Upper Saddle River, NJ, United States
Upper Saddle River, NJ, United States

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Desai N.R.,Yale University | Desai N.R.,Harvard University | Canestaro W.J.,Harvard University | Canestaro W.J.,University of Washington | And 6 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2013

Background - Patients treated with clopidogrel who have ≥1 loss of function alleles for CYP2C19 have an increased risk for adverse cardiovascular events. In 2010, the US Food and Drug Administration issued a boxed warning cautioning against the use of clopidogrel in such patients. We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for antiplatelet therapy among patients with acute coronary syndrome or percutaneous coronary intervention. Methods and Results - Patients with recent acute coronary syndrome or percutaneous coronary intervention prescribed clopidogrel were offered CYP2C19 testing. Genotype and phenotype results were provided to patients and their physicians, but no specific treatment recommendations were suggested. Patients were categorized based on their genotype (carriers versus noncarriers) and phenotype (extensive, intermediate, and poor metabolizers). The primary outcome was intensification in antiplatelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel. Between July 2010 and April 2012, 6032 patients were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have ≥1 reduced function allele, including 15 (3%) with 2 reduced function alleles. Although reduced function allele carriers were significantly more likely than noncarriers to have an intensification of their antiplatelet therapy, only 20% of poor metabolizers of clopidogrel had their antiplatelet therapy intensified. Conclusions - Providers were significantly more likely to intensify antiplatelet therapy in CYP2C19 allele carriers, but only 20% of poor metabolizers of clopidogrel had an escalation in the dose of clopidogrel or were switched to prasugrel. These prescribing patterns likely reflect the unclear impact and evolving evidence for clopidogrel pharmacogenomics. © 2013 American Heart Association, Inc.

Watters J.,Merck And Co. | Brooks D.,Merck And Co. | Brooks D.,Generation Health | Demuth T.,Merck And Co. | And 6 more authors.
Clinical Cancer Research | Year: 2011

Purpose: Investigate the efficacy and pharmacodynamic effects of MK-1775, a potent Wee1 inhibitor, in both monotherapy and in combination with gemcitabine (GEM) using a panel of p53-deficient and p53 wild-type human pancreatic cancer xenografts. Experimental Design: Nine individual patient-derived pancreatic cancer xenografts (6 with p53-deficient and 3 with p53 wild-type status) from the PancXenoBank collection at Johns Hopkins were treated with MK-1775, GEM, or GEM followed 24 hour later by MK-1775, for 4 weeks. Tumor growth rate/regressions were calculated on day 28. Target modulation was assessed by Western blotting and immunohistochemistry. Results: MK-1775 treatment led to the inhibition of Wee1 kinase and reduced inhibitory phosphorylation of its substrate Cdc2. MK-1775, when dosed with GEM, abrogated the checkpoint arrest to promote mitotic entry and facilitated tumor cell death as compared to control and GEM-treated tumors. MK-1775 monotherapy did not induce tumor regressions. However, the combination of GEM with MK-1775 produced robust antitumor activity and remarkably enhanced tumor regression response (4.01-fold) compared to GEM treatment in p53-deficient tumors. Tumor regrowth curves plotted after the drug treatment period suggest that the effect of the combination therapy is longer-lasting than that of GEM. None of the agents produced tumor regressions in p53 wild-type xenografts. Conclusions: These results indicate that MK-1775 selectively synergizes with GEM to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. ©2011 AACR.

PubMed | Ryerson University, University of Toronto, Generation Health and Indigenous
Type: | Journal: Social science & medicine (1982) | Year: 2016

Striking disparities in Indigenous maternal-child health outcomes persist in relatively affluent nations such as Canada, despite significant health promotion investments. The aims of this review were two-fold: 1. To identify Indigenous prenatal and infant-toddler health promotion programs in Canada that demonstrate positive impacts on prenatal or child health outcomes. 2. To understand how, why, for which outcomes, and in what contexts Indigenous prenatal and infant-toddler health promotion programs in Canada positively impact Indigenous health and wellbeing.We systematically searched computerized databases and identified non-indexed reports using key informants. Included literature evaluated a prenatal or child health promoting program intervention in an Indigenous population in Canada. We used realist methods to investigate how, for whom, and in what circumstances programs worked. We developed and appraised the evidence for a middle range theory of Indigenous community investment-ownership-activation as an explanation for program success.Seventeen articles and six reports describing twenty programs met final inclusion criteria. Program evidence of local Indigenous community investment, community perception of the program as intrinsic (mechanism of community ownership) and high levels of sustained community participation and leadership (community activation) was linked to positive program change across a diverse range of outcomes including: birth outcomes; access to pre- and postnatal care; prenatal street drug use; breast-feeding; dental health; infant nutrition; child development; and child exposure to Indigenous languages and culture.These findings demonstrate Indigenous community investment-ownership-activation as an important pathway for success in Indigenous prenatal and infant-toddler health programs.

PubMed | University of Ottawa, Generation Health, The Newman Breastfeeding Clinic, University of British Columbia and 3 more.
Type: | Journal: BMC pregnancy and childbirth | Year: 2016

Transmasculine individuals are people who were assigned as female at birth, but identify on the male side of the gender spectrum. They might choose to use and engage their bodies to be pregnant, birth a baby, and chestfeed. This study asked an open research question, What are the experiences of transmasculine individuals with pregnancy, birthing, and feeding their newborns?Participants who self-identified as transmasculine and had experienced or were experiencing pregnancy, birth, and infant feeding were recruited through the internet and interviewed. Interviews were transcribed verbatim. We used interpretive description methodology to analyze the data. Our analysis was guided by our awareness of concepts and history important to the transgender community.Out of 22 participants, 16 chose to chestfeed for some period of time, four participants did not attempt chestfeeding, and two had not reached the point of infant feeding (i.e., were still pregnant or had a miscarriage). Nine of the 22 study participants had chest masculinization surgery before conceiving their babies. Six participants had the surgery after their children were born, five desired the surgery in the future, and two did not want it at all. Chest care, lactation, and chestfeeding in the context of being a transgender person are reported in this paper. The participants experiences of gender dysphoria, chest masculinization surgery before pregnancy or after weaning, accessing lactation care as a transmasculine person, and the question of restarting testosterone emerged as data. We present the participants experiences in a chronological pattern with the categories of before pregnancy, pregnancy, postpartum (6weeks post birth), and later stage (beyond 6weeks).The majority of participants chose to chestfeed while some did not due to physical or mental health reasons. Care providers should communicate an understanding of gender dysphoria and transgender identities in order to build patient trust and provide competent care. Further, health care providers need to be knowledgeable about lactation and chest care following chest masculinization surgery and during binding, regardless of the chosen feeding method and through all stages: before pregnancy, during pregnancy, postpartum, and afterward.

Perez-Lopez F.R.,University of Zaragoza | Pasupuleti V.,Case Western Reserve University | Mezones-Holguin E.,Generation Health | Mezones-Holguin E.,Peruvian University of Applied Sciences | And 5 more authors.
Fertility and Sterility | Year: 2015

Objective To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables. Design Systematic review and meta-analysis of randomized controlled trials (RCTs). Setting Not applicable. Patient(s) Pregnant women and neonates. Intervention(s) PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation ± calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy. Main Outcome Measure(s) Measures were: circulating 25-hydroxyvitamin D [25(OH)D] levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs). Result(s) Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH)D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2-66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9-155.3 g) and 0.3 cm (95% CI 0.10-0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous. Conclusion(s) Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion. © 2015 American Society for Reproductive Medicine.

PubMed | University of Otago, National School of Management, Irccs Centro S Giovanni Of Dio Fatebenefratelli, National Institute of Public Health National Institute of Hygiene and 14 more.
Type: Journal Article | Journal: Journal of psychosomatic research | Year: 2015

COPD and mental disorder comorbidity is commonly reported, although findings are limited by substantive weaknesses. Moreover, few studies investigate mental disorder as a risk for COPD onset. This research aims to investigate associations between current (12-month) DSM-IV mental disorders and COPD, associations between temporally prior mental disorders and subsequent COPD diagnosis, and cumulative effect of multiple mental disorders.Data were collected using population surveys of 19 countries (n=52,095). COPD diagnosis was assessed by self-report of physicians diagnosis. The World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) was used to retrospectively assess lifetime prevalence and age at onset of 16 DSM-IV disorders. Adjusting for age, gender, smoking, education, and country, survival analysis estimated associations between first onset of mental disorder and subsequent COPD diagnosis.COPD and several mental disorders were concurrently associated across the 12-month period (ORs 1.5-3.8). When examining associations between temporally prior disorders and COPD, all but two mental disorders were associated with COPD diagnosis (ORs 1.7-3.5). After comorbidity adjustment, depression, generalized anxiety disorder, and alcohol abuse were significantly associated with COPD (ORs 1.6-1.8). There was a substantive cumulative risk of COPD diagnosis following multiple mental disorders experienced over the lifetime.Mental disorder prevalence is higher in those with COPD than those without COPD. Over time, mental disorders are associated with subsequent diagnosis of COPD; further, the risk is cumulative for multiple diagnoses. Attention should be given to the role of mental disorders in the pathogenesis of COPD using prospective study designs.

McAuliffe R.,UISCE Union for Improved Services Communication and Education | Long J.,Generation Health
Irish Journal of Psychological Medicine | Year: 2011

Objective: We describe use and effects of head shop powders among opiate dependant polydrug users and recreational drug users. These powders contain cathinones and were sold as bath salts or plant food via the internet or in head shops. Method: As this is a relatively new phenomenon, a qualitative approach using three data sources, in-depth interviews, a focus group (containing 10 opiate users) and a head shop website containing 49 product reviews, was employed. Themes were identified. Results: According to the study population, these powders mimic the effects of cocaine, ecstasy and amphetamines. These substances were snorted, ingested or injected by people and were not used as bath salts or plant food. The users' experience indicates that these powders have the potential for dependence, and exhibit side effects such as insomnia, anxiety and other mental health effects. The users report that the effects of the substances vary over time indicating that the chemical contents of the powders may change. Conclusion: Though users' descriptions of effects varied, there were indications of health and dependency effects which were more severe and more common among problematic opiate users, who also experienced increased social vulnerability. In general the recreational drug users considered their side effects to be mild and worth the drug induced experience.

de Sonneville-Koedoot C.,Erasmus University Rotterdam | de Sonneville-Koedoot C.,Erasmus Medical Center | Stolk E.A.,Erasmus University Rotterdam | Raat H.,Generation Health | And 2 more authors.
Journal of Fluency Disorders | Year: 2014

Purpose: The purpose of this study is to compare the health-related quality of life (HrQoL) of preschool children who stutter (CWS) and a reference population of children who do not stutter, and to evaluate the association between stuttering severity and HrQoL. Methods: Baseline data were used from 197 children participating in a multicenter Randomized Clinical Trial in the Netherlands. Information on stuttering severity and time since onset (TSO) of stuttering was obtained from the baseline evaluation by speech- and language therapists. Stuttering severity was measured using the SSI-3. HrQoL was assessed using proxy versions of two Child Health Questionnaires (ITQOL-97 and CHQ-PF28), the Health Utility Index 3 (HUI3) and the EuroQoL EQ-VAS (EQ-VAS). Results: While the outcomes on the EQ-VAS and the HUI3 showed that the HrQoL of CWS is slightly poorer than that of the Dutch reference population, results on the different dimensions of the CHQ-instruments did not reveal any difference in scores between stuttering children and reference groups. Within the group of CWS, two ITQOL-97 and four CHQ-PF28 scales showed statistically different scores for children in different SSI stuttering severity or TSO categories. However, the effect sizes showed that these differences were so small that they could be considered negligible. Conclusion: The results of this study do not reveal a diminished HrQoL for preschool CWS. Future research should include a larger cohort of children with severe stuttering, study the longitudinal course of HrQoL and incorporate additional parameters such as the characteristics of the child and his environment.Educational objectives: The reader will be able to: (a) summarize the current evidence base on HrQoL in people who stutter; (b) describe the HrQoL of preschool CWS on different HrQoL measures; (c) describe the relationship between stuttering severity and HrQoL in preschool CWS. © 2014 Elsevier Inc.

PubMed | Generation Health
Type: | Journal: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing | Year: 2016

Reduction of preventable hospital readmissions that result from chronic or acute conditions like stroke, heart failure, myocardial infarction and pneumonia remains a significant challenge for improving the outcomes and decreasing the cost of healthcare delivery in the United States. Patient readmission rates are relatively high for conditions like heart failure (HF) despite the implementation of high-quality healthcare delivery operation guidelines created by regulatory authorities. Multiple predictive models are currently available to evaluate potential 30-day readmission rates of patients. Most of these models are hypothesis driven and repetitively assess the predictive abilities of the same set of biomarkers as predictive features. In this manuscript, we discuss our attempt to develop a data-driven, electronic-medical record-wide (EMR-wide) feature selection approach and subsequent machine learning to predict readmission probabilities. We have assessed a large repertoire of variables from electronic medical records of heart failure patients in a single center. The cohort included 1,068 patients with 178 patients were readmitted within a 30-day interval (16.66% readmission rate). A total of 4,205 variables were extracted from EMR including diagnosis codes (n=1,763), medications (n=1,028), laboratory measurements (n=846), surgical procedures (n=564) and vital signs (n=4). We designed a multistep modeling strategy using the Nave Bayes algorithm. In the first step, we created individual models to classify the cases (readmitted) and controls (non-readmitted). In the second step, features contributing to predictive risk from independent models were combined into a composite model using a correlation-based feature selection (CFS) method. All models were trained and tested using a 5-fold cross-validation method, with 70% of the cohort used for training and the remaining 30% for testing. Compared to existing predictive models for HF readmission rates (AUCs in the range of 0.6-0.7), results from our EMR-wide predictive model (AUC=0.78; Accuracy=83.19%) and phenome-wide feature selection strategies are encouraging and reveal the utility of such datadriven machine learning. Fine tuning of the model, replication using multi-center cohorts and prospective clinical trial to evaluate the clinical utility would help the adoption of the model as a clinical decision system for evaluating readmission status.

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