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A substantial proportion of patients with metastatic castration-resistant prostate cancer were able to receive more than 10 cycles of cabazitaxel without clinically relevant cumulative toxicity.

A substantial proportion of patients with metastatic castration-resistant prostate cancer were able to receive more than 10 cycles of cabazitaxel without clinically relevant cumulative toxicity.

When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children.

The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations-one chewable, one conventional and two dispersible-were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of ired.

Fraction extraction from dispersed aspirin tablets only gave doses within 20% of intended for the dispersible tablets, and then only for some of the manipulation methods 'passive dispersion' for the 75 mg dispersible tablet and 'stirring and pumping' for the 300 mg dispersible tablet. The tablets not intended for dispersion gave unsatisfactory results, outside 20%, regardless of manipulation method. The findings underline the importance of considering both tablet formulation and dose extraction technique when manipulations are required.

Approximately 10% of the general population are reported to have a penicillin allergy, but more than 90% of these patients are able to tolerate penicillins after formal assessment. Patients with penicillin allergy labels have poorer health outcomes and incorrect labels impact negatively on healthcare systems. Identifying patients with incorrect penicillin allergy labels (those who can safely take penicillin) has the potential to benefit patients and healthcare systems. Fluorescein-5-isothiocyanate order This study explores barriers and enablers towards identifying and removing incorrect penicillin allergy labels in inpatients ('delabelling').

Two focus groups were completed with a total of 17 doctors, nurses and pharmacists at a 750-bed district general hospital in England.

Thematic analysis identified four main themes managing penicillin allergic patients, environmental barriers, education for patients and staff and a future delabelling process. Staff reported that identifying and delabelling incorrect penicillin allergy records was a crecognised as a complex problem. A patient pathway involving nurses, doctors and pharmacist is likely to be the optimal method to safely delabel patients.

The main objective was to identify all studies that present data regarding microbial contamination of vials used for preparation with closed-system drug transfer devices (CSTDs). Our secondary objective was to compare the reported contamination of vials punctured with a CSTD versus no CSTD and to evaluate the quality of data reporting as defined by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.

A literature review was conducted on 31 December 2018 on PubMed, EMBASE and Cumulative Index to Nursing and Allied Health Literature. A manual search of the archives of relevant pharmaceutical conferences was made. All studies that presented data about microbial contamination of vials punctured with a CSTD or about beyond-use date extension were included. Two researchers independently graded the articles according to the STROBE criteria.

Of the 280 articles identified initially, 12 were retained for analysis. Studies evaluated microbial contamination according to diffewed a significant difference between vials punctured with a CSTD and with a conventional method. Centre-specific sterility testing is needed to reflect the variability of handling procedures and equipment.Treatment regimens for pediatric Hodgkin lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of 18F-FDG PET/MRI with a 18F-FDG PET/CT reference standard for staging and response assessment. Methods Twenty-four patients (mean age, 15.4 y; range, 8-19.5 y) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both 18F-FDG PET/CT and 18F-FDG PET/MRI at initial staging (n = 24) and at response assessment (n = 21). The diagnostic accuracy of 18F-FDG PET/MRI for both nodal and extranodal disease was compared with that of 18F-FDG PET/CT, which was considered the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors, and 18F-FDG PET/MRI and 18F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann Arbor staging and Deauville grading was also assessed. Results For nodal and extranodal sites combined, corrected staging 18F-FDG PET/MRI sensitivity was 100% (95% CI, 96.7%-100%) and specificity was 99.5% (95% CI, 98.3%-99.9%). link2 Corrected response-assessment 18F-FDG PET/MRI sensitivity was 83.3% (95% CI, 36.5%-99.1%) and specificity was 100% (95% CI, 99.2%-100%). Modified Ann Arbor staging agreement between 18F-FDG PET/CT and 18F-FDG PET/MRI was perfect (κ = 1.0, P = 0.000). Deauville grading agreement between 18F-FDG PET/MRI and 18F-FDG PET/CT was excellent (κ = 0.835, P = 0.000). Conclusion 18F-FDG PET/MRI is a promising alternative to 18F-FDG PET/CT for staging and response assessment in children with HL.This article explores basic statistical concepts of clinical trial design and diagnostic testing, or how one starts with a question, formulates it into a hypothesis on which a clinical trial is then built, and integrates it with statistics and probability, such as determining the probability of rejecting the null hypothesis when it is actually true (type I error) and the probability of failing to reject the null hypothesis when it is false (type II error). There are a variety of tests for different types of data, and the appropriate test must be chosen for which the sample data meet the assumptions. Correcting type I error in the presence of multiple testing is needed to control the error's inflation. Within diagnostic testing, identifying false-positive and false-negative results is critical to understanding the performance of a test. These are used to determine the sensitivity and specificity of a test along with the test's negative predictive value and positive predictive value. These quantities, specifically sensitivity and specificity, are used to determine the accuracy of a diagnostic test using receiver-operating-characteristic curves. These concepts are briefly introduced to provide a basic understanding of clinical trial design and analysis, with references to allow the reader to explore various concepts at a more detailed level if desired.PET with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods This prospective, single-arm, 2-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2-4 mo after starting therapy. Patients were followed for up to 48 mo from enrollment. A central review evaluated baseline and follow-up PET scans, recording change in SUVmax at all disease sites and classifying the pattern of change. Two parameters were derived the δ-percent SUVmax (DPSM) of all lesions and the δ-absolute SUVmax (DASM) of all lesions. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results Sixteen evaluable patients were accrued to the study. link3 Median TTTC was 9.6 mo (95% CI, 6.9-14.2), and median OS was 28.6 mo (95% CI, 18.3-not available [NA]). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had a shorter TTTC and OS. Men with a low DPSM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of 37.2 mo (95% CI, 28.9-NA), whereas those with a high DPSM had a median TTTC of 6.5 mo (95% CI, 4.6-NA, P = 0.0001) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.02). Men with a low DASM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of NA (95% CI, 37.2 mo-NA), whereas those with a high DASM had a median TTTC of 6.9 mo (95% CI, 6.1-NA, P = 0.003) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.002). Conclusion Findings on PSMA-targeted PET 2-4 mo after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.The liver is a major metabolic organ that regulates the whole-body metabolic homeostasis and controls hepatocyte proliferation and growth. The ATF/CREB family of transcription factors integrates nutritional and growth signals to the regulation of metabolism and cell growth in the liver, and deregulated ATF/CREB family signaling is implicated in the progression of type 2 diabetes, nonalcoholic fatty liver disease, and cancer. This article focuses on the roles of the ATF/CREB family in the regulation of glucose and lipid metabolism and cell growth and its importance in liver physiology. We also highlight how the disrupted ATF/CREB network contributes to human diseases and discuss the perspectives of therapeutically targeting ATF/CREB members in the clinic.A novel clustering approach identified five subgroups of diabetes with distinct progression trajectories of complications. We hypothesized that these subgroups differ in multiple biomarkers of inflammation. Serum levels of 74 biomarkers of inflammation were measured in 414 individuals with recent adult-onset diabetes from the German Diabetes Study (GDS) allocated to five subgroups based on data-driven cluster analysis. Pairwise differences between subgroups for biomarkers were assessed with generalized linear mixed models before (model 1) and after (model 2) adjustment for the clustering variables. Participants were assigned to five subgroups severe autoimmune diabetes (21%), severe insulin-deficient diabetes (SIDD) (3%), severe insulin-resistant diabetes (SIRD) (9%), mild obesity-related diabetes (32%), and mild age-related diabetes (35%). In model 1, 23 biomarkers showed one or more pairwise differences between subgroups (Bonferroni-corrected P less then 0.0007). Biomarker levels were generally highest in SIRD and lowest in SIDD.

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