Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial.

BACKGROUND: Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib's efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination-deficient tumors. METHODS: OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator's discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator's discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination-deficient. The primary endpoint is the pre-interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1. DISCUSSION: OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination-deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.

Air pollutants and attention deficit hyperactivity disorder medication administration in elementary schools.

Air pollution is considered a risk factor for several diseases, particularly respiratory and cardiovascular diseases. However, the effects of air pollution on neurobehavioral disorders have not been confirmed as of yet. Thus, the aim of this study was to determine whether there was an association between seven air pollutants and ADHD medication administration (ADHD-MA) in Pennsylvania-located elementary schools over a 3-year period. An ecological study design involving records of 168,825 children from elementary schools in 49 Pennsylvania counties was used. The number of children with ADHD-MA was extracted from an online software specifically designed for allowing nurses to record health conditions in schools. Daily measurements of air pollutants were obtained from the U.S Environmental Protection Agency. The differences in the number of ADHD-MA among the four seasons, for all years, were statistically significant (P<0.001). Three air pollutants (SO2, CO, and PM2.5) were significantly associated with ADHD-MA; no interactions among air pollutants were significant. Air pollution was thus likely associated with ADHD-MA. Prospective epidemiological and biomedical studies should next examine the molecular relationship between air pollution and ADHD symptoms.

Attenuated PTH responsiveness to vitamin D deficiency among patients with type 2 diabetes and chronic hyperglycemia.

BACKGROUND: The short and long-term relationship between hyperglycemia and PTH level among patients suffering from both diabetes type 2 and vitamin D deficiency were evaluated. METHODS: This was a cross sectional study performed at Dubai Diabetes Center, UAE. To demonstrate the relationship between hyperglycemia and PTH level, subjects with type 2 diabetes and vitamin D deficiency (124 adults) were divided into 4 groups based on their FPG and HbA1c levels. RESULTS: Mean vitamin D and PTH levels among subjects with HbA1c≤7% (53mmol/mol) were 14.05ng/ml and 19.51pg/ml respectively. On the other hand, mean vitamin D and PTH levels among subjects with HbA1c≥10% (86mmol/mol) were significantly lower at 11.77ng/ml and 17.75pg/ml respectively. The product of vitamin D and PTH among subjects with an HbA1c≤7% (53mmol/mol) was 250.380, compared with only 197.710 among subjects with HbA1c≥10 (86mmol/mol). Regression analysis for subjects older than 50years shows a significant negative effect of HbA1c on the PTH level. Mean calcium level among subjects with HbA1c≤7% (53mmol/mol) was 8.80mg/dl compared with 8.94mg/dl when HbA1c is ≥10% (86mmol/mol) with no statistical difference. Although high FPG was associated with a lower PTH level, such association was not statistically significant. CONCLUSIONS: Chronic hyperglycemia, as assessed by A1C level, is associated with a significantly attenuated PTH responsiveness to vitamin D deficiency without a significant change in calcium level. On the other hand, there was no significant association between FPG and PTH level.

Discrepant body mass index: behaviors associated with height and weight misreporting among US adolescents from the National Youth Physical Activity and Nutrition Study.

BACKGROUND: The accuracy and reliability of self-reported height and weight among adolescents in the process of calculating BMI is usually subject to bias. The aim of this study was to determine whether over- and under-reporting of self-reported height and weight existed among US high school students by weight category; if so, to examine anthropometric, behavioral, and demographic factors associated with over- and under-reporting. METHODS: Data were retrieved from the National Youth Physical Activity and Nutrition Study, 2010, a nationally representative sample (7160 students, grades 9-12). Analysis of variance was performed to determine any significant difference between weight categories in misreporting. Discriminant function analysis and sequential logistic regression were executed to detect behavioral and demographic predictors of reporting accuracy, respectively. RESULTS: The mean over-reporting of height and under-reporting of weight were 1.1 cm and 1.020 kg, respectively, which underestimated BMI and BMI percentile by 0.671 and 2.734, respectively. Use of self-reported height and weight for BMI calculation overestimated prevalence of healthy weight by 3.8% and underestimated prevalence of obesity by 4.1%. Underweight students under-reported height and over-reported weight, whereas overweight and obese students over-reported height and under-reported weight. Reporting accuracy of females was significantly higher. Weight loss behaviors, both healthy and unhealthy, were associated with BMI underestimation, whereas fast foods and screen time were associated with overestimation. CONCLUSION: Whenever possible, measuring height and weight is essential. However, because many studies must rely on self-reported values alone, additional research should examine the relationships between misreport of anthropometric data and lifestyle features in diverse adolescent samples to better interpret self-reported anthropometric data.

Trends in body mass index and prevalence of extreme high obesity among Pennsylvania children and adolescents, 2007-2011: promising but cautionary.

OBJECTIVES: We determined current trends and patterns in overweight, obesity, and extreme high obesity among Pennsylvania pre-kindergarten (pre-K) to 12th grade students and simulated future trends. METHODS: We analyzed body mass index (BMI) of pre-K to 12th grade students from 43 of 67 Pennsylvania counties in 2007 to 2011 to determine trends and to discern transition patterns among BMI status categories for 2009 to 2011. Vinsem simulation, confirmed by Markov chain modeling, generated future prevalence trends. RESULTS: Combined rates of overweight, obesity, and extreme high obesity decreased among secondary school students across the 5 years, and among elementary students, first increased and then markedly decreased. BMI status remained constant for approximately 80% of normal and extreme high obese students, but both decreased and increased among students who initially were overweight and obese; the increase in BMI remained significant. CONCLUSIONS: Overall trends in child and adolescent BMI status seemed positive. BMI transition patterns indicated that although overweight and obesity prevalence leveled off, extreme high obesity, especially among elementary students, is projected to increase substantially over time. If current transition patterns continue, the prevalence of overweight, obesity, and extreme high obesity among Pennsylvania students in 2031 is projected to be 16.0%, 6.6%, and 23.2%, respectively.

Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

OBJECTIVES: This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. METHODS: Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. RESULTS: The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. CONCLUSIONS: Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

Prediction of asthma exacerbations among children through integrating air pollution, upper atmosphere, and school health surveillances.

Climatic factors and air pollution are important in predicting asthma exacerbations among children. This study was designed to determine if a relationship exists between asthma exacerbations among elementary school children and the combined effect of daily upper atmosphere observations (temperature, relative humidity, dew point, and mixing ratio) and daily air pollution (particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) and, if so, to predict asthma exacerbations among children using a mathematical model. Using an ecological study design, school health records of 168,825 students in elementary schools enrolled in "Health eTools for Schools" within 49 Pennsylvania counties were analyzed. Data representing asthma exacerbations were originally recorded by school nurses as the type of treatment given to a student during a clinic visit on a particular day. Daily upper atmosphere measurements from ground level to the 850-mb pressure level and air pollution measurements were obtained. A generalized estimating equation model was used to predict the occurrence of >48 asthma exacerbations, the daily mean for 2008-2010. The greatest occurrence of asthma among school children was in the fall, followed by summer, spring, and winter. Upper atmosphere temperature, dew point, mixing ratio, and six air pollutants as well as their interactions predicted the probability of asthma exacerbations occurring among children. Monitoring of upper atmosphere observation data and air pollutants over time can be a reliable means for predicting increases of asthma exacerbations among elementary school children. Such predictions could help parents and school officials implement effective precautionary measures.

Use of data mining to reveal body mass index (BMI): patterns among Pennsylvania schoolchildren, pre-k to grade 12.

BACKGROUND: Health eTools for Schools was developed to assist school nurses with routine entries, including height and weight, on student health records, thus providing a readily accessible data base. Data-mining techniques were applied to this database to determine if clinically significant results could be generated. METHODS: Body mass index (BMI) data collected and entered in eTools by school nurses from 657,068 students attending 1156 schools in 49 of 67 Pennsylvania counties during 2005-2009 were analyzed. Students in each BMI category were sorted; regression was used to model mean and percentage trends. A chi-square test of individually matched BMI percentages was computed and migration across normal, overweight, and obese states determined. RESULTS: The highest percentage of obese students occured in middle school. The mean trends for obesity and overweight had increasing slopes of 0.189 and 0.227, respectively; with regression slope for overweight >59%. Within groups, substantial percentages of individually matched BMIs changed significantly (p < .0001) over 2 years, migrating between normal weight, overweight, and obese. A comparison of 2009 measured BMI for grades 9-12 from eTools with 2009 Pennsylvania Youth Risk Behavior Survey self-reported BMI yielded substantial diferences. CONCLUSION: A pattern of increasing BMI for elementary students with a corresponding decrease among middle and high school students emerged. The means trends for both overweight and obesity were greater in 2009 than in 2005, increasing steadily to 2008 and slightly declining to 2009. The dominant overall pattern flows from overweight to obese. If continued unabated, percentage of students who are obese will dominate over time.

Psychological distress among nurses caring for victims of war in Sri Lanka.

