Psychometric Testing of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale Using Pooled Chemotherapy-Induced Peripheral Neuropathy Outcome Measures Standardization and Alliance for Clinical Trials in Oncology A151408 Study Data.

BACKGROUND: No criterion-standard patient-reported outcome measure of chemotherapy-induced peripheral neuropathy (CIPN) exists. OBJECTIVES: The aims of this study were to reevaluate the sensitivity, reliability, and validity of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (QLQ-CIPN20) measure and suggest possible revisions that could strengthen it. METHODS: Cross-sectional QLQ-CIPN20 data from 8 European countries (n = 271) were pooled with data from 4 North American multisite CIPN intervention trials (n = 884). The combined sample (N = 1155) included patients with varied cancer diagnoses who had received neurotoxic chemotherapy. Item score ranges, Cronbach's α, and exploratory factor analysis were used to evaluate sensitivity, internal consistency, and structural validity. RESULTS: Individual item mean scores ranged from 1.21 to 2.34 (SD range, 0.55-1.17). All item scores encompassed the entire 1 to 4 range. We recommend that 4 items be removed because of low item-item score correlations (r < 0.30). On the basis of the remaining 16 items, 88% of the variance was explained by 2 factors whose Cronbach's α coefficients were .90 and .85. However, items lacked conceptual alignment with previously published factor structures. CONCLUSION: Using a large, diverse sample of European and North American participants, the reduced 16-item QLQ-CIPN20 is sensitive and internally consistent. However, factor analysis results revealed an unstable factor structure. IMPLICATIONS FOR PRACTICE: The use of a reliable, valid, and sensitive criterion-standard QLQ-CIPN20 variant in clinical practice settings could improve function, quality of life, and CIPN symptom control by facilitating patient reporting and thereby clinician awareness of this underrecognized consequence of cancer therapy.

Editorial (Spring) Board? Gender Composition in High-impact General Surgery Journals Over 20 Years.

OBJECTIVE: To quantify gender composition of 10 high-impact general surgery journals, delineate how board composition has changed over time, and evaluate qualification metrics by gender. BACKGROUND: Underrepresentation of women on editorial boards may contribute to the gender-based achievement gap in surgery. METHODS: We performed a cross-sectional analysis of the editorial board gender composition among 10 high-impact general surgery journals in 1997, 2007, and 2017. Univariate and multivariate regression analyses were used to assess differences in editors' H-indices, academic rank, and number of advanced degrees. Differences in editor turnover and multiple board positions were evaluated for each time interval. RESULTS: Over 20 years, the proportion of women on editorial boards increased from 5% to 19%. After controlling for time since board certification, no differences between men and women's number of advanced degrees, H-indices, or academic rank remained significant. Women and men were equally likely to hold multiple board positions (1997 P = 0.74; 2007 P = 0.42; 2017 P = 0.69), but men's editorial board tenure was longer across each time interval (1997-2007 P = 0.003; 2007-2017 P < 0.001; 1997-2017 P = 0.01). CONCLUSIONS: Women surgeons have a small but growing presence on surgical editorial boards, and gender-based qualification differences are likely attributable to practice length. Men's longer tenure on editorial boards may drive some of the observed disparity by limiting new appointment opportunities. Strategies such as imposing term limits or instituting merit-based performance reviews may help editorial boards capture the field's changing demographics.

Interruptions In Private Health Insurance And Outcomes In Adults With Type 1 Diabetes: A Longitudinal Study.

Type 1 diabetes mellitus, which often originates during childhood, is a lifelong disease that requires intensive daily medical management. Because health care services are critical to patients with this disease, we investigated the frequency of interruptions in private health insurance, and the outcomes associated with them, for working-age adults with type 1 diabetes in the United States in the period 2001-15. We designed a longitudinal study with a nested self-controlled case series, using the Clinformatics Data Mart Database. The study sample consisted of 168,612 adults ages 19-64 with type 1 diabetes who had 2.6 mean years of insurance coverage overall. Of these adults, 24.3 percent experienced an interruption in coverage. For each interruption, there was a 3.6 percent relative increase in glycated hemoglobin. The use of acute care services was fivefold greater after an interruption in health insurance compared to before the interruption and remained elevated when stratified by age, sex, or diabetic complications. An interruption was associated with lower perceived health status and lower satisfaction with life. We conclude that interruptions in private health insurance are common among adults with type 1 diabetes and have serious consequences for their well-being.

Communication With Physicians as a Mediator in the Relationship Between the Nursing Work Environment and Select Nurse Outcomes in Jordan.

PURPOSE: To test whether communication mediated relationships among nurses' work environments and nurse outcomes of job satisfaction and intent to stay. DESIGN: This study used a cross-sectional, quantitative survey design to query 650 nurses who worked in three hospitals in Jordan. METHODS: We used Arabic versions of valid, reliable instruments measuring the nursing work environment, nurse perceptions of communication with physicians, intent to stay, and job satisfaction. Mediation analysis was used to test hypotheses. FINDINGS: A total of 582 questionnaires were returned (89.5% response rate). Nurse perceptions of communication with physicians mediated the relationship between the nursing work environment and job satisfaction in medical, surgical, and critical care units. Nurse perceptions of communication with physicians mediated the relationship between the nursing work environment and intent to stay in all but maternity and "other" units. CONCLUSIONS: Depending on the nurse outcome, communication was a significant mediator for various unit types. These results may be related to the type of work that is done in each unit and the influence of patient care. Communication is one of many mechanisms that can specify how a positive nursing work environment can contribute to nurses' job satisfaction and intent to stay. CLINICAL RELEVANCE: A potential solution to the nursing shortage in Jordan emerges by identifying communication with physicians as a mediator in the relationship between the work environment and selected nurse outcomes.

Exploring chronic disease in Bolivia: A cross-sectional study in La Paz.

PURPOSE: This study seeks to develop an understanding that can guide development of programs to improve health and care for individuals with Non-Communicable Diseases (NCDs) in La Paz, Bolivia, where NCDs are prevalent and primary care systems are weak. This exploratory investigation examines the characteristics of chronic disease patients in the region, key health related behaviors, and their perceptions of the care that they receive. The longer-term goal is to lay groundwork for interventional studies based on the principles of the Chronic Care Model (CCM). SUBJECTS AND METHODS: The study is based on two surveys of adults (> 18 years old) administered in 2014 in La Paz, Bolivia. A total of 1165 adult patients participated in the first screening survey. A post-screening second survey, administered only on those who qualified based on Survey 1, collected more detailed information about the subjects' general health and health related personal circumstances, several health behaviors, health literacy, and their perceptions of care received. A final data set of 651 merged records were used for analysis. RESULTS: Characteristic of a low-income country, the majority of participants had low levels of education, income, health literacy and high rates of under/unemployment. Nearly 50% of participants reported 2 or more NCDs. Seventy-four percent (74%) of respondents reported low levels of medication adherence and 26% of the population was found to have an undiagnosed depressive disorder. Overall, the perception of care quality was low (60%), particularly in those under the age of 45. Significant relationships emerged between several sociodemographic characteristics, health behaviors, and perceptions that have major implications for improving NCD care in this population. CONCLUSIONS: These findings illustrate some of the challenges facing low-income countries where reversing the tide of NCDs is of great importance. The prevalence of NCDs coupled with challenging social determinants of health, poor medication adherence, low health literacy, and perceptions of low quality of healthcare highlight several areas of opportunity for intervention.

Impact of Clinical Guidelines on Voiding Cystourethrogram Use and Vesicoureteral Reflux Incidence.

PURPOSE: To prevent over diagnosis and overtreatment of vesicoureteral reflux the 2007 NICE (National Institute for Health and Care Excellence) and 2011 AAP (American Academy of Pediatrics) guidelines recommended against routine voiding cystourethrograms in children presenting with first febrile urinary tract infections. The impact of these guidelines on clinical practice is unknown. MATERIALS AND METHODS: Using an administrative claims database (Clinformatics™ Data Mart) children who underwent voiding cystourethrogram studies or had a diagnosis of vesicoureteral reflux between 2001 and 2015 were identified. The cohort was divided into children age 0 to 2 and 3 to 10 years. Single and multiple group interrupted time series analyses (difference-in-difference) were performed with the guidelines as intervention points. The incidence of vesicoureteral reflux was compared across each period. RESULTS: Of the 51,649 children who underwent voiding cystourethrograms 19,422 (38%) were diagnosed with vesicoureteral reflux. In children 0 to 2 years old voiding cystourethrogram use did not decrease after the 2007 NICE guidelines were announced (-0.37, 95% CI -1.50 to 0.77, p = 0.52) but did decrease significantly after the 2011 AAP guidelines were announced (-2.00, 95% CI -3.35 to -0.65, p = 0.004). Among children 3 to 10 years old voiding cystourethrogram use decreased during the entire study period. There was a decrease in the incidence of vesicoureteral reflux in both groups that mirrored patterns of voiding cystourethrogram use. CONCLUSIONS: The 2011 AAP guidelines led to a concurrent decrease in voiding cystourethrogram use and incidence of vesicoureteral reflux among children 0 to 2 years old. Further studies are needed to assess the risks and benefits of reducing the diagnosis of vesicoureteral reflux in young children.

Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study.

BACKGROUND: While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0-19 years) to that of adults (20-64 years). METHODS: In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001-2015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. RESULTS: Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 10-14 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.30-1.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.1-2.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.0-5.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.6-4.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 to 2015 (-1.3%/year; 95% CI -2.3% to -0.4%; P = 0.007). Greater percentages of cases were diagnosed in January, July, and August for both youth and adults. The number of new cases of type 1 diabetes (ages 0-64 years) in the United States is estimated at 64,000 annually (27,000 cases in youth and 37,000 cases in adults). CONCLUSIONS: There are more new cases of type 1 diabetes occurring annually in the United States than previously recognized. The increase in incidence rates in youth, but not adults, suggests that the precipitating factors of youth-onset disease may differ from those of adult-onset disease.

Improving health literacy through group antenatal care: a prospective cohort study.

BACKGROUND: To examine whether exposure to group antenatal care increased women's health literacy by improving their ability to interpret and utilize health messages compared to women who received standard, individual antenatal care in Ghana. METHODS: We used a prospective cohort design. The setting was a busy urban district hospital in Kumasi, the second most populous city in Ghana. Pregnant women (N = 240) presenting for their first antenatal visit between 11 and 14 weeks gestation were offered participation in the study. A 27% drop-out rate was experienced due to miscarriage, transfer or failure to return for follow-up visits, leaving 184 women in the final sample. Data were collected using an individual structured survey and medical record review. Summary statistics as well as two sample t-tests or chi-square were performed to evaluate the group effect. RESULTS: Significant group differences were found. Women participating in group care demonstrated improved health literacy by exhibiting a greater understanding of how to operationalize health education messages. There was a significant difference between women enrolled in group antenatal care verses individual antenatal care for preventing problems before delivery, understanding when to access care, birth preparedness and complication readiness, intent to use a modern method of family planning postpartum, greater understanding of the components of breastfeeding and lactational amenorrhea for birth spacing, and intent for postpartum follow-up. CONCLUSION: Group antenatal care as compared to individual care offers an opportunity to increase quality of care and improve maternal and newborn outcomes. Group antenatal care holds the potential to increase healthy behaviors, promote respectful maternity care, and generate demand for services. Group ANC improves women's health literacy on how to prevent and recognize problems, prepare for delivery, and care for their newborn.

Effectiveness of implementing a dyadic psychoeducational intervention for cancer patients and family caregivers.

PURPOSE: This study examined the effectiveness, feasibility, and satisfaction with implementation of the FOCUS program in two US Cancer Support Community affiliates in Ohio and California as well as the cost to deliver the program. FOCUS is an evidence-based psychoeducational intervention for dyads (cancer patients and caregivers). METHODS: A pre-post-intervention design was employed. Eleven, five-session Focus programs were delivered by licensed professionals in a small group format (three-four dyads/group) to 36 patient-caregiver dyads. An Implementation Training Manual, a FOCUS Intervention Protocol Manual, and weekly conference calls were used to foster implementation. Participants completed questionnaires prior to and following completion of each five-session FOCUS program to measure primary (emotional distress, quality of life) and secondary outcomes (benefits of illness, self-efficacy, and dyadic communication). Enrollment and retention rates and fidelity to FOCUS were used to measure feasibility. Cost estimates were based on time and median hourly wages. Repeated analysis of variance was used to analyze the effect of FOCUS on outcomes for dyads. Descriptive statistics were used to examine feasibility, satisfaction, and cost estimates. RESULTS: FOCUS had positive effects on QOL (p = .014), emotional (p = .012), and functional (p = .049) well-being, emotional distress (p = .002), benefits of illness (p = .013), and self-efficacy (p = .001). Intervention fidelity was 85% with enrollment and retention rates of 71.4 and 90%, respectively. Participants were highly satisfied. Cost for oversight and delivery of the five-session FOCUS program was $168.00 per dyad. CONCLUSIONS: FOCUS is an economic and effective intervention to decrease distress and improve the quality of life for dyads.

