RELATION OF TYPE OF REPORTED ILLNESSES TO PATTERN OF USE OF THE STUDENT HEALTH CENTER BY THE INTERNATIONAL STUDENTS AT TEXAS SOUTHERN UNIVERSITY, HOUSTON, TEXAS

The state of knowledge on the relation of stress factors, health problems and health service utilization among university students is limited. Special problems of stress exist for the international students due to their having to adjust to a new environment. It is this latter problem area that provides the focus for this study. Recognizing there are special stress factors affecting the international students, it is first necessary to see if the problems of cultural adaptation affect them to any greater degree than American students attending the same university.^ To make the comparison, the study identified a number of health problems of both American and international students and related their frequency to the use of the Student Health Center. The expectation was that there would be an association between the number of health problems and the number of life change events experienced by these students and between the number of health problems and stresses from social factors. It was also expected that the number of health problems would decline with the amount of social support.^ The population chosen were students newly enrolled in Texas Southern University, Houston, Texas in the Fall Semester of 1979. Two groups were selected at random: 126 international and 126 American students. The survey instrument was a self-administered questionnaire. The response rate was 90% (114) for the international and 94% (118) for the American students.^ Data analyses consisted of both descriptive and inferential statistics. Chi-squares and correlation coefficients were the statistics used in comparing the international students and the American students.^ There was a weak association between the number of health problems and the number of life change events, as reported by both the international and the American students. The study failed to show any statistically significant association between the number of stress from social factors and the number of health problems. It also failed to show an association between the number of health problems and the amount of social support. These findings applied to both the international and the American students.^ One unexpected finding was that certain health problems were reported by more American than international students. There were: cough, diarrhea, and trouble in sleeping. Another finding was that those students with health insurance had a higher level of utilization of the Health Center than those without health insurance. More international than American students utilized the Student Health Center.^ In comparing the women students, there was no statistical significant difference in their reported fertility related health problems.^ The investigator recommends that in follow-up studies, instead of grouping all international students together, that they be divided by major nationalities represented in the student body; that is, Iranians, Nigerians and others. ^

THE RELATIONSHIP OF PRESCRIPTION RECEIPT AND EXPECTATION OF SICK-ROLE LEGITIMATION BY AMBULATORY VETERANS

This study explored the relationship of attitudes, needs, and health services utilization patterns of elderly veterans who were identified and categorized by their expectation for and receipt of sick-role legitimation. Three prescription types (new, change, renewal) were defined as the operational variables. A population of 676 ambulatory, chronically ill (average age 60 years) veterans were sent a questionnaire (74% response rate). In addition, retrospective medical and prescription record review was performed for a 45% sample of respondents. The results were analyzed using discriminant function and regression analysis. Fewer than 20% of the veterans responding expected to receive more prescriptions than were presently prescribed, whereas over 80% expected refill authorizations. Distinct attitudinal, need, and utilization patterns were identified. ^

A feasibility study for assessing building occupants' indoor air quality expectations compared to nationally recognized standards

Indoor Air Quality (IAQ) can have significant implications for health, productivity, job performance, and operating cost. Professional experience in the field of indoor air quality suggests that high expectations (better than nationally established standards) (American Society of Heating, Refrigerating, and Air-conditioning Engineers (ASHRAE)) of workplace indoor air quality lead to increase air quality complaints. To determine whether there is a positive association between expectations and indoor air quality complaints, a one-time descriptive and analytical cross-sectional pilot study was conducted. Area Safety Liaisons (n = 330) at University of Texas Health Science Center – Houston were asked to answer a questionnaire regarding their expectations of four workplace indoor air quality indicators i.e., (temperature, relative humidity, carbon dioxide, and carbon monoxide) and if they experienced and reported indoor air quality problems. A chi-square test for independence was used to evaluate associations among the variables of interest. The response rate was 54% (n = 177). Results did not show significant associations between expectation and indoor air quality. However, a greater proportion of Area Safety Liaisons who expected indoor air quality indicators to be better than the established standard experienced greater indoor air quality problems. Similarly, a slightly higher proportion of Area Liaisons who expected indoor air quality indicators to be better than the standard reported greater indoor air quality complaints. ^ The findings indicated that a greater proportion of Area Safety Liaisons with high expectations (conditions that are beyond what is considered normal and acceptable by ASHRAE) experienced greater indoor air quality discomfort. This result suggests a positive association between high expectations and experienced and reported indoor air quality complaints. Future studies may be able to address whether the frequency of complaints and resulting investigations can be reduced through information and education about what are acceptable conditions.^

Relationship between nurse leader emotional intelligence and registered nurse job satisfaction

