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Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30–0.59; P  < 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30–0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 . In this pre-specified interim analysis, patients with resected stage IIB/C melanoma who received adjuvant nivolumab had significantly prolonged recurrence-free survival compared to placebo-treated patients, providing another treatment option for this population.

Research into mechanisms of skin scarring identified transforming growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFβ3). In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0·25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00847925, NCT00847795, and NCT00629811. In two studies, avotermin 50 ng/100 μL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14; p=0·001) at month 6 and 8 mm (−29 to 18; p=0·0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14·84 mm [95 % CI 5·5–24·2] at 5 ng/100 μL per linear cm to 64·25 mm [49·4–79·1] at 500 ng/100 μL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less abnormal orientation of collagen fibres in the reticular dermis versus five [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16·12 mm (95% CI 10·61–21·63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing. Avotermin has potential to provide an accelerated and permanent improvement in scarring. Renovo (UK).

Recent reports have suggested that internet search behaviour may be a valuable tool to estimate melanoma incidence and mortality. Previous studies have used incorrect statistical methods, were focussed on the United States and/or did not use non-cancer control search terms to provide a context for interpreting the effects seen with the cancer-related terms. Using more robust statistical methods we found that no cancer search terms were significantly, or strongly correlated with melanoma incidence in 6 countries.

Combination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial. This open-label, multicentre, phase 2 study (CheckMate 204) included adults (aged ≥18 years) with measurable MBM (0·5–3·0 cm in diameter). Asymptomatic patients (cohort A) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and no neurological symptoms or baseline corticosteroid use; symptomatic patients (cohort B) had an ECOG performance status of 0–2 with stable neurological symptoms and could be receiving low-dose dexamethasone. Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg was given intravenously every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks for up to 2 years, until disease progression or unacceptable toxicity. The primary endpoint was intracranial clinical benefit rate (complete responses, partial responses, or stable disease lasting ≥6 months) assessed in all treated patients. Intracranial progression-free survival and overall survival were key secondary endpoints. This study is registered with ClinicalTrials.gov, NCT02320058. Between Feb 19, 2015, and Nov 1, 2017, 119 (72%) of 165 screened patients were enrolled and treated: 101 patients were asymptomatic (cohort A; median follow-up 34·3 months [IQR 14·7–36·4]) and 18 were symptomatic (cohort B; median follow-up 7·5 months [1·2–35·2]). Investigator-assessed intracranial clinical benefit was observed in 58 (57·4% [95% CI 47·2–67·2]) of 101 patients in cohort A and three (16·7% [3·6–41·4]) of 18 patients in cohort B; investigator-assessed objective response was observed in 54 (53·5% [43·3–63·5]) patients in cohort A and three (16·7% [3·6–41·4]) patients in cohort B. 33 (33%) patients in cohort A and three (17%) patients in cohort B had an investigator-assessed intracranial complete response. For patients in cohort A, 36-month intracranial progression-free survival was 54·1% (95% CI 42·7–64·1) and overall survival was 71·9% (61·8–79·8). For patients in cohort B, 36-month intracranial progression-free survival was 18·9% (95% CI 4·6–40·5) and overall survival was 36·6% (14·0–59·8). The most common grade 3–4 treatment-related adverse events (TRAEs) were increased alanine aminotransferase and aspartate aminotransferase (15 [15%] of 101 patients each) in cohort A; no grade 3 TRAEs occurred in more than one patient each in cohort B, and no grade 4 events occurred. The most common serious TRAEs were colitis, diarrhoea, hypophysitis, and increased alanine aminotransferase (five [5%] of each among the 101 patients in cohort A); no serious TRAE occurred in more than one patient each in cohort B. There was one treatment-related death (myocarditis in cohort A). The durable 3-year response, overall survival, and progression-free survival rates for asymptomatic patients support first-line use of nivolumab plus ipilimumab. Symptomatic disease in patients with MBM remains difficult to treat, but some patients achieve a long-term response with the combination. Bristol Myers Squibb.

INTRODUCTIONMortality and morbidity (M&M) meetings present a forum to discuss and review in-hospital deaths and complications to improve patient care. However, it remains an untapped resource to improve the exposure of the trainees to the principles of patient safety METHODSWe modified the departmental M&M meetings to enhance the delivery of patient safety education. The meeting started with a 5-minute overview of general patient safety principles, followed by a trainee-led discussion of a recent patient safety incident where opinions were sought about key learning points and ways to prevent the incident from happening in future. The discussion concluded with a patient safety presentation summarizing the salient points that were mapped to the WHO Patient Safety Curriculum. The suggestions from the meeting were noted, and the changes were instituted in the department over the next month and were reported back in the next meeting. RESULTSFrom January to August 2012, seven enhanced M&M meetings were organized and attended by orthopaedic specialty trainees in a postgraduate Deanery. We explored the early impact of these monthly discussions by using the Junior Doctors’ Patient Safety Attitudes and Climate Questionnaire as an assessment tool. The questionnaire reports an early impact on patient safety knowledge, awareness, and attitudes to patient safety; however, more work is needed to improve the workplace safety climate. CONCLUSIONSWe recommend immediate introduction of the enhanced M&M meetings focusing on patient safety in the other disciplines and postgraduate deaneries.

Introduction Engagement of junior doctors in patient safety initiatives is high on the national agenda, but there is a lack of studies evaluating patient safety attitudes among junior doctors. Methods The Junior Doctor–Patient Safety Attitudes and Climate Questionnaire is a multidimensional scale created using items from already-validated scales and inclusion of new items based on further review. It consists of three subscales: ‘knowledge and training’ (10 items), ‘attitudes to patient safety’ (15 items) and ‘perception of workplace safety climate’ (15 items). This was disseminated to foundation trainees, general practice trainees and hospital core and speciality trainees via the Deanery distribution lists and responses were collected anonymously. Results A total of 527 complete responses were collected; although self-declared knowledge in patient safety concepts was high, there was less declared understanding of a ‘high reliability organisation’ (74% no/unsure) and the concept of active failures/latent conditions (60% no/unsure). The greatest agreement was demonstrated for the statement ‘Even the most experienced and competent doctors make errors’ (p<0.01). However, more senior trainees and surgical trainees (vs medical trainees) demonstrated greater agreement with ‘Medical error is a sign of incompetence’ (p<0.01). More junior trainees demonstrated greater agreement with ‘Management is more interested in meeting performance targets than focusing on patient safety issues’ (p<0.01). Conclusions This study demonstrates subtle differences in attitudes to patient safety among junior doctors of different grades and specialities. These should be taken into account when designing interventions to improve patient safety education and culture among junior doctors.

Background It is becoming more and more accepted that better aesthetic results can be obtained when the lower eyelid is considered as part of the midface when contemplating surgical rejuvenation. Descent of the orbicularis muscle and midface tissue causes malar bags, loss of volume over the tear-trough, apparent vertical lengthening of the lower eyelid, and an accentuation of the orbit-cheek junction. Methods We describe a triple-layer technique that effectively corrects these problems, performed under local anesthesia and via a standard subciliary incision, to separately reposition the postseptal fat, suborbicularis oculi fat, and the musculocutaneous layer of skin and orbicularis oculi. We present a detailed analysis of the complications arising from a series of over 500 patients, in which this technique has been performed by the senior author. Results The average patient age at the time of surgery was 51 years old (±7.9), with a median follow-up of 7 months (range 3–121). Complications were observed in 77 of 512 cases. In total, 44 of these cases required surgical reintervention under local anesthesia (rated as major complications and all reinterventions lasted <30 min) and 33 cases were treated conservatively (minor complications). Conclusion The triple-layer midface lift is an effective way to reverse the combination of ptosis and changes in volume of the aging midface. It yields long-lasting results with a minimal risk for complications, particularly when a tarsal tuck is performed simultaneously in patients at high risk for the development of scleral show. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .