and further allows specific manipulations.
Using modern transgenic systems, one can immortalize transient NB gene expressions into continual labeling of their offspring. Having a collection of knockin drivers that capture endogenous gene expression patterns would open the door for tracing specific NBs and their progenies based on the combinatorial expression of various early patterning genes. Anticipating the need for a high throughput gene targeting system, we created Golic+ (gene targeting during oogenesis with lethality inhibitor and CRISPR/Cas “plus”), which features efficient homologous recombination in cystoblasts and a lethality selection for easy targeting candidate recovery. Using Golic+, we successfully generated T2AGal4 knock-ins for 6 representative early patterning genes, including lab, unpg, hkb, vnd, ind, and msh. They faithfully recapitulated the expression patterns of the targeted genes. After preserving initial NB expressions by triggering irreversible genetic labeling, we revealed the lineages founded by the NBs expressing a particular early patterning gene.
Identifying the neuroblasts and lineages that express a particular early patterning gene should elucidate the genetic origin of neuroblast diversity. We believe such an effort will lead to a deeper understanding of brain development and evolution.
Obesity has been on the rise over the last 30 years, reaching worldwide epidemic proportions. Obesity has been linked to multiple metabolic disorders and co-morbidities such as Type 2 Diabetes Mellitus (T2DM), cardiovascular disease, non-alcoholic steatohepatitis and various cancers. Furthermore, obesity is associated with a chronic state of low-grade inflammation in adipose tissue (AT), and it is thought that insulin resistance (IR) and T2DM is associated with the inflammatory state of AT.
Endothelial cells (ECs) mediate the migration of immune cells into underlying tissues during times of inflammation, including obesity- and cardiovascular disease-associated inflammation. Cytokines and chemoattractants released from inflamed tissues promote EC activation. Upon activation, ECs increase the expression of leukocyte adhesion molecules (LCAMs) including intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), E-selectin (E-sel) and P-selectin (P-sel). Increased expression of these LCAMs and increased infiltration of inflammatory cells such as macrophages, have been linked to IR, diabetes and atherosclerosis in obese individuals. Preliminary data from our lab suggests that lipolysis induced by the β-adrenergic receptor agonist CL 316,243 causes an increase in endothelial LCAM gene expression. In addition, histological analyses show increased content of immune cells within AT after the ECs become activated.
Here, we demonstrate that CL 316,243-induced lipolysis causes infiltration of neutrophils in wild type (WT) but not E-sel knockout (KO) mice. Following EC activation, there was also a marked increase in cytokine gene expression including IL-1β, MCP-1, and TNF-α in an E-sel-dependent manner. In contrast, fasting-induced lipolysis was associated with increased macrophage infiltration into AT in the absence of EC activation in an E-sel-independent manner.
We also examined the role of mitogen activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potential contributor to endothelial activation and atherosclerosis. Here we demonstrate that deletion of MAP4K4 in ECs in vitro diminishes TNF-α-induced EC activation. Additionally, MAP4K4 depletion in primary ECs derived from lungs of mice expressing MAP4K4 shRNA decreases EC activation. Finally, endothelial specific depletion or loss of MAP4K4 reduced atherosclerotic plaque formation in vivo. Taken together, these results highlight the importance of the endothelium in modulating obesity-associated comorbidities. Furthermore, these data implicate endothelial MAP4K4 as a novel regulator of EC activation and consequently AT inflammation and atherosclerosis.
Autophagy delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. Although the regulation and role that autophagy plays in stress, infection, and survival is apparent, its involvement during cell death remains relatively unclear. In this thesis I summarize what is known about the roles autophagy can play in cell death, and the differences between the utilization of autophagy during nutrient deprivation and cell death. Utilizing Drosophila melanogaster as a model system, the roles autophagy plays in both of these contexts can be studied. The goal of this thesis is to provide a better understanding of the regulatory mechanisms that distinguish between autophagy as a survival mechanism and autophagy as a cell death mechanism. From my studies I was able to determine that microRNAs can regulate autophagy in vivo, and that the microRNA miR-14 controls autophagy specifically during the destruction of the larval salivary glands of Drosophila melanogaster. I found that miR-14 regulates autophagy through modulation of IP3 and calcium signaling, and this miR-14 control of IP3 and calcium signaling does not influence the induction of autophagy during nutrient deprivation. Therefore, this knowledge demonstrates how autophagy can be regulated to distinguish its use during cell survival and death providing insight into how autophagy can used to treat diseases.