OBJECTIVE: To determine prevalence and factors associated with psychological distress among nurses caring for war victims in Sri Lanka. METHODS: Descriptive, cross-sectional study design was used to collect data from 241 nurses from 2 hospitals with stratified random sampling according to workstation. Self-administered 30-item General Health Questionnaire was used to detect psychological distress. RESULTS: The prevalence of psychological distress was 21%. Female sex was found to be the most significant predictor of psychological distress among nurses. Factors, such as being married, having children, or both, were found to be protective. High exposure to war victims, measured by the frequency with which a nurse tended to those patients, also resulted in less psychological distress. CONCLUSIONS: The prevalence of psychological distress is higheramong nurses in this study compared with that among the general population. Brief screening instruments, such as the General Health Questionnaire, can be used to identify individuals at risk for psychological distress. Results suggest that the presence of a social support network helped to psychologically buffer these nurses. Findings also imply the importance of promoting positive attitudes and beneficial stress (eustress) to complement a well-developed focus on distress prevention.

Air pollution indicators predict outbreaks of asthma exacerbations among elementary school children: integration of daily environmental and school health surveillance systems in Pennsylvania.

Objectives of this study are to determine if a relationship exists between asthma exacerbations among elementary school children in industrialized countries (with climatic seasons) and exposure to daily air pollution with particulate matter, sulfur dioxide, nitrogen dioxide, nitrogen oxides, carbon monoxide, and ozone, when controlled for potential confounders; and, if so, to derive a statistical model that predicts variation of asthma exacerbations among elementary school children. Using an ecological study design, health records of 168,25 students from elementary schools in 49 Pennsylvania counties employing "Health eTools for Schools" were analyzed. Asthma exacerbations were recorded by nurses as treatment given during clinic visits each day. Daily air pollution measurements were obtained from the EPA's air quality monitoring sites. The distribution of asthmatic grouping for pollen and calendar seasons was developed. A Poisson regression model was used to predict the number of asthma exacerbations. The greatest occurrence of asthma exacerbations was in autumn, followed by summer, spring and winter. If the number of asthma exacerbations on a day is N and the daily mean of asthma exacerbations for the three-year period is 48, the probabilities of N > 48 in tree pollen and grass pollen seasons were 56.5% and 40.8%, respectively (p < 0.001). According to the Poisson regression, the week number and prior day CO, SO2, NO2, NOx, PM2.5, and O3 had significant effects on asthma exacerbations among students. Monitoring of air pollutants over time could be a reliable new means for predicting asthma exacerbations among elementary school children. Such predictions could help parents and school nurses implement effective precautionary measures.

Upper-air observation indicators predict outbreaks of asthma exacerbations among elementary school children: integration of daily environmental and school health surveillance systems in Pennsylvania.

OBJECTIVE: To determine whether a relationship exists between asthma exacerbations among elementary school children and daily upper-air observations (temperature, relative humidity, dew point, and mixing ratio) and, if so, to derive a mathematical model that predicts asthma exacerbations among children. METHODS: Using an ecological study design, school health records of 168,825 elementary school students enrolled in the Health eTools for Schools program within 49 Pennsylvania counties were analyzed. Data representing asthma exacerbations were originally recorded by school nurses as the type of treatment given to a student during a clinic visit on a particular day. Daily upper-air measurements from ground level to the 850 mb pressure level, covering a radius of 800 km around Pittsburgh, PA, were obtained. The Wilcoxon two-sample test was used to identify associations. A generalized estimating equation model was used to predict the occurrence of more than 48 asthma exacerbations, the daily mean for 2008-2010. RESULTS: Surveillance of asthma among school children in Pennsylvania increased over 3 years. The greatest occurrence was in the fall, followed by summer, spring, and winter. Annual averages of upper-air observations were significantly different between seasons (p < .02). Upper-air temperature, dew point, and mixing ratio above their 3-year mean values and upper-air relative humidity ≥ 50% were significantly associated with occurrence of asthma exacerbations (p < .011). CONCLUSIONS: Monitoring of upper-air observation data over time can be a reliable means for predicting increases of asthma exacerbations among elementary school children. Such predictions could help parents and school nurses implement effective precautionary measures.

Catalyzing transdisciplinary studies in public health: a college health survey and data platform.

Researchers, educators, and service providers recognize that health behaviors and conditions are interdependent, yet they are too often addressed compartmentally. This "silo" approach is unfortunate because it leads to inefficiencies and less effective approaches to prevention. This article describes a process designed to promote better understanding of the interrelatedness of health behaviors and outcomes through a multidimensional Internet-based health survey aimed at undergraduate college students. In addition, we describe a data-sharing platform whereby faculty and students from across disciplines may access the raw data for a variety of uses. An analysis is performed illustrating a syndemic between binge drinking, sexually transmitted diseases, and using alcohol or drugs prior to sexual intercourse. Potential applications of the multidomain survey are discussed, as well as lessons learned and limitations of this approach.

Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol.

BACKGROUND: A derived peptide from activity-dependent neurotrophic factor (ADNF-9) has been shown to be neuroprotective in the fetal alcohol exposure model. We investigated the neuroprotective effects of ADNF-9 against alcohol-induced apoptosis using TUNEL staining. We further characterize in this study the proteomic architecture underlying the role of ADNF-9 against ethanol teratogenesis during early fetal brain development using liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS). METHODS: Pregnant C57BL/6 mice were exposed from embryonic days 7-13 (E7-E13) to a 25% ethanol-derived calorie [25% EDC, Alcohol (ALC)] diet, a 25% EDC diet simultaneously administered i.p. ADNF-9 (ALC/ADNF-9), or a pair-fed (PF) liquid diet. At E13, fetal brains were collected from 5 dams from each group, weighed, and frozen for LC-MS/MS procedure. Other fetal brains were fixed for TUNEL staining. RESULTS: Administration of ADNF-9 prevented alcohol-induced reduction in fetal brain weight and alcohol-induced increases in cell death. Moreover, individual fetal brains were analyzed by LC-MS/MS. Statistical differences in the amounts of proteins between the ALC and ALC/ADNF-9 groups resulted in a distinct data-clustering. Significant upregulation of several important proteins involved in brain development were found in the ALC/ADNF-9 group as compared to the ALC group. CONCLUSION: These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.

Prevention of dengue Fever: an exploratory school-community intervention involving students empowered as change agents(*).

BACKGROUND: Dengue fever and dengue hemorrhagic fever (DF/DHF) are epidemic and endemic in tropical and subtropical countries including Sri Lanka. Numerous structural and community interventions have been shown to be effective in interrupting the life cycle of mosquitoes that transmit DF/DHF; however, these interventions are not always implemented intensely and/or consistently enough to control the mosquito populations and suppress the disease. Following a planned and systematic training and mobilizing program, in conjunction with a public information campaign, seventh-, eighth-, and ninth-grade students in 2 schools performed multiple mosquito control and education interventions in their communities once a week for 8 weeks. METHODS: Five actions identified in previous literature and executed by students were tracked and secondary entomology data were obtained from public health surveillance systems. The Z-test for determining differences between proportions was utilized to determine significant changes between pre- and post-entomological survey findings in 2 intervention areas, 1 rural and 1 urban. Pre- and post-incidence rates from the intervention areas and comparable control areas were compared. RESULTS: In intervention areas, all proportions of larval indexes were found to be significantly lower following the intervention. Surveillance data showed a 73% reduction in case load for the urban area and a 61% reduction in the rural area during the year following intervention. CONCLUSION: If properly involved and guided, school children can be an asset to mosquito-borne disease control; the education sector could be an important partner in DF/DHF control.

Adjuvant chemotherapy for breast cancer: how presentation of recurrence risk influences decision-making.

PURPOSE: The purpose of this study was to examine the impact of four methods of communicating survival benefits on chemotherapy decisions. We hypothesized that the four methods of communicating mathematically equivalent risk information would lead to different chemotherapy decisions. METHODS: Each participant received two hypothetical scenarios regarding their mother (a postmenopausal woman with an invasive, lymph node-negative, hormone receptor-positive breast cancer) and was asked to decide whether they would encourage their mother to take chemotherapy in addition to surgery and tamoxifen. In the part 1, participants received one of four methods of describing the chemotherapy survival benefit: (1) relative risk reduction, (2) absolute risk reduction, (3) absolute survival benefit, or (4) number needed to treat. In part 2, each participant received all four methods. Following each decision, participants were asked to rate their confidence and confusion regarding their decision. RESULTS: Participants included 203 preclinical medical students. In part 1, participants who received relative risk reduction information were significantly more likely to endorse chemotherapy. In part 2, there were no treatment decision differences when participants received all four methods of communicating survival benefits of chemotherapy. However, receiving all four methods led to significantly higher ratings of confusion. In deciding on endorsing chemotherapy, participants understood the information best when presented with data in the absolute survival benefit format. CONCLUSION: These results support the hypothesis that the method used to present information about chemotherapy influences treatment decisions. Absolute survival benefit is the most easily understood method of conveying the information regarding benefit of treatment.