Pirtobrutinib: A New and Distinctive Treatment Option for B-Cell Malignancies.

OBJECTIVE: The objective was to evaluate the efficacy/safety of pirtobrutinib in the treatment of B-cell malignancies and distinguish it from other available Bruton's tyrosine kinase (BTK) inhibitors. DATA SOURCES: A literature search of PubMed (January 2021 through November 2023) and Clinicaltrials.gov was conducted using terms pirtobrutinib, Jaypirca, and LOXO 305. Licensing trials of available BTK inhibitors were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language clinical trials were evaluated. DATA SYNTHESIS: Pirtobrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) based largely on a phase 1/2 study in B-cell malignancies. Pirtobrutinib demonstrated a 73% overall response rate (ORR) in the CLL population and 58% in MCL. Pirtobrutinib has activity in patients resistant to earlier-generation, covalent BTK inhibitors. In fact, the ORRs were similar in BTK-pretreated and naïve patients. Adverse effects include fatigue, diarrhea, bleeding, and infection. Atrial fibrillation, a class effect of BTK inhibitors, may be less common with pirtobrutinib. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Compared with earlier-generation BTK inhibitors, pirtobrutinib is more selective for BTK and binds noncovalently to the receptor. Ongoing studies are evaluating pirtobrutinib's use in multiple B-cell malignancies and comparing it with other BTK inhibitors. CONCLUSION: The characteristics of pirtobrutinib render it useful in the treatment of B-cell malignancies no longer responding to a previous BTK inhibitor, and results from ongoing clinical trials may support future expanded use.

Venous Thromboembolism Prophylaxis Compliance before and after Electronic Health Record Implementation.

Background: Adherence to American College of Chest Physicians (CHEST) and National Comprehensive Cancer Network (NCCN) guidelines for venous thromboembolism (VTE) prophylaxis helps avoid thromboembolic complications during hospitalization. Electronic health records (EHR) have the potential to make an impact on guideline adherence, but data are lacking. Objectives: To determine compliance with VTE prophylaxis guidelines in internal medicine and oncology populations and to determine whether EHR implementation had any effect on the rate and appropriateness of prophylaxis practices. Methods: A retrospective chart review was conducted on medical and oncology patients admitted to the hospital for a 2-month period pre-EHR and post-EHR implementation. Risk assessment tools were available pre and post, however they were not mandatory. The rate of VTE prophylaxis was compared between the 2 time periods, with appropriateness assessed in a subgroup of participants without prophylaxis. Results: A total of 2,423 patients on the oncology and internal medicine floors were identified during the pre-EHR (n = 1,171) and post-EHR (n = 1,252) time periods. Patients in the post-EHR group were less likely to be prescribed prophylaxis as compared to those in the pre-EHR group (43% vs 50%; P = .001). In the patients audited for proper prophylaxis use (n = 750), significantly more patients in the post-EHR group had risk factors (84% vs 53%; P <.001) and contraindications (23% vs 8%; P = .001) than in the pre-EHR group. Noncompliance to prophylaxis in patients who were candidates (positive risk factors without contraindications) occurred more often in the post-EHR group (51% vs 39%; P <.001). Conclusion: Implementation of an EHR was associated with an increase in the documentation of risk factors and contraindications; however, there was a significant decrease in VTE prophylaxis utilization after EHR implementation.

What's New in Dementia Risk Prediction Modelling? An Updated Systematic Review.

Introduction: Identifying individuals at high risk of dementia is critical to optimized clinical care, formulating effective preventative strategies, and determining eligibility for clinical trials. Since our previous systematic reviews in 2010 and 2015, there has been a surge in dementia risk prediction modelling. The aim of this study was to update our previous reviews to explore, and critically review, new developments in dementia risk modelling. Methods: MEDLINE, Embase, Scopus, and Web of Science were searched from March 2014 to June 2022. Studies were included if they were population- or community-based cohorts (including electronic health record data), had developed a model for predicting late-life incident dementia, and included model performance indices such as discrimination, calibration, or external validation. Results: In total, 9,209 articles were identified from the electronic search, of which 74 met the inclusion criteria. We found a substantial increase in the number of new models published from 2014 (>50 new models), including an increase in the number of models developed using machine learning. Over 450 unique predictor (component) variables have been tested. Nineteen studies (26%) undertook external validation of newly developed or existing models, with mixed results. For the first time, models have also been developed in low- and middle-income countries (LMICs) and others validated in racial and ethnic minority groups. Conclusion: The literature on dementia risk prediction modelling is rapidly evolving with new analytical developments and testing in LMICs. However, it is still challenging to make recommendations about which one model is the most suitable for routine use in a clinical setting. There is an urgent need to develop a suitable, robust, validated risk prediction model in the general population that can be widely implemented in clinical practice to improve dementia prevention.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.