OBJECTIVE: To describe diagnostic and psychotropic medication prescription characteristics among college students referred by college counseling centers for psychopharmacologic evaluation.
PARTICIPANTS: Participants were 540 college students referred by 6 college counseling centers in Massachusetts between November 2005 and May 2011.
METHODS: Students completed self-report measures of depression, anxiety, suicidal ideation and attempts, and substance use. Information regarding DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) diagnosis, previous history of medication prescription, and current psychotropic medication(s) prescribed by the consulting psychiatrist was obtained from medical records.
RESULTS: Depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) were the most common psychiatric problems identified in students. Half of these students had been prescribed mediation prior to evaluation. Antidepressant medication was the most frequently prescribed medication. A large proportion of students reported previous thoughts of suicide, and 12% had made at least 1 suicide attempt.
CONCLUSIONS: Depression, anxiety, and ADHD are common among students referred by college counseling centers for medication evaluation and treatment.
Personal and parental weight misperception and self-reported attempted weight loss in US children and adolescents, National Health and Nutrition Examination Survey, 2007-2008 and 2009-2010
INTRODUCTION: The objective of our study was to describe perceptions of child weight status among US children, adolescents, and their parents and to examine the extent to which accurate personal and parental perception of weight status is associated with self-reported attempted weight loss.
METHODS: Our study sample comprised 2,613 participants aged 8 to 15 years in the National Health and Nutrition Examination Survey from the 2 most recent consecutive cycles (2007-2008 and 2009-2010). Categories of weight perception were developed by comparing measured to perceived weight status. Multivariable logistic regression analyses were used to examine the association between weight misperception and self-reported attempted weight loss.
RESULTS: Among children and adolescents, 27.3% underestimated and 2.8% overestimated their weight status. Among parents, 25.2% underestimated and 1.1% overestimated their child's weight status. Logistic regression analyses showed that the odds of self-reported attempted weight loss was 9.5 times as high (95% confidence interval [CI]: 3.8-23.6) among healthy-weight children and adolescents who overestimated their weight status as among those who perceived their weight status accurately; the odds of self-reported attempted weight loss were 3.9 (95% CI, 2.4-6.4) and 2.9 (95% CI, 1.8-4.6) times as high among overweight and obese children and adolescents, respectively, who accurately perceived their weight status than among those who underestimated their weight status. Parental misperception of weight was not significantly associated with self-reported attempted weight loss among children and adolescents who were overweight or obese.
CONCLUSION: Efforts to prevent childhood obesity should incorporate education for both children and parents regarding the proper identification and interpretation of actual weight status. Interventions for appropriate weight loss can target children directly because one of the major driving forces to lose weight comes from the child's perception of his or her weight status.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, contributing to increased morbidity and reduced survival through its associations with stroke and heart failure. AF contributes to a four- to fivefold increase in the risk of stroke in the general population and is responsible for 10-15 % of all ischemic strokes. Diagnosis and treatment of AF require considerable health care resources. Current therapies to restore sinus rhythm in AF are suboptimal and are limited either by their pro-arrhythmic effects or by their procedure-related complications. These limitations have necessitated identification of newer therapeutic targets to expand the treatment options. There has been a considerable amount of research interest in investigating the mechanisms of initiation and propagation of AF. Despite extensive research focused on the pathogenesis of AF, a thorough understanding of various pathways mediating initiation and propagation of AF still remains limited. Research efforts focused on the identification of these pathways and molecular mediators have generated a great degree of interest for developing more targeted therapies. This review discusses the potential therapeutic targets and the results from experimental and clinical research investigating these targets.
Evaluation of oral anticoagulants for the extended treatment of venous thromboembolism using a mixed-treatment comparison, meta-analytic approach
PURPOSE: Target-specific oral anticoagulants (apixaban, rivaroxaban, and dabigatran) are widely available for the treatment of venous thromboembolism (VTE). Although analyses comparing these agents to placebo or warfarin exist, direct comparisons of these agents for extended VTE treatment have not been conducted. Therefore, this network meta-analysis aimed to evaluate the efficacy and tolerability of VKA and target-specific oral anticoagulants for extended VTE treatment using a mixed-treatment comparison, meta-analytic approach.
