Zinc supplementation reduced DNA breaks in Ethiopian women.

Assessment of zinc status remains a challenge largely because serum/plasma zinc may not accurately reflect an individual's zinc status. The comet assay, a sensitive method capable of detecting intracellular DNA strand breaks, may serve as a functional biomarker of zinc status. We hypothesized that effects of zinc supplementation on intracellular DNA damage could be assessed from samples collected in field studies in Ethiopia using the comet assay. Forty women, from villages where reported consumption of meat was less than once per month and phytate levels were high, received 20 mg zinc as zinc sulfate or placebo daily for 17 days in a randomized placebo-controlled trial. Plasma zinc concentrations were determined by inductively coupled plasma mass spectrometry. Cells from whole blood at the baseline and end point of the study were embedded in agarose, electrophoresed, and stained before being scored by an investigator blinded to the treatments. Although zinc supplementation did not significantly affect plasma zinc, mean (± SEM) comet tail moment measurement of supplemented women decreased from 39.7 ± 2.7 to 30.0 ± 1.8 (P< .005), indicating a decrease in DNA strand breaks in zinc-supplemented individuals. These findings demonstrated that the comet assay could be used as a functional assay to assess the effects of zinc supplementation on DNA integrity in samples collected in a field setting where food sources of bioavailable zinc are limited. Furthermore, the comet assay was sufficiently sensitive to detect changes in zinc status as a result of supplementation despite no significant changes in plasma zinc.

Alfaxalone-butorphanol versus alfaxalone-morphine combination for immersion anaesthesia in oriental fire-bellied toads (Bombina orientalis)

Oriental fire-bellied toads (Bombina orientalis) are small semi-aquatic anuran species popular as both pets and laboratory animals. Although they are commonly anaesthetized to undergo clinical and experimental procedures, very little is known about their anaesthetic management. The aims of this prospective, randomized, cross-over experimental trial were to establish effective butorphanol and morphine concentrations to be added to alfaxalone for immersion anaesthesia (pilot study), and to compare the anaesthetic and antinociceptive effects of the two drug mixtures (alfaxalone-butorphanol and alfaxalone-morphine), in Bombina orientalis toads. For the actual trial, the toads were randomly assigned to one of two treatment groups: AB and AM, with seven animals in each group, which received alfaxalone-butorphanol and alfaxalone-morphine combinations, respectively, at the concentrations established during the pilot study. Heart rate, respiratory rate, von Frey filament threshold and response to nociceptive withdrawal (NWR), righting and myotactic reflexes were measured at 5 min intervals until return of righting reflex was observed. The investigator who carried out all the measurements was blinded to the treatment. Any undesired effect or complication was noted and recorded. The two treatments were found to be comparable in terms of onset and duration of anaesthesia, and occurrence of undesired effects. However, group AM resulted in lower NWR scores and higher von Frey filament thresholds than group AB. It is concluded that, at the investigated concentrations and in combination with alfaxalone by immersion, morphine provides better antinociception than butorphanol in oriental fire-bellied toads.

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction.

AIMS Our aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial. METHODS AND RESULTS The BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis. CONCLUSIONS In this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Retrievability of implant-supported crowns when using three different cements: a controlled clinical trial

PURPOSE The purpose of this study was to analyze the removal of implant-supported crowns retained by three different cements using an air-accelerated crown remover and to evaluate the patients' response to the procedure. MATERIALS AND METHODS This controlled clinical trial was conducted with 21 patients (10 women, 11 men; mean age: 51 ± 10.2 years) who had received a total of 74 implants (all placed in the posterior zone of the mandible). Four months after implant surgery, the crowns were cemented on standard titanium abutments of different heights. Three different cements (two temporary: Harvard TEMP and Improv; and one definitive: Durelon) were used and randomly assigned to the patients. Eight months later, one blinded investigator removed all crowns. The number of activations of the instrument (CORONAflex, KaVo) required for crown removal was recorded. The patients completed a questionnaire retrospectively to determine the impact of the procedure and to gauge their subjective perception. A linear regression model and descriptive statistics were used for data analysis. RESULTS All crowns could be retrieved without any technical complications or damage. Both abutment height (P = .019) and cement type (P = .004) had a significant effect on the number of activations, but the type of cement was more important. An increased total number of activations had no or only a weak correlation to the patients' perception of concussion, noise, pain, and unwillingness to use the device. CONCLUSIONS Cemented implant crowns can be removed, and the application of an air-accelerated device is a practicable method. A type of cement with appropriate retention force has to be selected. The impact on the patients' subjective perception should be taken into account.

Involuntary reflexive pelvic floor muscle training in addition to standard training versus standard training alone for women with stress urinary incontinence: study protocol for a randomized controlled trial

BACKGROUND Pelvic floor muscle training is effective and recommended as first-line therapy for female patients with stress urinary incontinence. However, standard pelvic floor physiotherapy concentrates on voluntary contractions even though the situations provoking stress urinary incontinence (for example, sneezing, coughing, running) require involuntary fast reflexive pelvic floor muscle contractions. Training procedures for involuntary reflexive muscle contractions are widely implemented in rehabilitation and sports but not yet in pelvic floor rehabilitation. Therefore, the research group developed a training protocol including standard physiotherapy and in addition focused on involuntary reflexive pelvic floor muscle contractions. METHODS/DESIGN The aim of the planned study is to compare this newly developed physiotherapy program (experimental group) and the standard physiotherapy program (control group) regarding their effect on stress urinary incontinence. The working hypothesis is that the experimental group focusing on involuntary reflexive muscle contractions will have a higher improvement of continence measured by the International Consultation on Incontinence Modular Questionnaire Urinary Incontinence (short form), and - regarding secondary and tertiary outcomes - higher pelvic floor muscle activity during stress urinary incontinence provoking activities, better pad-test results, higher quality of life scores (International Consultation on Incontinence Modular Questionnaire) and higher intravaginal muscle strength (digitally tested) from before to after the intervention phase. This study is designed as a prospective, triple-blinded (participant, investigator, outcome assessor), randomized controlled trial with two physiotherapy intervention groups with a 6-month follow-up including 48 stress urinary incontinent women per group. For both groups the intervention will last 16 weeks and will include 9 personal physiotherapy consultations and 78 short home training sessions (weeks 1-5 3x/week, 3x/day; weeks 6-16 3x/week, 1x/day). Thereafter both groups will continue with home training sessions (3x/week, 1x/day) until the 6-month follow-up. To compare the primary outcome, International Consultation on Incontinence Modular Questionnaire (short form) between and within the two groups at ten time points (before intervention, physiotherapy sessions 2-9, after intervention) ANOVA models for longitudinal data will be applied. DISCUSSION This study closes a gap, as involuntary reflexive pelvic floor muscle training has not yet been included in stress urinary incontinence physiotherapy, and if shown successful could be implemented in clinical practice immediately. TRIAL REGISTRATION NCT02318251 ; 4 December 2014 First patient randomized: 11 March 2015.

Assessment of readiness to initiate antiretroviral therapy

An important factor in determining a patient's adherence to antiretroviral therapy is the patient's commitment to follow the regimen. This suggests that therapy should be initiated when the patient is willing to commit to the regimen. Starting when the patient is ready may be more important than the laboratory values suggested by various guidelines. In order to increase understanding of patient readiness for antiretroviral therapy HIV infected patients were surveyed to determine the factors that influenced their decision to initiate antiretroviral therapy and to continue to adhere to therapy once started. A sample of 83 HIV infected patients who were currently on antiretroviral regimens completed a 25-item investigator-developed questionnaire. The questionnaire sought information on the length of time from learning of HIV positive status and readiness to initiate therapy. The questionnaire also addressed demographic, psychological and social factors thought to be associated with readiness for adhering to therapy. (Abstract shortened by UMI.)^

The role of the experience and expression of anger in future cardiovascular profiles in young adolescents

Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

Psychiatrists' and Psychiatric APRNs' Views of the Adolescent Mental Health Nurse's Role In the Inpatient Setting

Current perceptions about nurses’ roles and responsibilities are examined in this study, specifically relating to adolescent inpatient MHNs. Psychiatrists and psychiatric advanced practice registered nurses (APRNs), who work with MHNs and have also published scholarly psychiatric articles, were contacted to request their participation in an anonymous survey hosted by SurveyMonkey.com. This research was conducted to examine the stereotypes that exist against nurses within the health care profession itself, as compared to the pre-existing stereotypes displayed by the media’s view of nurses. Due to investigator time constraints, only six subjects participated in the study. Analysis of survey responses revealed four overarching themes. First, MHNs are a critical component of the health care team, emerging as rigorous, independent leaders, although still classified as female and sociable. Second, MHNs complete a wide range of daily activities, many of which go unnoticed by observers, often resulting in mixed feelings regarding whether MHNs are given the respect and recognition deserved. Third, MHNs treat each patient as a person with unique thoughts, feelings, and physical make-up. Fourth, MHNs act as a coordinator of care between various health professionals to provide the patient with a holistic approach to healing.

Using GIS methods to assess the occurrence of neural tube defect births by residential proximity at conception to hazardous waste sites

In the United States, approximately 4,000 pregnancies each year are affected by the two most common birth defects, spina bifida and anencephaly. Studies have shown that exposure to environmental chemicals before and after conception may adversely affect reproduction by inducing cell death or dysfunction, which leads to infertility, fetal loss, lowered weight at birth, or birth anomalies in the offspring. The objective of the study was to evaluate the relationship between Neural Tube Defect births and residence at conception in proximity to hazardous waste sites in the Texas-Mexico border region between 1993 and 2000. ^ The study design was a nested matched case-control and utilized secondary data from a project, “The role of chemical and biological factors in the etiology of neural tube birth defects births along the Texas-Mexico Border” (Irina Cech, Principal Investigator). Geographic Information Systems (GIS) database methods were used to compare Neural Tube Defects cases to controls on status of conception residence occurring within a one-mile radius from hazardous waste sites, as compared to conception residence further away. Information on the exposures was obtained from the OnTarget Database and Environment Protection Agency website. Conditional logistic regression was used for the matched case-control study to investigate the relationship between an outcome of being a case or a control and proximity to hazardous waste sites. ^ The result of the study showed a 36 percent non-significant increased risk of having an NTD birth associated with maternal proximity to abandoned hazardous waste sites (95% CI = 0.62–3.02). In addition, there was a 24% non-significant elevated risk of having an NTD birth when living in proximity to air pollutant sites than when living further away (95% CI = 0.67–2.32). Although this study did not find statistically significant associations, it will expand on the existing knowledge of the relationship between NTD and proximity to hazardous waste sites. ^

Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

Trends in anti-tuberculosis drug resistance from 2003--2007 at Pham Ngoc Thach tuberculosis and lung disease hospital, Ho Chi Minh City, Vietnam

Vietnam is one of the countries with the highest prevalence and incidence of tuberculosis (TB) in the world (1). Although Vietnam has had many successes in TB control, it still faces the challenge of drug resistant and multidrug-resistant tuberculosis (MDR-TB). MDR-TB appears to be relatively stable, but data on MDR-TB continues to be scarce and routine testing of all isolates for drug susceptibility is not performed under Vietnam's National Tuberculosis Program (6). Pham Ngoc Thach Hospital (PNT), the leading tuberculosis and lung disease hospital in Ho Chi Minh City, serves as a reference hospital and laboratory for both Ho Chi Minh City and the Southern Vietnam region. This study is an unmatched, nested case-control study consisting of a secondary analysis of a previously created dataset composed of drug susceptibility and basic demographic data from a cohort of patients diagnosed with tuberculosis at PNT from 2003 through 2007 in order to calculate the prevalence of resistance among acid-fast bacilli smear-positive patients. The susceptibility records for the years 2003-2004 were not representative of the entire population, but over the years 2005-2007 the investigator found a decrease in resistance to all primary TB drugs on which records were available, as well as MDR-TB. Overall, females showed a higher proportion of resistance to TB drugs than males, and females had a greater likelihood of presenting with MDR-TB than males (OR=1.77). Persons 35-54 had greater likelihood of having MDR-TB than younger and older age groups. Among the population with HIV data, HIV-positivity was associated with greater likelihood of MDR-TB (OR=1.70, 95% CI=0.97-3.11). This study shows that rates of TB drug resistance are high, but declining, in one of Vietnam's largest TB hospitals, and that females and HIV-positive individuals are possible high-risk groups in this population.^

Qualitative study: Understanding Mexican American women's experience in intimate partner violence

The purpose of this qualitative study was to gain an understanding of the experiences of Mexican American women living with intimate partner abuse relevant to the process of disclosure of abuse. Limited research exists on the experiences of women who are of Mexican descent living with intimate partner abuse and their disclosure of abuse. Factors that influence disclosure for other populations are well articulated in the literature however, these factors have not been adequately verified in persons of Mexican descent. Data are reported from in-depth interviews with 26 clients at a shelter and an outreach agency in a south Texas-Mexico border community. Semi-structured interview guide was used to elicit information over an 11 month period. A grounded theory ethnography approach was used to analyze data. Verification strategies and constant comparison techniques (e.g. investigator responsiveness, methodological coherence, sampling adequacy, an active analytic stance, and saturation) enhanced rigor of analysis. Nineteen Mexican immigrant women and seven Mexican American women participated in the study. Several themes were discerned related to women's experiences in abuse: painful living, questioning endurance, and confronting reality. In almost every participant's account there was a description of repeated victimization by her intimate partner or partners, and again, by others within and outside her network. The participants discussed several cultural factors (e.g. embarrassment, concerns for family, avoidance of causing pain to family, protection of partner, avoidance of being judged) that hindered their decisions whether or not to disclose. Participants noted that healthcare workers rarely asked probing questions regarding abuse. The timing and process of disclosure took many turns for women in this study. Some of the factors hindering women from disclosing were found to be influenced by cultural practices. The consequences of disclosure for many of the women led them to re-victimization. Implications for practice to avoid missed opportunities with women living in abuse are to: ask questions routinely to encourage disclosure of abuse and offer community resource information for women living in abuse or both.^

Mean corpuscular volume as a marker for adherence to antiretroviral therapy among HIV infected children and adolescents in Uganda

Mean corpuscular volume, which is an inexpensive and widely available measure to assess, increases in HIV infected individuals receiving zidovudine and stavudine raising the hypothesis that it could be used as a surrogate for adherence.^ The aim of this study was to examine the association between mean corpuscular volume and adherence to antiretroviral therapy among HIV infected children and adolescents aged 0–19 years in Uganda as well as the extent to which changes in mean corpuscular volume predict adherence as determined by virologic suppression.^ The investigator retrospectively reviewed and analyzed secondary data of 158 HIV infected children and adolescents aged 0–19 years who initiated antiretroviral therapy under an observational cohort at the Baylor College of Medicine Children's Foundation - Uganda. Viral suppression was used as the gold standard for monitoring adherence and defined as viral load of < 400 copies/ml at 24 and 48 weeks. ^ Patients were at least 48 weeks on therapy, age 0.2–18.4 years, 54.4% female, 82.3% on zidovudine based regimen, 92% WHO stage III at initiation of therapy, median pre therapy MCV 80.6 fl (70.3–98.3 fl), median CD4% 10.2% (0.3%–28.0%), and mean pre therapy viral load 407,712.9 ± 270,413.9 copies/ml. For both 24 and 48 weeks of antiretroviral therapy, patients with viral suppression had a greater mean percentage change in mean corpuscular volume (15.1% ± 8.4 vs. 11.1% ± 7.8 and 2.3% ± 13.2 vs. -2.7% ± 10.5 respectively). The mean percentage change in mean corpuscular volume was greater in the first 24 weeks of therapy for patients with and without viral suppression (15.1% ± 8.4 vs. 2.3% ± 13.2 and 11.1% ± 7.8 vs. -2.7% ± 10.5 respectively). In the multivariate logistic regression model, percentage change in mean corpuscular volume ≥ 20% was significantly associated with viral suppression (adjusted OR 4.0; CI 1.2–13.3; p value 0.02). The ability of percentage changes in MCV to correctly identify children and adolescents with viral suppression was higher at a cut off of ≥ 20% (90.7%; sensitivity, 31.7%) than at ≥ 9% (82.9%; sensitivity, 78.9%). Negative predictive value was lower at ≥ 20% change (25%; specificity, 84.8%) than at ≥ 9% change (33.3%; specificity, 39.4%).^ Mean corpuscular volume is a useful marker of adherence among children and adolescents with viral suppression. ^