Aim: To determine the relationship between nurse leader emotional intelligence and registered nurse job satisfaction. ^ Background: Nurse leaders influence the work environments of nurses working at the bedside. Nursing leadership plays an important role in fostering work environments that attract and retain nurses. ^ Methods: A non-experimental, predictive design study conducted in 5 hospitals evaluated relationships between 31 nurse leaders and 799 registered nurses. The nurse leaders were administered the MSCEIT and MBTI. The registered nurses participated in the 2010 NDNQI RN Job Satisfaction Survey. ^ Measurements and Results: The sample population completed two online instruments, the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Myers Brigg Trait Inventory (MBTI). Nurse leader demographic data was collected consisting of age, sex, race, educational level, certification status and years in the profession of nursing. The relationships among characteristics of the nurse leader and staff nurses were examined using regression analysis and stepwise deletion. The results from the MBTI were obtained electronically from CPP. Inc. and the results of MSCEIT were obtained electronically from MHS, Inc. The nurse leader response rate was 46% and the NDNQI RN Job Satisfaction response rate was 62%. The sample of 31 nurse leaders were 65 percent female and 67.7% were White, 12.9% Black, and 19.4% Hispanic. The most prevalent MBTI type was ESTJ (19.35%), followed by ENFJ and ISFJ (9.68% each). The nurse leader sample was primarily extroverts (n=20), sensing (n=18), thinking (n=16) and judging (n=19). The nurse leaders' overall MSCEIT scores ranged from 69 to 111 (implying a range from those who should consider development to competent) with a mean score of 89.84 (consider improvement). The nurse leaders scored highest in the MSCEIT Facilitating subscale with scores ranging from 69 to 121 (consider development to strength) and a mean score of 95.19 (low average score). The overall mean MSCEIT mean scores for the entire sample ranged from 89.90 to 95.19 (consider emotional intelligence improvement to low average score) Overall, staff nurse participants in the NDNQI RN Job Satisfaction Survey were moderately satisfied with the nurse leaders as noted by a mean t score of 55.03 of 60 and this score was consistent with the comparison hospitals that participated in the 2010 NDNQI RN Job Satisfaction Survey (American Nurses Association, 2010). Staff nurses gave nurse leaders a mean score of 4.50 for patient assignments appropriate, and rated a mean score of 4.35 and moderately agreeing to recommend the hospital to a friend. ^ Conclusions: Future research is needed to determine if there is a relationship between nurse leader emotional intelligence ability and registered nurse job satisfaction. Additional research is also needed to determine what to measure in regards to nurse leader emotional intelligence, ability or behavior. Another issue that emerged in the examination of EI is the moderating relationship between the nurse leaders span of control and staff nurse satisfaction on the NDNQI. ^

Bayesian Adaptive Designs for Early Phase Clinical Trials

My dissertation focuses mainly on Bayesian adaptive designs for phase I and phase II clinical trials. It includes three specific topics: (1) proposing a novel two-dimensional dose-finding algorithm for biological agents, (2) developing Bayesian adaptive screening designs to provide more efficient and ethical clinical trials, and (3) incorporating missing late-onset responses to make an early stopping decision. Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which toxicity and efficacy monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a phase I/II trial design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multi-arm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while at the same time allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while at the same time providing higher power to identify the best treatment at the end of the trial. Phase II trial studies usually are single-arm trials which are conducted to test the efficacy of experimental agents and decide whether agents are promising to be sent to phase III trials. Interim monitoring is employed to stop the trial early for futility to avoid assigning unacceptable number of patients to inferior treatments. We propose a Bayesian single-arm phase II design with continuous monitoring for estimating the response rate of the experimental drug. To address the issue of late-onset responses, we use a piece-wise exponential model to estimate the hazard function of time to response data and handle the missing responses using the multiple imputation approach. We evaluate the operating characteristics of the proposed method through extensive simulation studies. We show that the proposed method reduces the total length of the trial duration and yields desirable operating characteristics for different physician-specified lower bounds of response rate with different true response rates.

Long Term Follow-up of Morbidity and Quality of Life Associated with Isolated Gastroschisis

Gastroschisis is a birth defect in which an opening in the abdominal wall allows herniation of the viscera. Prenatal counseling regarding gastroschisis typically discusses that, although these infants often endure a difficult neonatal course, they experience few long-term complications. However, information regarding long-term outcomes is based on limited studies that lack specificity. Therefore, we aimed to study the long-term morbidity and quality of life in children born with gastroschisis in a large and diverse population drawn from the Texas Birth Defects Registry (TBDR). Study packets with informed consent, a questionnaire, and the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL 4.0) in English and Spanish were mailed to 1,112 parents of children born with isolated gastroschisis in Texas between 1999 and 2008 via the TBDR. Information was abstracted from the TBDR for 58 mothers of children with gastroschisis who returned study materials. Three hundred fifty five packets were returned to sender, giving a response rate of 7.7%. Children born with gastroschisis had quality of life scores that were not significantly different than expected (p = 0.981). However, factors such as having a learning disability (p = 0.001) and missing school due to gastrointestinal issues (p = 0.020) were found to significantly decrease quality of life. Overall, children with gastroschisis had a significantly increased risk for learning disabilities regardless of whether they were preterm (p = 0.021) or full term (p = 0.021). Additionally, there appeared to be an increased risk for auditory impairment in Caucasian children (p < 0.0005). Therefore, while overall long-term quality of life is not significantly altered for children born with gastroschisis, the previously unreported increased risk for learning disabilities and possible association with hearing impairment are important findings that should be conveyed to prospective parents.