METHODS: A comprehensive literature search of EMBASE and MEDLINE was conducted to identify relevant randomized, controlled trials published in English between 1960 and November 2013. Eligible studies investigated the extended use ( > /=6 months) of oral anticoagulants (apixaban, dabigatran, rivaroxaban, and/or warfarin [conventional or low dose]) and placebo in patients with confirmed VTE. Search terms included extension or extended treatment or therapy, venous thromboembolism (or VTE), deep vein thrombosis (or DVT), pulmonary embolism (or PE), and anticoagulant or anticoagulant agent. Key articles were cross-referenced for additional studies. The efficacy end points evaluated were recurrent VTE or death from any cause, DVT, and nonfatal pulmonary embolism PE. Tolerability end points included major bleeding and nonmajor or clinically relevant bleeding. The data were screened, evaluated, and entered into statistical software to generate direct and indirect comparisons of the various anticoagulants across each study. The data are reported as rate ratios and 95% credible intervals.
FINDINGS: Ten trials were analyzed and aggregated, representing data from > 14,000 patients. With respect to efficacy end points, no statistically significant between-treatment differences in the composite end point of VTE or death, nonfatal PE, or DVT were found. Major bleeding was significantly greater with warfarin versus apixaban (rate ratio, 4.24; credible interval, 1.28-25.0), and the risk for major bleeding varied somewhat with warfarin and greatly with rivaroxaban. The assessment of nonmajor or clinically relevant bleeding did not identify any meaningful differences between these agents.
IMPLICATIONS: The majority of the data represented in this study were derived from noninferiority trials. In the present meta-analysis, efficacy end points in the extended treatment of VTE with apixaban, dabigatran, rivaroxaban, warfarin (conventional and low dose), and placebo were not significantly different. Elevated bleeding risks were identified with rivaroxaban and warfarin; however, the wide credible intervals with rivaroxaban prevent the interpretation of these increased risks.
Photoplethysmograph signal reconstruction based on a novel hybrid motion artifact detection-reduction approach. Part I: Motion and noise artifact detection
Motion and noise artifacts (MNA) are a serious obstacle in utilizing photoplethysmogram (PPG) signals for real-time monitoring of vital signs. We present a MNA detection method which can provide a clean vs. corrupted decision on each successive PPG segment. For motion artifact detection, we compute four time-domain parameters: (1) standard deviation of peak-to-peak intervals (2) standard deviation of peak-to-peak amplitudes (3) standard deviation of systolic and diastolic interval ratios, and (4) mean standard deviation of pulse shape. We have adopted a support vector machine (SVM) which takes these parameters from clean and corrupted PPG signals and builds a decision boundary to classify them. We apply several distinct features of the PPG data to enhance classification performance. The algorithm we developed was verified on PPG data segments recorded by simulation, laboratory-controlled and walking/stair-climbing experiments, respectively, and we compared several well-established MNA detection methods to our proposed algorithm. All compared detection algorithms were evaluated in terms of motion artifact detection accuracy, heart rate (HR) error, and oxygen saturation (SpO2) error. For laboratory controlled finger, forehead recorded PPG data and daily-activity movement data, our proposed algorithm gives 94.4, 93.4, and 93.7% accuracies, respectively. Significant reductions in HR and SpO2 errors (2.3 bpm and 2.7%) were noted when the artifacts that were identified by SVM-MNA were removed from the original signal than without (17.3 bpm and 5.4%). The accuracy and error values of our proposed method were significantly higher and lower, respectively, than all other detection methods. Another advantage of our method is its ability to provide highly accurate onset and offset detection times of MNAs. This capability is important for an automated approach to signal reconstruction of only those data points that need to be reconstructed, which is the subject of the companion paper to this article. Finally, our MNA detection algorithm is real-time realizable as the computational speed on the 7-s PPG data segment was found to be only 7 ms with a Matlab code.
