3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Dynamic Changes in Arteriovenous Malformations (AVMs): Spontaneous Growth and Resolution of AVM-Associated Aneurysms in Two Pediatric Patients

Arteriovenous malformations (AVMs) of the central nervous system are dynamic lesions that can change with time. One of the most clinically important concerns is the development and potential rupture of AVM-associated aneurysms. In this report, we review pediatric cases of de novo development of AVM-associated aneurysms in 2 children and present the relevant clinical and radiographic records. These 2 cases, coupled with a review of the current literature, offer insight into the risks of AVMs in children and underline the importance of timely treatment of appropriate cases

Prognostic Value of National Comprehensive Cancer Network Lung Cancer Resection Quality Criteria

Background The National Comprehensive Cancer Network (NCCN) surgical resection guidelines for non-small cell lung cancer recommend anatomic resection, negative margins, examination of hilar/intrapulmonary lymph nodes, and examination of three or more mediastinal nodal stations. We examined the survival impact of these criteria. Methods A population-based observational study was done using patient-level data from all curative-intent, non-small cell lung cancer resections from 2004 to 2013 at 11 institutions in four contiguous Dartmouth Hospital referral regions in three US states. We used an adjusted Cox proportional hazards model to assess the overall survival impact of attaining NCCN guidelines. Results Of 2,429 eligible resections, 91% were anatomic, 94% had negative margins, 51% sampled hilar nodes, and 26% examined three or more mediastinal nodal stations. Only 17% of resections met all four criteria; however, there was a significant increasing trend from 2% in 2004 to 39% in 2013 (p \u3c 0.001). Compared with patients whose surgery missed one or more criteria, the hazard ratio for patients whose surgery met all four criteria was 0.71 (95% confidence interval: 0.59 to 0.86, p \u3c 0.001). Margin status and the nodal staging criteria were most strongly linked with survival. Conclusions Attainment of NCCN surgical quality guidelines was low, but improving, over the past decade in this cohort from a high lung cancer mortality region of the United States. The NCCN quality criteria, especially the nodal examination criteria, were strongly associated with survival. The quality of nodal examination should be a focus of quality improvement in non-small cell lung cancer care

Prospective Comparative Effectiveness Trial of Multidisciplinary Lung Cancer Care Within a Community-Based Health Care System

PURPOSE: Multidisciplinary lung cancer care is assumed to improve care delivery by increasing transparency, objectivity, and shared decision making; however, there is a lack of high-level evidence demonstrating its benefits, especially in community-based health care systems. We used implementation and team science principles to establish a colocated multidisciplinary lung cancer clinic in a large community-based health care system and evaluated patient experience and outcomes within and outside this clinic. METHODS: We conducted a prospective frequency-matched comparative effectiveness study (ClinicalTrials.gov identifier: NCT02123797) evaluating the thoroughness of lung cancer staging, receipt of stage-appropriate treatment, and survival between patients receiving care in the multidisciplinary clinic and those receiving usual serial care. Target enrollment was 150 patients on the multidisciplinary arm and 300 on the serial care arm. We frequency-matched patients by clinical stage, performance status, insurance type, race, and age. RESULTS: A total of 526 patients were enrolled: 178 on the multidisciplinary arm and 348 on the serial care arm. After adjusting for other factors, multidisciplinary patients had significantly higher odds (odds ratio [OR]: 2.3 [95% CI, 1.5 to 3.4]) of trimodality staging compared with serial care. Patients on the multidisciplinary arm also had higher odds of receiving invasive stage confirmation (OR: 2.0 [95% CI, 1.4 to 3.1]) and mediastinal stage confirmation (OR: 1.9 [95% CI, 1.3 to 2.8]). Additionally, patients receiving multidisciplinary care were significantly more likely to receive stage-appropriate treatment (OR: 1.8 [95% CI, 1.1 to 3.0]). We found no significant difference in overall or progression-free survival between study arms. CONCLUSION: The multidisciplinary clinic delivered significant improvements in evidence-based quality care on multiple levels. Even in the absence of a demonstrable survival benefit, these findings provide a strong rationale for recommending this model of care

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer

BACKGROUND: Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival. RESEARCH QUESTION: What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival? STUDY DESIGN AND METHODS: We evaluated patients with non-metastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34% in 2014 to 18% in 2019 (P \u3c .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83% vs 66%; P \u3c .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13% received guideline-concordant staging alone; 17% received guideline-concordant treatment alone; and 9% received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95% CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95% CI, 0.37-1.09) compared with neither (P \u3c .0001, log-rank test). INTERPRETATION: Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes