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JAMA Network Open Aug 2019Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized.
OBJECTIVE
To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy.
DATA SOURCES
PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018.
STUDY SELECTION
Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected.
DATA EXTRACTION AND SYNTHESIS
Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs.
MAIN OUTCOMES AND MEASURES
The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded.
RESULTS
Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02).
CONCLUSIONS AND RELEVANCE
Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.
Topics: Acrylonitrile; Adult; Aged; Aged, 80 and over; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Female; Humans; Male; Melanoma; Middle Aged; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Skin Neoplasms; Young Adult
PubMed: 31397860
DOI: 10.1001/jamanetworkopen.2019.8890 -
Applied Ergonomics Nov 2021Additive Manufacturing (AM) facilitates product personalization and iterative design, which makes it an ideal technology for ergonomic product development. In this... (Review)
Review
Additive Manufacturing (AM) facilitates product personalization and iterative design, which makes it an ideal technology for ergonomic product development. In this study, a systematic review was conducted of the literature regarding the use of AM in ergonomic-product design, and methodological aspects of the studies were analyzed. A literature search was performed using the keywords "3D print*," "additive manufacturing," "ergonomic*" and "human factors". Included were studies reporting the use of AM specifically in ergonomic design of products/prototypes including the detailing of an ergonomic testing methodology used for evaluation. Forty studies were identified pertaining to the fields of medicine, assistive technology, wearable technology, hand tools, testing devices and others. The most commonly used technology was fused deposition modeling with polylactic acid, but the overall preferred material was acrylonitrile butadiene styrene. Various combinations of objective/subjective and qualitative/quantitative product evaluation methods were used. Based on the findings, recommendations were developed to facilitate the choice of most suitable AM technologies and materials for specific applications in ergonomics.
Topics: Ergonomics; Humans; Printing, Three-Dimensional; Technology
PubMed: 34256321
DOI: 10.1016/j.apergo.2021.103528