A systematic review of personalized therapy in patients with advanced cancer

Background: An increased understanding of the pathogenesis of cancer at the molecular level has led to the development of personalized cancer therapy based on the mutation status of the tumor. Tailoring treatments to genetic signatures has improved treatment outcomes in patients with advanced cancer. We conducted a meta-analysis to provide a quantitative summary of the response to treatment on a phase I clinical trial matched to molecular aberration in patients with advanced solid tumors. ^ Methods: Original studies that reported the results of phase I clinical trials in patients with advanced cancer treated with matched anti-cancer therapies between January 2006 and November 2011 were identified through an extensive search of Medline, Embase, Web of Science and Cochrane Library databases. Odds Ratio (OR) with 95% confidence interval (CI) was estimated for each study to assess the strength of an association between objective response rate (ORR) and mutation status. Random effects model was used to estimate the pooled OR and their 95% CI was derived. Funnel plot was used to assess publication bias. ^ Results: Thirteen studies published between January 2006 and November 2011that reported on responses to matched phase I clinical trials in patients with advanced cancer were included in the meta-analysis. Nine studies reported on the responses seen in 538 of the 835 patients with driver mutations responsive to therapy and seven studies on the responses observed in 234 of the 306 patients with mutation predictive for negative response. Random effects model was used to estimate pooled OR, which was 7.767(95% CI = 4.199 − 14.366; p-value=0.000) in patients with activating mutations that were responsive to therapy and 0.287 (95% CI = 0.119 − 0.694; p-value=0.009) in patients with mutation predictive of negative response. ^ Conclusion: It is evident from the meta-analysis that somatic mutations present in tumor tissue of patients are predictive of responses to therapy in patients with advanced cancer in phase I setting. Plethora of research and growing evidence base indicate that selection of patients based on mutation analysis of the tumor and personalizing therapy is a step forward in the war against cancer.^

Retrospective assesment of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and early endometrioid endometrial cancer

Objective: The primary objective of this project was to describe the efficacy of the Levonorgestrel Intrauterine Device (LIUD) for treatment of Complex Endometrial Cancer (CAH) and Grade 1 Endometrial Cancer (G1EEC) in terms of rate of Complete Response (CR) and Partial Response (PR) after 6 months of therapy. Finally, we assessed if any clinical or pathologic features were associated with response to the LIUD. ^ Methods: This study was a retrospective case series designed to report the response rate of patients with CAH or G1EEC treated with LIUD therapy. In addition, this study has a laboratory component to assess molecular predictors of response to LIUD therapy. Retrospective data already collected from patients diagnosed with CAH or EEC grade 1 and treated with LIUD therapy at MD Anderson Cancer Center (MDACC) were used for this study. Patients from all ethnic and race groups were included. A Complete Response (CR) was defined in patients diagnosed with CAH if pathologic report at 6 months demonstrated either no evidence of hyperplasia or no atypia in the setting of simple or complex hyperplasia. Partial Response (PR) was recorded if disease downgraded to only CAH from G1EEC. No Response (NR) was recorded if pathologic report demonstrates no change (Stable Disease, SD) or progression to cancer (Progressive Disease, PD). We calculated the proportion of patients with complete response to LIUD therapy with 95% confidence interval. We compared the response rates (CR/PR vs NR) by obesity status (Obese if BMI > 40 kg/m2 vs non-obese if BMI <= 40 kg/m2) as well as other clinical and pathologic factors, such as age, uterine size (median size), and presence of exogenous progesterone effect. ^ Results: There were 39 patients diagnosed with either CAH or G1EEC treated with the LIUD. Of 39 patients, 12 did not have pathological results of biopsy at 6months time period. Of 27 evaluable patients, 17 were diagnosed with CAH and 10 with G1EEC. Overall response rate (RR) was 78% (95% CI = 62-94%) at 6 months, 18 patients had CR (4 in G1EEC; 14 in CAH), 3 patients had PR (3 in G1EEC), 3 had SD (1 in CAH; 2 in G1EEC), 3 had PD (2 in CAH; 1 in G1EEC). After histology stratification, RR at 6 months was 82.35% (14/17; 95%CI = 67.4-97.3%) in CAH and 70% (7/10; 95% CI = 41-98.4%) in G1EEC. ^ There was no difference in response (R) and no response (NR) based on BMI (p=0.56). He observed a trend showing association between age with response (p=0.1). There was no association between uterine size and response to therapy (p=0.17). We recorded strong association between exogenous progesterone effect and response. ^ Conclusion: LIUD therapy for the treatment of CAH and G1EEC may be effective and safe. Presence of exogenous progesterone effect may predict the response to LIUD therapy at earlier time points. There is need of further studies with larger sample size to explore the relationship of response with other clinical and pathologic factors^