Efficacy of a biobehavioral intervention for hot flashes: a randomized controlled pilot study.

OBJECTIVE: The need for effective nonhormonal treatments for hot flash management without unwanted side effects continues. The primary aim of this pilot study was to evaluate the effect of combining a nonhormonal pharmacologic agent with a behavioral treatment for hot flash reduction. METHODS: Seventy-one postmenopausal women were randomized to one of four groups: venlafaxine 75 mg + hypnosis (VH) versus venlafaxine 75 mg + sham hypnosis (VSH) versus a placebo pill + hypnosis (PH) versus placebo pill + sham hypnosis (PSH). Women recorded hot flash severity and frequency in a daily diary, in real time. The intrapatient difference in hot flash score (frequency × severity) at 8 weeks was analyzed using a General Estimating Equation model, using VSH as the referent arm, controlling for baseline hot flashes. RESULTS: The active arms including PH or VH were not statistically significantly different than VSH (P = 0.34, P = 0.05, respectively). Women in each active arm reported hot flash reductions of about 50%, with the PSH group reporting a 25% reduction. Women receiving the PSH reported statistically significantly smaller reductions in hot flash score than women in the referent VSH arm (P = 0.001). There were no significant negative side effects during the course of the study. CONCLUSIONS: Hypnosis alone reduced hot flashes equal to venlafaxine alone, but the combination of hypnosis and venlafaxine did not reduce hot flashes more than either treatment alone. More research is needed to clarify whether combining hypnosis with a different antidepressant would provide synergistic benefits.

The Effect of a Youth-Centered Sexual Risk Event History Calendar (SREHC) Assessment on Sexual Risk Attitudes, Intentions, and Behavior.

INTRODUCTION: The purpose of this study was to examine the effect of a youth-centered assessment, the Sexual Risk Event History Calendar (SREHC), compared with the Guidelines for Adolescent Preventive Services (GAPS) assessment, on sexual risk attitudes, intentions, and behaviors. METHODS: The Interaction Model of Client Health Behavior guided this participatory research-based randomized control trial. Youth participants recruited from university and community clinics in the Midwestern United States were randomized to a health care provider visit using either the SREHC or GAPS and completed surveys at baseline, postintervention, and 3, 6, and 12 months. RESULTS: Participants included 181 youth (15-25 years old) and nine providers. Findings showed that youth in the SREHC group reported stronger intentions to use condoms compared with those in the GAPS group. Age and race were also significant predictors of sexual experience. DISCUSSION: This study highlights the importance of using a youth-centered, systematic approach in the assessment of sexual risk behaviors.

Gender differences in use of hearing protection devices among farm operators.

PURPOSE: Although farm operators have frequent exposure to hazardous noise and high rates of noise-induced hearing loss, they have low use of hearing protection devices (HPDs). Women represent about one-third of farm operators, and their numbers are climbing. However, among published studies examining use of HPDs in this worker group, none have examined gender-related differences. The purpose of this study was to examine gender-related differences in use of hearing protection and related predictors among farm operators. MATERIALS AND METHODS: Data previously collected at farm shows and by telephone were analyzed using t-tests and generalized linear model with zero inflated negative binomial (ZINB) distribution. FINDINGS: The difference in rate of hearing protector use between men and women farm operators was not significant. There was no difference between men and women in most hearing protector-related attitudes and beliefs. CONCLUSION: Although men and women farm operators had similar rates of use of hearing protectors when working in high-noise environments, attitudes about HPD use differed. Specifically, interpersonal role modeling was a predictor of HPD use among women, but not for men. This difference suggests that while farm operators of both genders may benefit from interventions designed to reduce barriers to HPD use (e.g., difficulty communicating with co-workers and hearing warning sounds), farm women have unique needs in relation to cognitive-perceptual factors that predict HPD use. Women farm operators may lack role models for use of HPDs (e.g., in peers and advertising), contributing to their less frequent use of protection.

Developing a Hypnotic Relaxation Intervention to Improve Body Image: A Feasibility Study.

