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TP53 aberrations [del(17p) or TP53 mutation] predict poor survival with chemoimmunotherapy in patients with chronic lymphocytic leukaemia (CLL). We evaluated long-term efficacy and safety of first-line ibrutinib-based therapy in patients with CLL bearing TP53 aberrations in a pooled analysis across four studies: PCYC-1122e, RESONATE-2 (PCYC-1115/16), iLLUMINATE (PCYC-1130) and ECOG-ACRIN E1912. The pooled analysis included 89 patients with TP53 aberrations receiving first-line treatment with single-agent ibrutinib (n = 45) or ibrutinib in combination with an anti-CD20 antibody (n = 44). All 89 patients had del(17p) (53% of 89 patients) and/or TP53 mutation (91% of 58 patients with TP53 sequencing results available). With a median follow-up of 49·8 months (range, 0·1-95·9), median progression-free survival was not reached. Progression-free survival rate and overall survival rate estimates at four years were 79% and 88%, respectively. Overall response rate was 93%, including complete response in 39% of patients. No new safety signals were identified in this analysis. Forty-six percent of patients remained on ibrutinib treatment at last follow-up. With median follow-up of four years (up to eight years), results from this large, pooled, multi-study data set suggest promising long-term outcomes of first-line ibrutinib-based therapy in patients with TP53 aberrations. Registered at ClinicalTrials.gov (NCT01500733, NCT01722487, NCT02264574 and NCT02048813)., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To summarise articles reporting on burnout among medical students and residents (trainees) in a narrative review., Methods: MEDLINE was searched for peer-reviewed, English language articles published between 1990 and 2015 reporting on burnout among trainees. The search used combinations of Medical Subject Heading terms medical student, resident, internship and residency, and burnout, professional. Reference lists of articles were reviewed to identify additional studies. A subset of high-quality studies was selected., Results: Studies suggest a high prevalence of burnout among trainees, with levels higher than in the general population. Burnout can undermine trainees' professional development, place patients at risk, and contribute to a variety of personal consequences, including suicidal ideation. Factors within the learning and work environment, rather than individual attributes, are the major drivers of burnout. Limited data are available regarding how to best address trainee burnout, but multi-pronged efforts, with attention to culture, the learning and work environment and individual behaviours, are needed to promote trainees' wellness and to help those in distress., Conclusion: Medical training is a stressful time. Large, prospective studies are needed to identify cause-effect relationships and the best approaches for improving the trainee experience., (© 2015 John Wiley & Sons Ltd.)

Background: There have been few studies on the prevalence of substance use disorders (SUDS) in the physician population at large nor have any studies compared the prevalence of SUDS in American physicians by specialty., Methods: We conducted a national study of SUDS in a large sample of U.S. physicians from all specialty disciplines using the AMA Physician Masterfile. Substance Use Disorders (SUDS) were measured using validated instruments., Results: Of the 27,276 physicians who received an invitation to participate, 7,288 (26.7%) completed surveys. 12.9% of male physicians and 21.4% of female physicians met diagnostic criteria for alcohol abuse or dependence. Abuse of prescription drugs and use of illicit drugs was rare. Factors independently associated with alcohol abuse or dependence were age (OR = .985; p < .0001), hours worked (OR = .994; p = .0094), male gender (OR = .597; p < .0001), being married (OR 1.296; p = .0424) or partnered (OR 1.989; p = .0003), having children (OR .745; p = .0049), and being in any specialty other than internal medicine (OR 1.757; p = .0060). Specialty choice was strongly associated with alcohol abuse or dependence (p = .0011). Alcohol abuse or dependence was associated with burnout (p < .0001), depression (p < .0001), suicidal ideation (p = .0004), lower quality of life (p < .0001), lower career satisfaction (p = .0036), and recent medical errors (p = .0011)., Conclusion: Alcohol abuse or dependence is a significant problem among American physicians. Since prognosis for recovery of physicians from chemical dependency is exceptionally high, organizational approaches for the early identification of problematic alcohol consumption in physicians followed by intervention and treatment where indicated should be strongly supported., (© American Academy of Addiction Psychiatry.)

Objective: To compare the use of liquid-based cytology (LBC) with conventional cytology (CC) in the assessment cervical intraepithelial neoplasia (CIN) prior to colposcopy., Design: Retrospective Cohort Study., Methods: Liquid-based cytology and CC findings were compared with colposcopic assessment and directed cervical biopsy in terms of sensitivity and specificity for high grade lesions only and for any abnormalities. The degree of correlation was sought. Secondary outcomes were unsatisfactory rate and cost., Results: A total of 1961 women had colposcopy of whom 528 had cervical biopsy. LBC and CC have similar sensitivity and specificity for both high-grade lesions and any abnormalities. In comparison with cervical biopsy, LBC and CC sensitivity for high-grade disease was 89.1% and 88.6% respectively and for any abnormalities, the sensitivity was 86.6% and 87.0%. Specificity for high-grade disease was 83.1% and 84.7% and for any abnormalities, the specificity was 53.8% and 56.4%. The unsatisfactory rate was significantly lower in LBC 4.38% compared to 1.84% (P < 0.001). However, the use of LBC was associated with an additional cost of A$1496 for each unsatisfactory smear avoided., Conclusion: In high prevalence setting, LBC showed no statistically significant difference in sensitivity and specificity from CC for the detection of CIN. A reduction in unsatisfactory smears was evident, but at significant additional cost.