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE Publication No.___________ Lisa Harn-Ging Shiue, B.S. Supervisory Professor: Madeleine Duvic, M.D. Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before and after ECP at Day 2, 1 month, 3 months, and 6 months. In this study, ECP was effective in 12/18 L-CTCL patients with a 66.7% overall response rate (ORR) and 6/11 GVHD patients with a 54.5% ORR. Prior to ECP, the percentages of CD4+Foxp3+ T cells in 9 L-CTCL patients were either lower (L-CTCL-Low, n=2) or higher (L-CTCL-High, n=7) than normal. Five of the 7 GVHD patients had high percentages of CD4+Foxp3+ T cells (GVHD-High). Six of 7 L-CTCL-High patients had >80% CD4+Foxp3+ T cells which were correlated with tumor cells, and were responders. Both L-CTCL-High and GVHD-High patients had decreased percentages of CD4+Foxp3+ and CD4+Foxp3+CD25- T cells after 3 months of treatment. CD4+Foxp3+CD25+ T cells increased in GVHD-High patients but decreased in L-CTCL-High patients after 3 months of ECP. In addition, numbers of CTLs were abnormal. We confirmed that numbers of CTLs were low in L-CTCL patients, but high in GVHD patients prior to ECP. After ECP, CTLs increased after 1 month in 4/6 L-CTCL patients whereas CTLs decreased after 6 months in 3/3 GVHD patients. Myeloid (mDCs) and plasmacytoid DCs (pDCs) were also low at baseline in L-CTCL and GVHD patients confirming the DC defect. After 6 months of ECP, numbers and percentages of mDCs and pDCs increased in L-CTCL and GVHD. MDCs were favorably increased in 8/12 L-CTCL responders whereas pDCs were favorably increased in GVHD patients. These data suggest that ECP is favorably modulating the DC subsets. In L-CTCL patients, the mDCs may orchestrate Th1 cell responses to overcome immune suppression and facilitate disease regression. However, in GVHD patients, ECP is favorably down-regulating the immune system and may be facilitating immune tolerance to auto-or allo-antigens. In both L-CTCL and GVHD patients, DCs are modulated, but the T cell responses orchestrated by the DCs are different, suggesting that ECP modulates depending on the immune milieu. _______________

Optimal, minimax, and Bayesian two-stage designs in two-dose phase II clinical trials

Background: For most cytotoxic and biologic anti-cancer agents, the response rate of the drug is commonly assumed to be non-decreasing with an increasing dose. However, an increasing dose does not always result in an appreciable increase in the response rate. This may especially be true at high doses for a biologic agent. Therefore, in a phase II trial the investigators may be interested in testing the anti-tumor activity of a drug at more than one (often two) doses, instead of only at the maximum tolerated dose (MTD). This way, when the lower dose appears equally effective, this dose can be recommended for further confirmatory testing in a phase III trial under potential long-term toxicity and cost considerations. A common approach to designing such a phase II trial has been to use an independent (e.g., Simon's two-stage) design at each dose ignoring the prior knowledge about the ordering of the response probabilities at the different doses. However, failure to account for this ordering constraint in estimating the response probabilities may result in an inefficient design. In this dissertation, we developed extensions of Simon's optimal and minimax two-stage designs, including both frequentist and Bayesian methods, for two doses that assume ordered response rates between doses. ^ Methods: Optimal and minimax two-stage designs are proposed for phase II clinical trials in settings where the true response rates at two dose levels are ordered. We borrow strength between doses using isotonic regression and control the joint and/or marginal error probabilities. Bayesian two-stage designs are also proposed under a stochastic ordering constraint. ^ Results: Compared to Simon's designs, when controlling the power and type I error at the same levels, the proposed frequentist and Bayesian designs reduce the maximum and expected sample sizes. Most of the proposed designs also increase the probability of early termination when the true response rates are poor. ^ Conclusion: Proposed frequentist and Bayesian designs are superior to Simon's designs in terms of operating characteristics (expected sample size and probability of early termination, when the response rates are poor) Thus, the proposed designs lead to more cost-efficient and ethical trials, and may consequently improve and expedite the drug discovery process. The proposed designs may be extended to designs of multiple group trials and drug combination trials.^

Study on the effect of metformin in patients of metastatic renal cell cancer with diabetes receiving tyrosine kinase inhibitor therapy

Objective: The primary objective of our study was to study the effect of metformin in patients of metastatic renal cell cancer (mRCC) and diabetes who are on treatment with frontline therapy of tyrosine kinase inhibitors. The effect of therapy was described in terms of overall survival and progression free survival. Comparisons were made between group of patients receiving metformin versus group of patients receiving insulin in diabetic patients of metastatic renal cancer on frontline therapy. Exploratory analyses were also done comparing non-diabetic patients of metastatic renal cell cancer receiving frontline therapy compared to diabetic patients of metastatic renal cell cancer receiving metformin therapy. ^ Methods: The study design is a retrospective case series to elaborate the response rate of frontline therapy in combination with metformin for mRCC patients with type 2 diabetes mellitus. The cohort was selected from a database, which was generated for assessing the effect of tyrosine kinase inhibitor therapy associated hypertension in metastatic renal cell cancer at MD Anderson Cancer Center. Patients who had been started on frontline therapy for metastatic renal cell carcinoma from all ethnic and racial backgrounds were selected for the study. The exclusion criteria would be of patients who took frontline therapy for less than 3 months or were lost to follow-up. Our exposure variable was treatment with metformin, which comprised of patients who took metformin for the treatment of type 2 diabetes at any time of diagnosis of metastatic renal cell carcinoma. The outcomes assessed were last available follow-up or date of death for the overall survival and date of progression of disease from their radiological reports for time to progression. The response rates were compared by covariates that are known to be strongly associated with renal cell cancer. ^ Results: For our primary analyses between the insulin and metformin group, there were 82 patients, out of which 50 took insulin therapy and 32 took metformin therapy for type 2 diabetes. For our exploratory analysis, we compared 32 diabetic patients on metformin to 146 non-diabetic patients, not on metformin. Baseline characteristics were compared among the population. The time from the start of treatment until the date of progression of renal cell cancer and date of death or last follow-up were estimated for survival analysis. ^ In our primary analyses, there was a significant difference in the time to progression of patients receiving metformin therapy vs insulin therapy, which was also seen in our exploratory analyses. The median time to progression in primary analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 540 days (95% CI: 350-894) in patients who were receiving insulin therapy (p=0.024). The median time to progression in exploratory analyses was 1259 days (95% CI: 659-1832 days) in patients on metformin therapy compared to 279 days (95% CI: 202-372 days) in non-diabetic group (p-value <0.0001). ^ The median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 816 days (95%CI: 558-1405 days) in insulin group (p-value<0.91). For the exploratory analyses, the median overall survival was 1004 days in metformin group (95% CI: 761-1212 days) compared to 766 days (95%CI: 649-965 days) in the non-diabetic group (p-value<0.78). Metformin was observed to increase the progression free survival in both the primary and exploratory analyses (HR=0.52 in metformin Vs insulin group and HR=0.36 in metformin Vs non-diabetic group, respectively). ^ Conclusion: In laboratory studies and a few clinical studies metformin has been proven to have dual benefits in patients suffering from cancer and type 2-diabetes via its action on the mammalian target of Rapamycin pathway and effect in decreasing blood sugar by increasing the sensitivity of the insulin receptors to insulin. Several studies in breast cancer patients have documented a beneficial effect (quantified by pathological remission of cancer) of metformin use in patients taking treatment for breast cancer therapy. Combination of metformin therapy in patients taking frontline therapy for renal cell cancer may provide a significant benefit in prolonging the overall survival in patients with metastatic renal cell cancer and diabetes. ^

Knowledge of medical abortion among Brazilian medical students

OBJECTIVE: To assess the knowledge of Brazilian medical students regarding medical abortion (MA) and the use of misoprostol for MA, and to investigate factors influencing their knowledge. METHODS: All students from 3 medical schools in São Paulo State were invited to complete a pretested structured questionnaire with precoded response categories. A set of 12 statements on the use and effects of misoprostol for MA assessed their level of knowledge. Of about 1260 students invited to participate in the study, 874 completed the questionnaire, yielding a response rate of 69%. The Ï (2) test was used for the bivariate analysis, which was followed by multiple regression analysis. RESULTS: Although all students in their final year of medical school had heard of misoprostol for termination of pregnancy, and 88% reported having heard how to use it, only 8% showed satisfactory knowledge of its use and effects. Academic level was the only factor associated with the indicators of knowledge investigated. CONCLUSION: The very poor knowledge of misoprostol use for MA demonstrated by the medical students surveyed at 3 medical schools makes the review and updating of the curriculum urgently necessary.

Medication double-checking procedures in clinical practice: a cross-sectional survey of oncology nurses' experiences.

BACKGROUND Double-checking is widely recommended as an essential method to prevent medication errors. However, prior research has shown that the concept of double-checking is not clearly defined, and that little is known about actual practice in oncology, for example, what kind of checking procedures are applied. OBJECTIVE To study the practice of different double-checking procedures in chemotherapy administration and to explore nurses' experiences, for example, how often they actually find errors using a certain procedure. General evaluations regarding double-checking, for example, frequency of interruptions during and caused by a check, or what is regarded as its essential feature was assessed. METHODS In a cross-sectional survey, qualified nurses working in oncology departments of 3 hospitals were asked to rate 5 different scenarios of double-checking procedures regarding dimensions such as frequency of use in practice and appropriateness to prevent medication errors; they were also asked general questions about double-checking. RESULTS Overall, 274 nurses (70% response rate) participated in the survey. The procedure of jointly double-checking (read-read back) was most commonly used (69% of respondents) and rated as very appropriate to prevent medication errors. Jointly checking medication was seen as the essential characteristic of double-checking-more frequently than 'carrying out checks independently' (54% vs 24%). Most nurses (78%) found the frequency of double-checking in their department appropriate. Being interrupted in one's own current activity for supporting a double-check was reported to occur frequently. Regression analysis revealed a strong preference towards checks that are currently implemented at the responders' workplace. CONCLUSIONS Double-checking is well regarded by oncology nurses as a procedure to help prevent errors, with jointly checking being used most frequently. Our results show that the notion of independent checking needs to be transferred more actively into clinical practice. The high frequency of reported interruptions during and caused by double-checks is of concern.

Investigación y análisis sobre la idoneidad de la práctica del tenis de mesa en la Educación Primaria

Esta investigación surge a raíz de la experiencia profesional del autor, maestro especialista de Educación Física en el C.E.I.P. “Alhambra” de Madrid, cuando de manera progresiva, aprecia que el tenis de mesa puede ser un deporte muy interesante de desarrollar en las sesiones de Educación Física y de promover dentro de los tiempos de recreo. El autor cree que este deporte desarrolla una serie de objetivos motrices, afectivos, cognitivos y sociales que pueden contribuir a la adquisición de las competencias básicas y al desarrollo integral de los alumnos. Es entonces cuando recibe formación sobre el deporte de tenis de mesa y busca los medios necesarios de financiación para que se dote al centro del material necesario. Así la Junta municipal del distrito de Fuencarral-El Pardo instala en el patio del colegio tres mesas de exterior y, con los recursos del colegio y la ayuda de la Asociación de padres y madres (AMPA), se consiguen cinco mesas de interior plegables y todo el material necesario (redes, raquetas, pelotas, etc.). Tras introducir este deporte desde 3º a 6º de Educación Primaria promueve un campeonato en el colegio cuyo índice de participación ronda el 90% del alumnado, estos resultados crean al autor ciertas incertidumbres que son la motivación y punto de partida para realizar esta investigación que analice si la práctica del tenis de mesa puede resultar idónea en la etapa de Educación Primaria. Introducción La legislación actual en materia de educación, Ley Orgánica 2/2006, de 3 de mayo, de Educación (LOE) modificada por la Ley Orgánica 8/2013, de 9 de diciembre, para la mejora de la calidad educativa. (LOMCE), otorga una gran relevancia al deporte en general. "El deporte es una actividad saludable, divertida y formativa que puede tener profundos beneficios no sólo para su salud y su bienestar sino también para el desarrollo personal integral físico, psicológico y psicosocial del niño, además de sobre su desarrollo deportivo" (Pradas, 2009, p. 151), es pues, un momento idóneo para analizar qué deportes se practican en los colegios o por qué se practican unos más que otros. "El tenis de mesa además de ser un deporte para todos, se presenta como un juego atractivo, en donde su práctica resulta muy divertida a cualquier edad, tanto para niños como para adultos, principalmente porque presenta unas reglas de juego simples, no encerrando peligro alguno para la integridad física de sus practicantes durante su juego" (Pradas, 2009, p. 83). Es un deporte que "está abierto a todos, sin distinción de edad o sexo, tanto como deporte de alto nivel como de práctica familiar o social" (Gatien, 1993, p. 16). No obstante, "son escasas las obras sobre tenis de mesa. Pocos libros, tanto de divulgación como de reflexión sobre el tenis de mesa, adornan los estantes de las librerías y las bibliotecas" (Erb, 1999, p.14) y añade “así pues, el medio escolar padece de falta de obras explicativas y pedagógicas referidas a este tema" (Erb, 1999, p.14 ) En particular, se pretenden conseguir cinco objetivos divididos en tres categorías (el centro, el profesorado y el deporte. • A nivel de Centro: - Conocer el porcentaje de colegios que disponen de espacios y materiales adecuados para la práctica del tenis de mesa, así como identificar, de las distintas Direcciones de Área Territoriales (DAT), cuál tiene los colegios mejor dotados tanto en instalaciones como en materiales para desarrollar programas de promoción del tenis de mesa. - Averiguar las posibles causas por las que el tenis de mesa no se practica tanto como otros deportes, analizando los impedimentos que limitan la implantación del tenis de mesa como un deporte habitual en los centros de Educación Primaria. Analizar la opinión del profesorado en cuanto a los materiales y las instalaciones necesarios para el tenis de mesa. • A nivel de profesorado: - Analizar el nivel de conocimiento que tienen los profesionales que imparten la asignatura de Educación Física sobre el tenis de mesa, así como sus necesidades para incluir unidades didácticas de tenis de mesa en sus programaciones didácticas. - Conocer el perfil de profesor ideal que recomienda la utilización del tenis de mesa y averiguar el interés del profesorado por recibir formación específica del tenis de mesa. • A nivel de deporte: - Analizar la opinión de los profesionales sobre la idoneidad del tenis de mesa en la Educación Primaria atendiendo a los objetivos que persigue, a las competencias que desarrolla, a los contenidos, criterios de evaluación y estándares de aprendizaje que se pueden trabajar y a las lesiones que se producen. Metodología La investigación se caracterizó por utilizar una metodología inductiva, al surgir de la experiencia profesional del autor, también fue transversal al analizar la realidad en un momento concreto y de tipo cuantitativa. La población objeto de estudio fue la totalidad de los colegios públicos de la Comunidad de Madrid, siendo los profesores de Educación Física los encargados de facilitar los datos solicitados. Estos datos se obtuvieron utilizando como instrumento de toma de datos el cuestionario auto administrado con preguntas cerradas de opción múltiple previamente validado por un panel de 5 expertos. Las variables indirectas fueron: el género del profesorado, la edad del profesorado, la experiencia profesional y el tipo de destino. El proceso de la toma de datos supuso un lapso de tiempo de 3 meses, desde mayo de 2015 hasta julio de 2015, en este tiempo hubo dos fases de recogida de datos, una online a través del correo electrónico institucional de los colegios públicos de la Comunidad de Madrid y otra “in situ” con cuestionarios de lápiz y papel. En cuanto a los datos que se obtuvieron, sobre una población de 798 colegios, se consiguió una muestra de 276, esto supuso una tasa de respuesta del 34,59%, asumiendo la situación más desfavorable posible (p=q) y un nivel de confianza del 95%, para el total de los 276 cuestionarios cumplimentados, el error máximo fue del ±4,78%. Resultados En cuanto a los resultados obtenidos, se establecieron de acuerdo a tres dimensiones: A nivel de Centro, a nivel de Profesorado y a nivel del Deporte y pretendieron averiguar si se alcanzaron los cinco objetivos planteados. Tras el análisis de los resultados, se apreció que los colegios públicos de la Comunidad de Madrid disponían de las suficientes instalaciones para el tenis de mesa, en cambio, faltaban materiales específicos y formación por parte del profesorado, así como recursos didácticos y un programa de promoción del tenis de mesa. Se apreció un manifiesto interés por parte del profesorado en recibir formación específica de tenis de mesa pues la mayoría recomendaba la utilización del tenis de mesa dentro de la asignatura de Educación Física en Educación Primaria. Por último, los resultados mostraron la cantidad de objetivos motrices, afectivos, cognitivos y sociales que desarrolla el tenis de mesa así como su contribución a la adquisición de las competencias básicas y al objetivo “k” de la Educación Primaria, que indica “Valorar la higiene y la salud, conocer y respetar el cuerpo humano, y utilizar la Educación Física y el deporte como medios para favorecer el desarrollo personal y social”, además, se mostró el bajo índice de lesiones que provoca. Discusión y conclusiones El tenis de mesa es un deporte idóneo para ser practicado y enseñado en la asignatura de Educación Física en la etapa de Educación Primaria debido a la gran cantidad de contenidos que son susceptibles de ser trabajados a través de este deporte y debido a la gran cantidad de valores, individuales y sociales que se pueden fomentar con la práctica del tenis de mesa. Las causas de que hasta ahora, el tenis de mesa no sea un deporte practicado