PURPOSE/OBJECTIVES: To determine the content, feasibility, and best outcome of a mind-body intervention involving self-directed hypnotic relaxation to target body image.
. DESIGN: A five-week, uncontrolled, unblinded feasibility intervention study.
. SETTING: Behavioral therapy offices in Ann Arbor, Michigan, and Waco, Texas.
. SAMPLE: 10 female breast cancer survivors and 1 breast and gynecologic cancer survivor. 
. METHODS: Adult women with a history of breast and gynecologic cancer and no major psychiatric history were eligible. The intervention included four face-to-face sessions with a research therapist lasting 40-60 minutes, logged home practice, one telephone check-in call at week 5, and one intervention feedback telephone call to complete the study. Descriptive statistics and paired t-tests were used to test feasibility and content validity.
. MAIN RESEARCH VARIABLES: Stress from body changes as measured by the Impact of Treatment Scale, sexual function as measured by the Female Sexual Function Index, and sexual self-image as measured by the Sexual Self-Schema Scale for women were the variables of interest.
. FINDINGS: The intervention content was confirmed. Changes in scores from the baseline to week 5 suggested that stress from body changes decreased and sexual self-schema and function improved during the intervention. Nine of the 11 women were satisfied with the intervention, and all 11 indicated that their body image improved. 
. CONCLUSIONS: Hypnotic relaxation therapy shows promise for improving body image and, in doing so, improving sexual health in this population. Additional testing of this intervention is warranted.
. IMPLICATIONS FOR NURSING: Hypnotic relaxation therapy is feasible to improve body image and sexual health in women diagnosed with cancer and may be an important intervention that could be offered by nurses and other behavioral therapists.

Who's not driving among U.S. high school seniors: A closer look at race/ethnicity, socioeconomic factors, and driving status.

OBJECTIVES: We examined associations among race/ethnicity, socioeconomic factors, and driving status in a nationally representative sample of >26,000 U.S. high school seniors. METHODS: Weighted data from the 2012 and 2013 Monitoring the Future surveys were combined and analyzed. We imputed missing values using fully conditional specification multiple imputation methods. Multivariate logistic regression modeling was conducted to explore associations among race/ethnicity, socioeconomic factors, and driving status, while accounting for selected student behaviors and location. Lastly, odds ratios were converted to prevalence ratios. RESULTS: 23% of high school seniors did not drive during an average week; 14% of white students were nondrivers compared to 40% of black students. Multivariate analysis revealed that minority students were 1.8 to 2.5 times more likely to be nondrivers than their white counterparts, and students who had no earned income were 2.8 times more likely to be nondrivers than those earning an average of ≥$36 a week. Driving status also varied considerably by student academic performance, number of parents in the household, parental education, census region, and urbanicity. CONCLUSIONS: Our findings suggest that resources-both financial and time-influence when or whether a teen will learn to drive. Many young people from minority or lower socioeconomic families who learn to drive may be doing so after their 18th birthday and therefore would not take advantage of the safety benefits provided by graduated driver licensing. Innovative approaches may be needed to improve safety for these young novice drivers.

Effects of interventions on use of hearing protectors among farm operators: A randomized controlled trial.

OBJECTIVE: The purpose of this study was to compare the effectiveness of three interventions designed to promote hearing protector device (HPD) use. DESIGN: Randomized controlled trial. STUDY SAMPLE: Farm operators (n = 491) were randomly assigned to one of five intervention groups: (1) interactive web-based information with mailed assortment of HPDs; (2) Interactive web-based information only; (3) static web-based information with mailed assortment of HPDs; (4) Static web-based information only; or (5) mailed assortment of HPDs only. Data were analysed using a mixed model approach. RESULTS: HPD use increased among all participants, and increased more among participants receiving the mailed HPDs (with or without information) compared to participants receiving other interventions. Participants receiving the interactive web-based information had comparable increased use of HPDs to those receiving the static web-based information. Participants receiving the mailed HPDs had more positive situational influences scale scores than other participants. Program satisfaction was highest among mailed and web-based information groups. CONCLUSIONS: A mailed assortment of hearing protectors was more effective than information. Interactive and static information delivered via web were similarly effective. Programs interested in increasing HPD use among farmers should consider making hearing protectors more available to farmers.

Protocol of a test of hearing health education programs for farm and rural youth.