Medication affordability gains following Medicare Part D are eroding among elderly with multiple chronic conditions
Elderly Americans, especially those with multiple chronic conditions, face difficulties paying for prescriptions, which results in worse adherence to and discontinuation of therapy, called cost-related medication nonadherence. Medicare Part D, implemented in January 2006, was supposed to address issues of affordability for prescriptions. We investigated whether the gains in medication affordability attributable to Part D persisted during the six years that followed its implementation. Overall, we found continued incremental improvements in medication affordability in the period 2007-09 that eroded during the period 2009-11. Among elderly beneficiaries with four or more chronic conditions, we observed an increase in the prevalence of cost-related nonadherence from 14.4 percent in 2009 to 17.0 percent in 2011, reversing previous downward trends. Similarly, the prevalence among the sickest elderly of forgoing basic needs to purchase medicines decreased from 8.7 percent in 2007 to 6.8 percent in 2009 but rose to 10.2 percent in 2011. Our findings highlight the need for targeted policy efforts to alleviate the persistent burden of drug treatment costs on this vulnerable population.
Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non-concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores.
Emergency department provider preferences related to clinical practice guidelines for tobacco cessation: a multicenter survey
OBJECTIVES: The objective was to assess current emergency department (ED) provider practices and preferences for tobacco cessation interventions. The ED is an opportune place to initiate smoking cessation interventions. However, little is known about ED provider current practices and preferences for cessation counseling in the ED.
METHODS: This was a survey of ED providers conducted in 2008-2009 (including physicians, nurse practitioners, physician assistants, and nurses), working at least half-time at 10 U.S. academic EDs, regarding adherence to clinical practice guidelines ("5 As") and preferences for cessation interventions/styles. Data analysis occurred in 2012-2013.
RESULTS: The response rate was 64% (800 out of 1,246 completed surveys). Providers reported strongest adherence to asking about patient smoking status, followed by advising, with significant variance by clinical role. Assessing, assisting, and arranging support for patients was low overall. Most frequently used interventions were to provide patients with a list of telephone numbers for stop-smoking counseling (87%), pamphlets on smoking health risks and the benefits of stopping (85%), and referrals to the National Toll-Free Smoker's Quitline (84%). Most providers (80%) were supportive of personally conducting brief (less than 3 minutes) smoking cessation counseling sessions during the ED visit, emphasizing education and encouragement. The least appealing intervention was writing a prescription for nicotine replacement therapies or medications to stop smoking (35%).
CONCLUSIONS: Interventions most likely to be used were brief and delivered with a positive tone and included referral to external resources. The logical next step is to design and test interventions that ED providers find acceptable.
The relation of standardized mental health screening and categorical assessment in detained male adolescents
Having an effective triage tool is an important step toward a careful use of the restricted time and qualified personnel to perform comprehensive psychiatric assessment in juvenile justice settings. The aims of this study were to examine the construct validity of the Massachusetts Youth Screening Inventory-second version (MAYSI-2), and its likelihood to identify youths who might have a psychiatric disorder. Data from up to 781 male adolescents (mean age = 16.73 years) were gathered as part of the standardized mental health screening and assessment in two all-male Youth Detention Centers in the Netherlands. Categorical assessments were based on two structured diagnostic interviews. Sensitivity, specificity, positive and negative predictive values, and the area under the curve were calculated to evaluate the likelihood of the MAYSI-2 to identify youths with a psychiatric disorder. Youths with a disorder scored significantly higher on the corresponding MAYSI-2 subscale than youths without a disorder. In the total sample, 70 % of the youths with a disorder met the Caution cut-off criteria on at least one MAYSI-2 scale, while youths without a psychiatric disorder were very unlikely to meet cut-off criteria for multiple MAYSI-2 scales. Overall, the sensitivity was slightly better when analyses were repeated in groups of youths from various ethnic origins. The findings supported the construct validity of the Dutch MAYSI-2 and suggested that the MAYSI-2 is a valid mental health screening tool that may serve relatively well as a triage tool. Its effectiveness, however, may differ between ethnic groups.
Characteristics, treatment practices, and in-hospital outcomes of older adults hospitalized with acute myocardial infarction
OBJECTIVES: To examine overall and decade-long trends (1999-2009), characteristics, treatment practices, and hospital outcomes in individuals aged 65 and older hospitalized for acute myocardial infarction (AMI) and to describe how these factors varied in the youngest, middle, and oldest-old individuals.
DESIGN: Retrospective cohort study.
SETTING: Population-based Worcester Heart Attack Study.
MEASUREMENTS: Analyses were conducted to examine the sociodemographic and clinical characteristics, cardiac treatments, and hospital outcomes of older adults in three age strata (65-74, 75-84, > /=85).
PARTICIPANTS: The study sample consisted of 3,851 individuals aged 65 and older hospitalized with AMI every other year between 1999 and 2009; 32% were aged 65 to 74, 43% aged 75 to 84, and 25% aged 85 and older. RESULTS: Advancing age was inversely associated with receipt of evidence-based cardiac therapies. After multivariable adjustment, the odds of dying during hospitalization was 1.46 times as high in participants aged 75 to 84 and 1.78 times as high in those aged 85 and older as in those aged 65 to 74. The oldest-old participants had approximately 25% lower odds of a prolonged hospital stay (>3 days) than those aged 65 to 74. Decade-long trends in the principal study outcomes were also examined. Although the oldest-old participants hospitalized for AMI were at the greatest risk of dying, persistent age-related differences were observed in hospital treatment practices. Similar results were observed after excluding participants with a do-not-resuscitate order in their medical records.
CONCLUSION: Although there are persistent disparities in the care and outcomes of older adults hospitalized with AMI, additional studies are needed to delineate the extent to which less-aggressive care reflects individual preferences and appropriate implementation of palliative care approaches.
© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
This paper summarizes recommendations made regarding the National Action Alliance for Suicide Prevention Research Prioritization Task Force's Aspirational Goal 2, to "determine the degree of suicide risk (e.g., imminent, near-term, long-term) among individuals in diverse populations and in diverse settings through feasible and effective screening and assessment approaches." We recommend that researchers shift to using "design for dissemination" principles to maximize both the goodness of fit and validity of screening and assessment measures for a given setting. Three specific recommendations to guide research efforts are made to achieve this shift: (1) the parameters related to each setting, including the logistics, scope of practice, infrastructure, and decision making required, should be identified and used to choose or design screening and assessment instruments that have a good fit; (2) to the greatest feasible extent, technology should be used to support screening and assessment; and (3) researchers should study the best methods for translating validated instruments into routine clinical practice. We discuss the potential barriers to implementing these recommendations and illustrate the paradigm shift within the emergency department setting.
This paper focuses on the National Action Alliance for Suicide Prevention's Research Prioritization Task Force's Aspirational Goal 2 (screening for suicide risk) as it pertains specifically to children, adolescents, and young adults. Two assumptions are forwarded: (1) strategies for screening youth for suicide risk need to be tailored developmentally; and (2) we must use instruments that were created and tested specifically for suicide risk detection and developed specifically for youth. Recommendations for shifting the current paradigm include universal suicide screening for youth in medical settings with validated instruments.
How cardiologists present the benefits of percutaneous coronary interventions to patients with stable angina: a qualitative analysis
IMPORTANCE: Patients with stable coronary artery disease (CAD) attribute greater benefit to percutaneous coronary interventions (PCI) than indicated in clinical trials. Little is known about how cardiologists' presentation of the benefits and risks may influence patients' perceptions.
OBJECTIVES: To broadly describe the content of discussions between patients and cardiologists regarding angiogram and PCI for stable CAD, and to describe elements that may affect patients' understanding.
DESIGN, SETTING, AND PARTICIPANTS: Qualitative content analysis of encounters between cardiologists and patients with stable CAD who participated in the Verilogue Point-of-Practice Database between March 1, 2008, and August 31, 2012. Transcripts in which angiogram and PCI were discussed were retrieved from the database. Patients were aged 44 to 88 years (median, 64 years); 25% were women; 50% reported symptoms of angina; and 6% were taking more than 1 medication to treat angina.
MAIN OUTCOMES AND MEASURES: Results of conventional and directed qualitative content analysis.