de forma habitual en los colegios públicos de la Comunidad de Madrid a pesar de trabajar muchos contenidos específicos de la asignatura de Educación Física puede deberse a factores externos al deporte del tenis de mesa y susceptibles de ser solucionados con una adecuada inversión en materiales específicos, formación del profesorado y recursos didácticos. Si se dota a los centros de los materiales y recursos didácticos necesarios y dando formación al profesorado, éste introduciría unidades didácticas de tenis de mesa dentro de sus programaciones anuales. La federación española y madrileña de tenis de mesa, deberían desarrollar un programa de promoción dotando de materiales y recursos a los centros, tal y como lo han hecho otras federaciones como la de voleibol, bádminton o de baloncesto, entre otras. ABSTRACT This research arises from the professional experience of the author, specialized teacher of physical education in the CEIP "Alhambra" in Madrid, where progressively, appreciates that table tennis can be a very interesting sport to develop in physical education sessions and promote within the playtimes. The author believes that this sport develops a range of motor, affective, cognitive and social objectives that can contribute to the acquisition of basic skills and the integral development of students. It is then when receives training on the sport of table tennis and seeks ways of funding in order to outfit the center with necessary equipment. The Municipal District of Fuencarral-El Pardo installed three outdoor tables in the schoolyard and with the resources of the school and the support of the Association of Parents (AMPA), five indoor folding tables are achieved as well as all the necessary material (nets, rackets, balls, etc.). After introduce the sport from 3rd to 6th grade of primary education, promotes a championship in the school where the participation rate is around 90% of students, these results create the uncertainties to the author that are the motivation and starting point for this research to analyze whether the practice of table tennis can be ideal at the stage of primary education. Introduction The current legislation on education, Organic Law 2/2006 of 3 May, on Education (LOE) as amended by Organic Law 8/2013, of December 9, to improve educational quality (LOMCE), attaches great importance to the sport in general, "Sport is a healthy, funny and educational activity that can have great benefits not only for their health and well-being but also for the physical, psychological and psychosocial comprehensive personal child development besides on their sports development "(Pradas, 2009, p. 151), is therefore an ideal moment to analyze which sports are practiced in schools or why are practiced some more than others. "The table tennis as well as being a sport for everyone, is presented as an attractive game, where its practice is funny at any age, both children and adults, mainly because it has simple game rules, not enclosing danger for the physical integrity of its practitioners during their game" (Pradas, 2009, p. 83). It is a sport that is "open to all, regardless of age or sex, as high-level sport, as family or social practice" (Gatien, 1993, p. 16). However, "there are few books on table tennis. Few books, both reflexion or popularization about table tennis, adorn the shelves of bookstores and libraries." (Erb, 1999, p.14) and add "So, the school environment suffers from lack of explanatory and educational work related to this issue." (Erb, 1999, p.14) In particular, it is intended to achieve the following objectives within the Community of Madrid: • To determine the percentage of schools that have spaces and materials suitable for practicing table tennis and identify, from the different Directorates of Land Area (DAT), which has the best equipped schools in both facilities and materials to develop programs to promote table tennis. • Find out the possible causes that explained why table tennis is not practiced as much as other sports, analyzing impediments that limit the implementation of table tennis as a regular sport in primary schools. Analyze the opinion of teachers in terms of materials and facilities needed for table tennis. • Analyze the level of knowledge about table tennis among professionals who teach the subject of Physical Education and their needs to include teaching units about table tennis in their teaching programs. • Knowing the profile of the ideal teacher who recommends the use of table tennis and figure out the interest of teachers to receive specific training of table tennis. • Analyze the professional opinion on the suitability of table tennis in Primary Education taking into account the objectives pursued, to develop the skills, content, evaluation criteria and learning standards that can work and injuries involved. Methodology The investigation was characterized by using an inductive methodology, arising from the professional experience of the author, was also transverse to analyze reality in a particular time and quantitative type. The population under study were all the state schools in Madrid region, being the physical education teachers responsible for providing the requested data. These data were obtained using as data collection instrument a self-administered questionnaire with multiple choice questions, because it facilitates the analysis thereof. In terms of obtained data, on a population of 798 schools, a sample of 276 was achieved, this represented a response rate of 34.59%, assuming the worst case scenario (p = q) and a level 95% confidence for the total of the 276 completed questionnaires, the maximum error was ± 4.78%. Results In terms of the results, they were set according to three dimensions: center level, professorate level and Sport level and trying to find out whether the five objectives were achieved. After analyzing the results, it was found that schools possessed sufficient facilities for table tennis, however, lacked specific materials and training by teachers, as well as teaching resources and a program to promote table tennis. A clear interest was noticed by teachers in order to receive specific training in table tennis since most recommended the use of table tennis in the subject of physical education in primary education. Finally, the results proved the number of motor, affective, cognitive and social objectives developed by table tennis and its contribution to the acquisition of basic skills and the objective "k" of primary education, in addition to the low rate of injury it causes. Discussion and conclusions Table tennis is an ideal sport to be practiced and taught in the subject of Physical Education in Primary Education due to the large amount of content that are likely to be worked through this sport and due to the large number of individual and social values that can foster the practice of table tennis. The causes of that so far, table tennis is not a sport practiced regularly in schools despite working many specific contents of the subject of Physical Education may be due to factors outside the sport of table tennis and subject to solved with adequate investment in specific materials, teacher training and educational resources. By endowing the centers with the necessary teaching materials and resources and providing training to teachers, they would introduce teaching units of table tennis within their annual programs. Madrid and the Spanish Federation of table tennis should develop a promotional program by endowing materials and resources to the centers, as did other federations such as badminton and basketball, among others.

7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.

We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.