Encouragement to Increase the Use of Psychosocial Skills in the Diagnosis and Therapy of Patients With Functional Dysphonia.

Clinicians believe that psychosocial factors play a causal role in the etiology of many forms of functional dysphonia (FD). But for decades, all attempts to confirm such causation have failed. This paper aims to show the logic of this failure, to discuss the possibilities of employing psychology in therapy nonetheless, and to encourage clinicians to use their psychosocial knowledge and skills. The failure to confirm psychic and social factors as causal in the etiology of FD is basically a consequence of a principal shortcoming of evidence-based medicine (EBM). As the gold standard for validity, reliability, and objectivity in medical research, EBM is based on calculability and hence the processing of quantitative data. But life paths and life situations are best or sometimes only expressible in qualitative, experiential, and idiographic terms. Thus EBM-guided evaluation undervalues most psychosocial studies. This report of an experienced multidisciplinary voice team proposes alternative pathways for integrating psychosocial knowledge into the diagnosis and the treatment of FD. The difference between the fields of activity of psychotherapists and speech-language pathologists is discussed, and the latter group is shown the potential benefits of using more of their psychosocial knowledge and skills.

Cost-effectiveness of peer role play and standardized patients in undergraduate communication training.

BACKGROUND The few studies directly comparing the methodological approach of peer role play (RP) and standardized patients (SP) for the delivery of communication skills all suggest that both methods are effective. In this study we calculated the costs of both methods (given comparable outcomes) and are the first to generate a differential cost-effectiveness analysis of both methods. METHODS Medical students in their prefinal year were randomly assigned to one of two groups receiving communication training in Pediatrics either with RP (N = 34) or 19 individually trained SP (N = 35). In an OSCE with standardized patients using the Calgary-Cambridge Referenced Observation Guide both groups achieved comparable high scores (results published). In this study, corresponding costs were assessed as man-hours resulting from hours of work of SP and tutors. A cost-effectiveness analysis was performed. RESULTS Cost-effectiveness analysis revealed a major advantage for RP as compared to SP (112 vs. 172 man hours; cost effectiveness ratio .74 vs. .45) at comparable performance levels after training with both methods. CONCLUSIONS While both peer role play and training with standardized patients have their value in medical curricula, RP has a major advantage in terms of cost-effectiveness. This could be taken into account in future decisions.

Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.

The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electric impulse. Emerging evidence over the past 20 years strongly suggests that the normal electric function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, post-translational modification, turnover, function, and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium, and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electric function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy.

Low correlation between self-report and medical record documentation of urinary tract infection symptoms.

BACKGROUND Correlations between symptom documentation in medical records and patient self-report (SR) vary depending on the condition studied. Patient symptoms are particularly important in urinary tract infection (UTI) diagnosis, and this correlation for UTI symptoms is currently unknown. METHODS This is a cross-sectional survey study in hospitalized patients with Escherichia coli bacteriuria. Patients were interviewed within 24 hours of diagnosis for the SR of UTI symptoms. We reviewed medical records for UTI symptoms documented by admitting or treating inpatient physicians (IPs), nurses (RNs), and emergency physicians (EPs). The level of agreement between groups was assessed using Cohen κ coefficient. RESULTS Out of 43 patients, 34 (79%) self-reported at least 1 of 6 primary symptoms. The most common self-reported symptoms were urinary frequency (53.5%); retention (41.9%); flank pain, suprapubic pain, and fatigue (37.2% each); and dysuria (30.2%). Correlation between SR and medical record documentation was slight to fair (κ, 0.06-0.4 between SR and IPs and 0.09-0.5 between SR and EDs). Positive agreement was highest for dysuria and frequency. CONCLUSION Correlation between self-reported UTI symptoms and health care providers' documentation was low to fair. Because medical records are a vital source of information for clinicians and researchers and symptom assessment and documentation are vital in distinguishing UTI from asymptomatic bacteriuria, efforts must be made to improve documentation.

Investigation of arterial spin labeling MRI for quantitative cerebral blood flow measurement

Arterial spin labeling (ASL) is a technique for noninvasively measuring cerebral perfusion using magnetic resonance imaging. Clinical applications of ASL include functional activation studies, evaluation of the effect of pharmaceuticals on perfusion, and assessment of cerebrovascular disease, stroke, and brain tumor. The use of ASL in the clinic has been limited by poor image quality when large anatomic coverage is required and the time required for data acquisition and processing. This research sought to address these difficulties by optimizing the ASL acquisition and processing schemes. To improve data acquisition, optimal acquisition parameters were determined through simulations, phantom studies and in vivo measurements. The scan time for ASL data acquisition was limited to fifteen minutes to reduce potential subject motion. A processing scheme was implemented that rapidly produced regional cerebral blood flow (rCBF) maps with minimal user input. To provide a measure of the precision of the rCBF values produced by ASL, bootstrap analysis was performed on a representative data set. The bootstrap analysis of single gray and white matter voxels yielded a coefficient of variation of 6.7% and 29% respectively, implying that the calculated rCBF value is far more precise for gray matter than white matter. Additionally, bootstrap analysis was performed to investigate the sensitivity of the rCBF data to the input parameters and provide a quantitative comparison of several existing perfusion models. This study guided the selection of the optimum perfusion quantification model for further experiments. The optimized ASL acquisition and processing schemes were evaluated with two ASL acquisitions on each of five normal subjects. The gray-to-white matter rCBF ratios for nine of the ten acquisitions were within ±10% of 2.6 and none were statistically different from 2.6, the typical ratio produced by a variety of quantitative perfusion techniques. Overall, this work produced an ASL data acquisition and processing technique for quantitative perfusion and functional activation studies, while revealing the limitations of the technique through bootstrap analysis. ^

Impact of a modified dietary plan on the health related quality of life of minority participants in the Women's Healthy Eating and Living (WHEL) Study

Advances in medical technology, in genetics, and in clinical research have led to early detection of cancer, precise diagnosis, and effective treatment modalities. Decline in cancer incidence and mortality due to cancer has led to increased number of long-term survivors. However, the ethnic minority population has not experienced this decline and still continues to carry a disparate proportion of the cancer burden. Majority of the clinical research including survivorship studies have recruited and continue to recruit a convenient sample of middle- to upper-class Caucasian survivors. Thus, minorities are underrepresented in cancer research in terms of both clinical studies and in health related quality of life (HRQOL) studies. ^ Life style and diet have been associated with increased risk of breast cancer. High vegetable low fat diet has been shown to reduce recurrence of breast cancer and early death. The Women's Healthy Eating and Living Study is an ongoing multi-site randomized controlled trial that is evaluating the high-vegetable low fat diet in reducing the recurrence of breast cancer and early death. The purpose of this dissertation was to (1) compare the impact of the modified diet on the HRQOL during the first 12-month period on specific Minorities and matched Caucasians; (2) identify predictors that significantly impact the HRQOL of the study participants; and (3) using the structural equation modeling assess the impact of nutrition on the HRQOL of the intervention group participants. Findings suggest that there are no significant differences in change in HRQOL between Minorities and Caucasians; between Minorities in the intervention group and those in the comparison group; and between women in the intervention group and those in the comparison group. Minority indicator variable and Intervention/Comparison group indicator variable were not found to be good predictors of HRQOL. Although the structural equation models suggested viable representation of the relationship between the antecedent variables, the mediating variables and the two outcome variables, the impact of nutrition was not statistically significant to be included in the model. This dissertation, by analyzing the HRQOL of minorities in the WHEL Study, attempted to add to the knowledge base specific to minority cancer survivors. ^

Preclinical modeling of multi-drug cancer therapies

Anticancer drugs typically are administered in the clinic in the form of mixtures, sometimes called combinations. Only in rare cases, however, are mixtures approved as drugs. Rather, research on mixtures tends to occur after single drugs have been approved. The goal of this research project was to develop modeling approaches that would encourage rational preclinical mixture design. To this end, a series of models were developed. First, several QSAR classification models were constructed to predict the cytotoxicity, oral clearance, and acute systemic toxicity of drugs. The QSAR models were applied to a set of over 115,000 natural compounds in order to identify promising ones for testing in mixtures. Second, an improved method was developed to assess synergistic, antagonistic, and additive effects between drugs in a mixture. This method, dubbed the MixLow method, is similar to the Median-Effect method, the de facto standard for assessing drug interactions. The primary difference between the two is that the MixLow method uses a nonlinear mixed-effects model to estimate parameters of concentration-effect curves, rather than an ordinary least squares procedure. Parameter estimators produced by the MixLow method were more precise than those produced by the Median-Effect Method, and coverage of Loewe index confidence intervals was superior. Third, a model was developed to predict drug interactions based on scores obtained from virtual docking experiments. This represents a novel approach for modeling drug mixtures and was more useful for the data modeled here than competing approaches. The model was applied to cytotoxicity data for 45 mixtures, each composed of up to 10 selected drugs. One drug, doxorubicin, was a standard chemotherapy agent and the others were well-known natural compounds including curcumin, EGCG, quercetin, and rhein. Predictions of synergism/antagonism were made for all possible fixed-ratio mixtures, cytotoxicities of the 10 best-scoring mixtures were tested, and drug interactions were assessed. Predicted and observed responses were highly correlated (r2 = 0.83). Results suggested that some mixtures allowed up to an 11-fold reduction of doxorubicin concentrations without sacrificing efficacy. Taken together, the models developed in this project present a general approach to rational design of mixtures during preclinical drug development. ^

The population health performance of medical students at two medical schools

Public Health and medicine are complimentary disciplines dedicated to the health and well-being of humankind. Worldwide, medical school accreditation bodies require the inclusion of population health in medical education. In 2003, the Institutes of Medicine (IOM) recommended that all medical students receive basic public health training in population-based prevention. The purpose of this study was to (1) examine the public health clinical performance of third-year medical students at two independent medical schools, (2) compare the public health clinical practice performance of the schools, and (3) identify underlying predictors of high and low public health clinical performance at one of the medical schools. ^ This study is unique in its analysis and report of observed medical student public health clinical practices. The cohort consisted of 751 third-year medical students who completed a required clinical performance exam using trained standardized patients. Medical student performance scores on 24 consensus public health items derived from nine patient cases were analyzed.^ The analysis showed nearly identical results for both medical schools at the 60%, 65%, and 70% pass rate. Students performed poorly on items associated with prevention, behavioral science, and surveillance. Factors associated with high student performance included being from an underrepresented minority, matching to a primary care residency, and high class ranking. A review of medical school curriculum at both schools revealed a lack of training in four public health domains. Nationally, 32% of medical students reported inadequate training in public health in the year 2006.^ These findings suggest more dedicated teaching time for public health domains is needed at the medical schools represented in this study. Finally, more research is needed to assess attainment of public health knowledge and skills for medical students nationwide if we are to meet the recommendations of the IOM. ^

Spirituality of Thai Buddhists with chronic cardiovascular disease

Background. Advances in medical technology contribute to the survival rate of a growing number of persons with chronic illnesses. Individuals with chronic cardiovascular disease (chronic CVD) are among other chronically ill persons who add to the need for healthcare services. They need to cope and live with the chronic conditions and find a new balance to make sense of their lives. Thai Buddhists with chronic CVD may use their religious resources to cope with their illnesses because religious beliefs are reflected in patterns of living. The aims of the study were to: (a) explore how Thai Buddhists with chronic CVD construct the spiritual aspects of the illness experience, (b) explore how Thai Buddhists with chronic CVD may use their spiritual/religious resources as a means of coping with the illness, and (c) explore the impacts of spiritual/religious beliefs and/or practices on the daily lives of Thai Buddhists with chronic CVD. ^ Methods. Ethnography was employed and data were collected from December 1, 2007 to May 31, 2008 using in-depth interviews with 20 participants. Field notes were also recorded. ^ Findings. Three categories emerged from the study data: set of spiritual and biomedical beliefs and practices, integrated meanings, and positive consequences of the integration of spiritual and biomedical beliefs and practices. ^ Conclusions. The findings of the study suggest the importance of understanding and integrating spiritual needs into care of patients with chronic CVD. The findings revealed that the participants constructed ideas of their illness and meanings for living and coping with the illness, and integrated spiritual and biomedical beliefs and practices, resulting in positive outcomes. Further research could test interventions which facilitate such coping; for example, using reflective thinking and group support. Other studies might explore how age affects Buddhist views of the illness. ^

Ascertainment, meta-analysis and reporting of adverse reactions in clinical trials of antibiotics

The ascertainment and analysis of adverse reactions to investigational agents presents a significant challenge because of the infrequency of these events, their subjective nature and the low priority of safety evaluations in many clinical trials. A one year review of antibiotic trials published in medical journals demonstrates the lack of standards in identifying and reporting these potentially fatal conditions. This review also illustrates the low probability of observing and detecting rare events in typical clinical trials which include fewer than 300 subjects. Uniform standards for ascertainment and reporting are suggested which include operational definitions of study subjects. Meta-analysis of selected antibiotic trials using multivariate regression analysis indicates that meaningful conclusions may be drawn from data from multiple studies which are pooled in a scientifically rigorous manner. ^

Percutaneous transluminal coronary angioplasty and coronary events in a biethnic Texas community, 1985--1990

The relationship between change in myocardial infarction (MI) mortality rate (ICD codes 410, 411) and change in use of percutaneous transluminal coronary angioplasty (PTCA), adjusted for change in hospitalization rates for MI, and for change in use of aortocoronary bypass surgery (ACBS) from 1985 through 1990 at private hospitals was examined in the biethnic community of Nueces County, Texas, site of the Corpus Christi Heart Project, a major coronary heart disease (CHD) surveillance program. Age-adjusted rates (per 100,000 persons) were calculated for each of these CHD events for the population aged 25 through 74 years and for each of the four major sex-ethnic groups: Mexican-American and Non-Hispanic White women and men. Over this six year period, there were 541 MI deaths, 2358 MI hospitalizations, 816 PTCA hospitalizations, and 920 ACBS hospitalizations among Mexican-American and Non-Hispanic White Nueces County residents. Acute MI mortality decreased from 24.7 in the first quarter of 1985 to 12.1 in the fourth quarter of 1990, a 51.2% decrease. All three hospitalization rates increased: The MI hospitalization rates increased from 44.1 to 61.3, a 38.9% increase, PTCA use increased from 7.1 to 23.2, a 228.0% increase, and ACBS use increased from 18.8 to 29.5, a 56.6% increase. In linear regression analyses, the change in MI mortality rate was negatively associated with the change in PTCA use (beta = $-$.266 $\pm$.103, p = 0.017) but was not associated with the changes in MI hospitalization rate and in ACBS use. The results of this ecologic research support the idea that the increasing use of PTCA, but not ACBS, has been associated with decreases in MI mortality. The contrast in associations between these two revascularization procedures and MI mortality highlights the need for research aimed at clarifying the proper roles of these procedures in the treatment of patients with CHD. The association between change in PTCA use and change in MI mortality supports the idea that some changes in medical treatment may be partially responsible for trends in CHD mortality. Differences in the use of therapies such as PTCA may be related to differences between geographical sites in CHD rates and trends. ^

HEALTH CARE COST INCREASES IN METROPOLITAN AREAS

The research project is an extension of the economic theory to the health care field and health care research projects evaluating the influence of demand and supply variables upon medical care inflation. The research tests a model linking the demographic and socioeconomic characteristics of the population, its community case mix, and technology, the prices of goods and services other than medical care, the way its medical services are delivered and the health care resources available to its population to different utilization patterns which, consequently, lead to variations in health care prices among metropolitan areas. The research considers the relationship of changes in community characteristics and resources and medical care inflation.^ The rapidly increasing costs of medical care have been of great concern to the general public, medical profession, and political bodies. Research and analysis of the main factors responsible for the rate of increase of medical care prices is necessary in order to devise appropriate solutions to cope with the problem. An understanding of the community characteristics and resources-medical care costs relationships in the metropolitan areas potentially offers guidance in individual plan and national policy development.^ The research considers 145 factors measuring community milieu (demographic, social, educational, economic, illness level, prices of goods and services other than medical care, hospital supply, physicians resources and techological factors). Through bivariate correlation analysis, the number of variables was reduced to a set of 1 to 4 variables for each cost equation. Two approaches were identified to track inflation in the health care industry. One approach measures costs of production which accounts for price and volume increases. The other approach measures price increases. One general and four specific measures were developed to represent each of the major approaches. The general measure considers the increase on medical care prices as a whole and the specific measures deal with hospital costs and physician's fees. The relationships among changes in community characteristics and resources and health care inflation were analyzed using bivariate correlation and regression analysis methods. It has been concluded that changes in community characteristics and resources are predictive of hospital costs and physician's fees inflation, but are not predictive of increases in medical care prices. These findings provide guidance in the formulation of public policy which could alter the trend of medical care inflation and in the allocation of limited Federal funds.^

Evaluation of Knowledge Regarding Diagnostic Strategies for Genetic Diseases in Select Residents

Genetics education for physicians has been a popular publication topic in the United States and in Europe for over 20 years. Decreasing numbers of medical genetics professionals and an increasing volume of genetic information has created a dire need for increased genetics training in medical school and in clinical practice. This study aimed to assess how well pediatrics-focused primary care physicians apply their general genetics knowledge to clinical genetic testing using scenario-based questions. We chose to specifically focus on knowledge of the diagnostic applicability of Chromosomal Microarray (CMA) technology in pediatrics because of its recent recommendation by the International Standard Cytogenomic Array (ISCA) Consortium as a first-tier genetic test for individuals with developmental disabilities and/or congenital anomalies. Proficiency in ordering baseline genetic testing was evaluated for eighty-one respondents from four pediatrics-focused residencies (categorical pediatrics, pediatric neurology, internal medicine/pediatrics, and family practice) at two large residency programs in Houston, Texas. Similar to other studies, we found an overall deficit of genetic testing knowledge, especially among family practice residents. Interestingly, residents who elected to complete a genetics rotation in medical school scored significantly better than expected, as well as better than residents who did not elect to complete a genetics rotation. We suspect that the insufficient knowledge among physicians regarding a baseline genetics work-up is leading to redundant (i.e. concurrent karyotype and CMA) and incorrect (i.e. ordering CMA to detect achondroplasia) genetic testing and is contributing to rising health care costs in the United States. Our results provide specific teaching points upon which medical schools can focus education about clinical genetic testing and suggest that increased collaboration between primary care physicians and genetics professionals could benefit patient health care overall.