RESULTS: Forty encounters were analyzed. Five major categories and subcategories of factors that may affect patients' understanding of benefit were identified: (1) rationale for recommending angiogram and PCI (eg, stress test results, symptoms, and cardiologist's preferences); (2) discussion of benefits (eg, accurate discussion of benefit [5%], explicitly overstated benefit [13%], and implicitly overstated benefit [35%]); (3) discussion of risks (eg, minimization of risk); (4) cardiologist's communication style (eg, humor, teach-back, message framing, and failure to respond to patient questions); and (5) patient and family member contributions to the discussion.
CONCLUSIONS AND RELEVANCE: Few cardiologists discussed the evidence-based benefits of angiogram and PCI for stable CAD, and some implicitly or explicitly overstated the benefits. The etiology of patient misunderstanding is likely multifactorial, but if future quantitative studies support the findings of this hypothesis-generating analysis, modifications to cardiologists' approach to describing the risks and benefits of the procedure may improve patient understanding.
Temporal associations between the different domains of rheumatoid arthritis disease activity and the onset of patient-reported depressive symptoms
BACKGROUND: Depression is a frequently occurring comorbid condition in patients with rheumatoid arthritis (RA), and research into the temporal relationships regarding its onset has mainly focused on functional status. The study aim was to examine temporal associations of the diverse measures of RA disease activity with incident self-reports of depressive symptoms.
METHODS: RA patients from the Consortium of Rheumatology Researchers of North America (CORRONA) registry were utilized. Cox regression was used to assess the lagged time-varying association of RA disease activity with the incident onset of depressive symptoms as measured using a single-item depression question. Predictor variables included joint counts, global assessments, pain, function, serum biomarkers, and composite disease activity. Hazard ratios (HRs) comparing categorical quintiles were estimated with 95 % confidence intervals.
RESULTS: Every metric of disease activity, except inflammatory markers, were significantly associated with the self-reported onset of depressive symptoms. Adjusted HRs comparing fifth quintiles to first quintiles were the following: CDAI = 2.3 [2.1-2.7]; pain = 2.3 [2.0-2.6]; SJC = 1.4 [1.4-1.6]. When examining successive self-reports (two consecutive), the magnitude of the associations greatly increased: CDAI = 3.6 [2.5-5.0].
CONCLUSIONS: The data suggest depressive symptom onset in RA patients is related to measures reported by the patient: pain, functional status, and global disease activity; and measures reported by providers, rather than biological markers. The magnitude of the associations, however, were greater for the patient-reported measures when compared to physician assessments, implying that patients' experience of their disease activity may be a precipitating factor of depression onset.
Disclosure of adverse events in the United States and Canada: an update, and a proposed framework for improvement
There is consensus that physicians, health professionals and health care organizations should discuss harm that results from health care delivery (adverse events), including the reasons for harm, with patients and their families. Thought leaders and policy makers in the USA and Canada support this goal. However, there are gaps in both countries between patients and physicians in their attitudes about how errors should be handled, and between disclosure policies and their implementation in practice. This paper reviews the state of disclosure policy and practice in the two countries, and the barriers to full disclosure. Important barriers include fear of consequences, attitudes about disclosure, lack of skill and role models, and lack of peer and institutional support. The paper also describes the problem of the second victim, a corollary of disclosure whereby health care workers are also traumatized by the same events that harm patients. The presence of multiple practical and personal barriers to disclosure suggests the need for a comprehensive solution directed at multiple levels of the health care system, including health departments, institutions, local managers, professional staff, patients and families, and including legal, health system and local institutional support. At the local level, implementation could be based on a translating-evidence-into-practice framework. Applying this framework would involve the formation of teams, training, measurement and identification of local barriers to achieving universal disclosure of adverse events. Significance for public healthIt is inevitable that some patients will be harmed rather than helped by health care. There is consensus that patients and their families must be told about these harmful events. However, there are gaps between patient and physician attitudes about how errors should be handled, and between disclosure policies and their implementation. There are important barriers that impede disclosure, including fear of consequences, attitudes about disclosure, lack of skill, and lack of institutional support. A related problem is that of the second victim, whereby health care workers are traumatized by the same harmful events. This can impair their performance and further compromise safety. The problem is unlikely to be solved by focusing solely on increasing disclosure. A comprehensive solution is needed, directed at multiple levels of the health care system, including health departments, institutions, local managers, professional staff, patients and families, and including legal, health system and local institutional support.