BACKGROUND: Farm and rural youth have frequent exposure to hazardous noise on the farm and recreationally, and have an increased prevalence of noise-induced hearing loss. There is a lack of programs to prepare this high-risk population to use hearing conservation strategies. METHODS: The purpose of this project is to test innovative hearing health education programs delivered to a large target group and to determine the effectiveness and sustainability of these programs in promoting hearing health among farm and rural youth. Specifically, this project includes: a) an interactive face-to-face informational program alone, b) an interactive face-to-face informational program followed by an Internet-based booster, and c) a no-intervention control. Sites will include selected affiliates of a major farm youth safety education organization. Data will be collected at baseline, 3, and 12 months. A linear mixed model will be used to compare the effectiveness of the three interventions over time. Descriptive statistics will be used to compare program costs and sustainability ratings. DISCUSSION: Outcomes of this project will provide knowledge necessary to implement quality and cost-effective services to farm and rural youth, a high-risk and underserved population, that can be implemented and sustained after the study is completed. TRIAL REGISTRATION: Clinicaltrials.gov NCT02472821 Registered 09 Jun, 2015.

Alcohol-Impaired Driving Among Adults - United States, 2012.

Alcohol-impaired driving crashes account for approximately one third of all crash fatalities in the United States. In 2013, 10,076 persons died in crashes in which at least one driver had a blood alcohol concentration (BAC) ≥0.08 grams per deciliter (g/dL), the legal limit for adult drivers in the United States. To estimate the prevalence, number of episodes, and annual rate of alcohol-impaired driving, CDC analyzed self-reported data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. An estimated 4.2 million adults reported at least one alcohol-impaired driving episode in the preceding 30 days, resulting in an estimated 121 million episodes and a national rate of 505 episodes per 1,000 population annually. Alcohol-impaired driving rates varied by more than fourfold among states, and were highest in the Midwest U.S. Census region. Men accounted for 80% of episodes, with young men aged 21-34 years accounting for 32% of all episodes. Additionally, 85% of alcohol-impaired driving episodes were reported by persons who also reported binge drinking, and the 4% of the adult population who reported binge drinking at least four times per month accounted for 61% of all alcohol-impaired driving episodes. Effective strategies to reduce alcohol-impaired driving include publicized sobriety checkpoints, enforcement of 0.08 g/dL BAC laws, requiring alcohol ignition interlocks for everyone convicted of driving while intoxicated, and increasing alcohol taxes.

Proteomic analysis of human plasma in chronic rheumatic mitral stenosis reveals proteins involved in the complement and coagulation cascade.

BACKGROUND: Rheumatic fever in childhood is the most common cause of Mitral Stenosis in developing countries. The disease is characterized by damaged and deformed mitral valves predisposing them to scarring and narrowing (stenosis) that results in left atrial hypertrophy followed by heart failure. Presently, echocardiography is the main imaging technique used to diagnose Mitral Stenosis. Despite the high prevalence and increased morbidity, no biochemical indicators are available for prediction, diagnosis and management of the disease. Adopting a proteomic approach to study Rheumatic Mitral Stenosis may therefore throw some light in this direction. In our study, we undertook plasma proteomics of human subjects suffering from Rheumatic Mitral Stenosis (n = 6) and Control subjects (n = 6). Six plasma samples, three each from the control and patient groups were pooled and subjected to low abundance protein enrichment. Pooled plasma samples (crude and equalized) were then subjected to in-solution trypsin digestion separately. Digests were analyzed using nano LC-MS(E). Data was acquired with the Protein Lynx Global Server v2.5.2 software and searches made against reviewed Homo sapiens database (UniProtKB) for protein identification. Label-free protein quantification was performed in crude plasma only. RESULTS: A total of 130 proteins spanning 9-192 kDa were identified. Of these 83 proteins were common to both groups and 34 were differentially regulated. Functional annotation of overlapping and differential proteins revealed that more than 50% proteins are involved in inflammation and immune response. This was corroborated by findings from pathway analysis and histopathological studies on excised tissue sections of stenotic mitral valves. Verification of selected protein candidates by immunotechniques in crude plasma corroborated our findings from label-free protein quantification. CONCLUSIONS: We propose that this protein profile of blood plasma, or any of the individual proteins, could serve as a focal point for future mechanistic studies on Mitral Stenosis. In addition, some of the proteins associated with this disorder may be candidate biomarkers for disease diagnosis and prognosis. Our findings might help to enrich existing knowledge on the molecular mechanisms involved in Mitral Stenosis and improve the current diagnostic tools in the long run.

Clinical significance of markers of collagen metabolism in rheumatic mitral valve disease.

BACKGROUND: Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. METHODOLOGY: This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant. RESULTS: Plasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = -0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = -0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = -0.48 respectively) and systolic diameters (r = 0.65; r = -0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91-0.99; p<0.0001). A cut-off >459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. CONCLUSIONS: Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis.