A Multicentre Retrospective Analysis of Toxicity in 6-weekly Versus 3-weekly Pembrolizumab.

Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor with a dosing schedule of 200 mg 3 weekly (q3w). Dose of 400 mg 6 weekly (q6w) was approved based on simulation of dose/exposure relationships and predicted no difference in toxicity. We present real-world comparative toxicity data. Patients receiving pembrolizumab for any indication between March and December 2019 were included across 3 regional centers. Toxicity data were collected retrospectively using Common Terminology Criteria for Adverse Events, v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and grade ≥3 rash. Data were analyzed using incidence (Poisson distribution) and incidence ratio. Overall, 63 patients started on q6w and 110 patients received q3w. There were 3 (q6w) and 8 (q3w) grade 3-5 CSirAE and 13 (q6w) and 31 (q3w) grade 1-2 CSirAE. The incidence of grade 3-5 CSirAE was 0.77 (95% confidence interval: 0.16-2.24) per 100 patient-months in q6w and 0.68 (95% confidence interval: 0.29-1.34) per 100 patient-months in q3w (incidence ratio of 1.13; 95% confidence interval: 0.19-4.70). Low-grade toxicity was common (fatigue, pruritus, rash; q6w 46%, q3w 42%). Incidence of CSirAEs was low but low-grade toxicity was common. Despite a limited number of events, there is the suggestion that the q6w schedule has a similar toxicity profile to q3w and therefore consideration should be given to the reduced burden to patients and health services when deciding treatment.

Development and Dissemination of the El Centro Health Disparities Measures Library.

PURPOSE: This report describes the development and dissemination of a library of English measures, with Spanish translations, on constructs relevant to social determinants of health and behavioral health outcomes. The El Centro Measures Library is a product of the Center of Excellence for Health Disparities Research: El Centro, a program funded by the National Institute on Minority Health and Health Disparities of the U.S. National Institutes of Health. The library is aimed at enhancing capacity for minority health and health disparities research, particularly for Hispanics living in the United States and abroad. DESIGN: The open-access library of measures (available through www.miami.edu/sonhs/measureslibrary) contains brief descriptions of each measure, scoring information (where available), links to related peer-reviewed articles, and measure items in both languages. Links to measure websites where commercially available measures can be purchased are included, as is contact information for measures that require author permission. Links to several other measures libraries are hosted on the library website. Other researchers may contribute to the library. METHODS: El Centro investigators began the library by electing to use a common set of measures across studies to assess demographic information, culture-related variables, proximal outcomes of interest, and major outcomes. The collection was expanded to include other health disparity research studies. In 2012, a formal process was developed to organize, expand, and centralize the library in preparation for a gradual process of dissemination to the national and international community of researchers. FINDINGS: The library currently contains 61 measures encompassing 12 categories of constructs. Thus far, the library has been accessed 8,883 times (unique page views as generated by Google Analytics), and responses from constituencies of users and measure authors have been favorable. CLINICAL RELEVANCE: With the paucity of availability and accessibility of translated measures, behavioral nursing research focused on reducing health disparities can benefit from repositories of research instruments such as the El Centro Measures Library.

New hydroxy-pyrazoline intermediates, subtle regio-selectivity and relative reaction rate variations observed during acid catalyzed and neutral pyrazole cyclization.

Arylhydrazines 4 and 1,3-dicarbonyl compounds 5 react to form pyrazoles by loss of water via hydrazone isomer pairs 6 and 7 which give rise to two possible regio-isomers. Occasionally, 3-hydroxy-3,4-dihydropyrazoles or hydroxy-pyrazolines 9 and 9 are observed as stable isolatable intermediates that can be fully characterized prior to loss of the second molecule of water that gives rise to pyrazoles 10 and 11. Fully characterized examples of intermediates of type 8 and 9 are relatively rare. We studied the reaction series where R = CH3, CHF2 and CF3 and Ar = Ph and 5-methanesulfonylpyridin-2-yl, (Scheme 2), and observed differences in properties between kinetic behavior and regio-isomerism depending on the degree of electron-withdrawing capability of the R and Ar substituents. The reaction conditions that caused cyclization to pyrazoles varied from direct condensation of the hydrazine and 1,3-dicarbonyl compounds, to reactions requiring catalytic quantities of sulfuric acid to sulfuric acid in excess. Unexpected regio-selectivity was observed in the case of R = CF3 that depended upon the reaction conditions.

Thromboprophylaxis in medical patients: the role of low-molecular-weight heparin.

Many hospitalised medical patients are at increased risk of venous thromboembolism (VTE). Consensus statements recommend that such patients be assessed for risk of VTE on admission to hospital and receive thromboprophylaxis where appropriate. However, VTE prophylaxis is not widely used in medical patients. One explanation is that assessing medical patients' risk of VTE is complicated. The risk depends not only on the current illness but also on multiple intrinsic factors, and a variety of strategies for identifying patients who should receive thromboprophylaxis have been suggested. Thromboprophylaxis with unfractionated heparin (UFH) has proved to be effective in reducing the incidence of deep-vein thrombosis and overall mortality in medical patients. Clinical trial evidence, including a meta-analysis, suggests that thromboprophylaxis with low-molecular-weight heparin (LMWH) is at least as effective as with UFH, and also has the advantage of fewer bleeding complications. In particular, two large, randomised clinical trials--Prophylaxis in Medical Patients with Enoxaparin (MEDENOX) and Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients Trial (PREVENT)--showed that thromboprophylaxis with the LMWHs enoxaparin (40 mg s.c. once daily) or dalteparin (5,000 IU once daily) is more effective than placebo and well tolerated in medical patients. In addition, the Thromboembolism-Prevention in Cardiopulmonary Diseases with Enoxaparin (THE-PRINCE) trial showed that enoxaparin treatment was as effective as UFH. These studies provide solid evidence for the widespread use of thromboprophylaxis in medical patients.