Pharmacokinetics of vibunazole (Bay n7133) administered orally to healthy subjects

Contains fulltext : 4447.pdf (publisher's version ) (Open Access

Non-adherence to consensus guidelines on preoperative imaging in surgery for primary hyperparathyroidism

Objective: The aim of this study was to determine the adherence to consensus guidelines on preoperative imaging of patients with primary hyperparathyroidism (pHPT) in real local practice. Methods: This was a retrospective multicenter cohort study of 411 patients undergoing parathyroidectomy for pHPT from 2007 to 2017 in three referral centers. Results: In 286/411 patients (69%) the preoperative imaging workup adhered to guidelines (utilizing ultrasound and parathyroid scintigraphy). In patients in whom guidelines were followed 63% were discharged within one day versus 37% in whom guidelines were not followed (P< .0005). The use of a bimodality imaging workup, starting with ultrasound and parathyroid scintigraphy followed by imaging upscaling aiming for anatomical and functional concordance, was a predictor for the performance of a minimally invasive parathyroidectomy (OR 4.098, 95% CI 2.296-7.315,P< .0005). Conclusion: The level of compliance to preoperative imaging guidelines is suboptimal in this population. Patients in whom adherence was achieved showed a shorter length of stay. More education of physicians is required regarding the appropriate preoperative imaging workup in pHPT

Incorporating Primary and Secondary Prevention Approaches To Address Childhood Obesity Prevention and Treatment in a Low-Income, Ethnically Diverse Population: Study Design and Demographic Data from the Texas Childhood Obesity Research Demonstration (TX CORD) Study

Background: There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demonstration (TX CORD) project, which addresses child obesity among low-income, ethnically diverse overweight and obese children, ages 2–12 years; a two-tiered systems-oriented approach is hypothesized to reduce BMI z-scores, compared to primary prevention alone. Methods: Our study aims are to: (1) implement and evaluate a primary obesity prevention program; (2) implement and evaluate efficacy of a 12-month family-centered secondary obesity prevention program embedded within primary prevention; and (3) quantify the incremental cost-effectiveness of the secondary prevention program. Baseline demographic and behavioral data for the primary prevention community areas are presented. Results: Baseline data from preschool centers, elementary schools, and clinics indicate that most demographic variables are similar between intervention and comparison communities. Most families are low income ( \u3c $25,000) and Hispanic/Latino (73.3– 83.8%). The majority of parents were born outside of the United States. Child obesity rates exceed national values, ranging from 19.0% in preschool to 35.2% in fifth-grade children. Most parents report that their children consume sugary beverages, have a television in the bedroom, and do not consume adequate amounts of fruits and vegetables. Conclusions: Interventions to address childhood obesity are warranted in low-income, ethnically diverse communities. Integrating primary and secondary approaches is anticipated to provide sufficient exposure that will lead to significant decreases in childhood obesity

Incorporating Primary and Secondary Prevention Approaches To Address Childhood Obesity Prevention and Treatment in a Low-Income, Ethnically Diverse Population: Study Design and Demographic Data from the Texas Childhood Obesity Research Demonstration (TX CORD) Study

Background: There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demonstration (TX CORD) project, which addresses child obesity among low-income, ethnically diverse overweight and obese children, ages 2–12 years; a two-tiered systems-oriented approach is hypothesized to reduce BMI z-scores, compared to primary prevention alone. Methods: Our study aims are to: (1) implement and evaluate a primary obesity prevention program; (2) implement and evaluate efficacy of a 12-month family-centered secondary obesity prevention program embedded within primary prevention; and (3) quantify the incremental cost-effectiveness of the secondary prevention program. Baseline demographic and behavioral data for the primary prevention community areas are presented. Results: Baseline data from preschool centers, elementary schools, and clinics indicate that most demographic variables are similar between intervention and comparison communities. Most families are low income ( \u3c $25,000) and Hispanic/Latino (73.3– 83.8%). The majority of parents were born outside of the United States. Child obesity rates exceed national values, ranging from 19.0% in preschool to 35.2% in fifth-grade children. Most parents report that their children consume sugary beverages, have a television in the bedroom, and do not consume adequate amounts of fruits and vegetables. Conclusions: Interventions to address childhood obesity are warranted in low-income, ethnically diverse communities. Integrating primary and secondary approaches is anticipated to provide sufficient exposure that will lead to significant decreases in childhood obesity

Computational toxicology using the OpenTox application programming interface and Bioclipse

BACKGROUND: Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. FINDINGS: This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. CONCLUSIONS: A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers

Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis

Introduction: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. Methods: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. Results: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2–8.7) years and 5.7 (IQR 4.8–8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). Conclusions: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup

Sars-Cov-2 Serostatus and Covid-19 Illness Characteristics By Variant Time Period in Non-Hospitalized Children and adolescents

OBJECTIVE: to describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample. DESIGN: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old. SETTING: State of Texas, USA. PARTICIPANTS: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOME(S) AND MEASURE(S): SARS-CoV-2 antibody status was assessed by the Roche Elecsys RESULTS: Over half (57.2%) of the sample (N = 3911) was antibody positive. Symptomatic infection increased over time from 47.09% during the pre-Delta variant time period, to 76.95% during Delta, to 84.73% during Omicron, and to 94.79% during the Omicron BA.2. Those who were not vaccinated were more likely (OR 1.71, 95% CI 1.47, 2.00) to be infected versus those fully vaccinated. CONCLUSIONS: Results show an increase in symptomatic COVID-19 infection among non-hospitalized children with each progressive variant over the past two years. Findings here support the public health guidance that eligible children should remain up to date with COVID-19 vaccinations

Mining Biological Pathways Using WikiPathways Web Services

WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process

Methodology to Estimate Natural- and Vaccine-induced antibodies to Sars-Cov-2 in a Large Geographic Region

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning September 30, 2020. Along with state vaccination data, as of October 31, 2021, the estimated percentage of those 5 years or older with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.0% (95% CI = (33.1%, 36.9%)). This is 3× higher than, state-confirmed COVID-19 cases (11.83%) for all ages. The percentage with naturally occurring or vaccine-induced antibodies (total seroprevalence) is 77.42%. This methodology is integral to pandemic preparedness as accurate estimates of seroprevalence can inform policy-making decisions relevant to SARS-CoV-2