Concept: Normal distribution
Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. Methods In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. Results The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. Conclusions Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 8 years ago
“Climate dice,” describing the chance of unusually warm or cool seasons, have become more and more “loaded” in the past 30 y, coincident with rapid global warming. The distribution of seasonal mean temperature anomalies has shifted toward higher temperatures and the range of anomalies has increased. An important change is the emergence of a category of summertime extremely hot outliers, more than three standard deviations (3σ) warmer than the climatology of the 1951-1980 base period. This hot extreme, which covered much less than 1% of Earth’s surface during the base period, now typically covers about 10% of the land area. It follows that we can state, with a high degree of confidence, that extreme anomalies such as those in Texas and Oklahoma in 2011 and Moscow in 2010 were a consequence of global warming because their likelihood in the absence of global warming was exceedingly small. We discuss practical implications of this substantial, growing, climate change.
Using mixed design analysis of variance (ANOVA), this paper investigates the effects of a subtle simulated increase in adiposity on women’s employment chances in the service sector. Employing a unique simulation of altering individuals' BMIs and the literature on “aesthetic labour”, the study suggests that, especially for women, being heavier, but still within a healthy BMI, deleteriously impacts on hireability ratings. The paper explores the gendered dimension of this prejudice by asking whether female employees at the upper end of a healthy BMI range are likely to be viewed more negatively than their overtly overweight male counterparts. The paper concludes by considering the implications of these findings.
Background In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. Methods We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. Results A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. Conclusions In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649 .).
Objective To determine if a simple stimulation method increases the rate of infant voiding for clean catch urine within five minutes.Design Randomised controlled trial.Setting Emergency department of a tertiary paediatric hospital, Australia.Participants 354 infants (aged 1-12 months) requiring urine sample collection as determined by the treating clinician. 10 infants were subsequently excluded.Interventions Infants were randomised to either gentle suprapubic cutaneous stimulation (n=174) using gauze soaked in cold fluid (the Quick-Wee method) or standard clean catch urine with no additional stimulation (n=170), for five minutes.Main outcome measures The primary outcome was voiding of urine within five minutes. Secondary outcomes were successful collection of a urine sample, contamination rate, and parental and clinician satisfaction with the method.Results The Quick-Wee method resulted in a significantly higher rate of voiding within five minutes compared with standard clean catch urine (31% v 12%, P<0.001), difference in proportions 19% favouring Quick-Wee (95% confidence interval for difference 11% to 28%). Quick-Wee had a higher rate of successful urine sample collection (30% v 9%, P<0.001) and greater parental and clinician satisfaction (median 2 v 3 on a 5 point Likert scale, P<0.001). The difference in contamination between Quick-Wee and standard clean catch urine was not significant (27% v 45%, P=0.29). The number needed to treat was 4.7 (95% confidence interval 3.4 to 7.7) to successfully collect one additional urine sample within five minutes using Quick-Wee compared with standard clean catch urine.Conclusions Quick-Wee is a simple cutaneous stimulation method that significantly increases the five minute voiding and success rate of clean catch urine collection.Trial registration Australian New Zealand Clinical Trials Registry ACTRN12615000754549.
Moderate-intensity exercise has attracted considerable attention because of its safety and many health benefits. Tai Chi, a form of mind-body exercise that originated in ancient China, has been gaining popularity. Practicing Tai Chi may improve overall health and well-being; however, to our knowledge, no study has evaluated its relationship with mortality. We assessed the associations of regular exercise and specifically participation in Tai Chi, walking, and jogging with total and cause-specific mortality among 61,477 Chinese men in the Shanghai Men’s Health Study (2002-2009). Information on exercise habits was obtained at baseline using a validated physical activity questionnaire. Deaths were ascertained through biennial home visits and linkage with a vital statistics registry. During a mean follow-up of 5.48 years, 2,421 deaths were identified. After adjustment for potential confounders, men who exercised regularly had a hazard ratio for total mortality of 0.80 (95% confidence interval: 0.74, 0.87) compared with men who did not exercise. The corresponding hazard ratios were 0.80 (95% confidence interval: 0.72, 0.89) for practicing Tai Chi, 0.77 (95% confidence interval: 0.69, 0.86) for walking, and 0.73 (95% confidence interval: 0.59, 0.90) for jogging. Similar inverse associations were also found for cancer and cardiovascular mortality. The present study provides the first evidence that, like walking and jogging, practicing Tai Chi is associated with reduced mortality.
Background In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. Methods We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient’s ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m(2) of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m(2) were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. Results The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m(2) (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m(2) (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m(2); 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. Conclusions Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .).
Background Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. Methods A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. Results The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). Conclusions Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784 .).
To identify student- and school-level sociodemographic characteristics associated with overweight and obesity, the authors conducted cross-sectional analyses of data from 624,204 public school children (kindergarten through 12th grade) who took part in the 2007-2008 New York City Fitnessgram Program. The overall prevalence of obesity was 20.3%, and the prevalence of overweight was 17.6%. In multivariate models, the odds of being obese as compared with normal weight were higher for boys versus girls (odds ratio (OR) = 1.39, 95% confidence interval (CI): 1.36, 1.42), for black (OR = 1.11, 95% CI: 1.07, 1.15) and Hispanic (OR = 1.48, 95% CI: 1.43, 1.53) children as compared with white children, for children receiving reduced-price (OR = 1.17, 95% CI: 1.13, 1.21) or free (OR = 1.12, 95% CI: 1.09, 1.15) school lunches as compared with those paying full price, and for US-born students (OR = 1.54, 95% CI: 1.50, 1.58) as compared with foreign-born students. After adjustment for individual-level factors, obesity was associated with the percentage of students who were US-born (across interquartile range (75th percentile vs. 25th), OR = 1.10, 95% CI: 1.07, 1.14) and the percentage of students who received free or reduced-price lunches (across interquartile range, OR = 1.13, 95% CI: 1.10, 1.18). The authors conclude that individual sociodemographic characteristics and school-level sociodemographic composition are associated with obesity among New York City public school students.
- The international journal of behavioral nutrition and physical activity
- Published over 8 years ago
BACKGROUND: Slow eating has been associated with enhanced satiation, but also with increased water intake. Therefore, the role of water ingestion in regard to eating rate needs to be discerned. This study examined the influence of eating rate on appetite regulation and energy intake when water intake is controlled. METHODS: In a randomized design, slow and fast eating rates were compared on two occasions, in 30 women (22.7+/-1.2y; BMI=22.4+/-0.4kg/m2) who consumed an ad libitum mixed-macronutrient lunch with water (300 mL). Satiation was examined as the main outcome by measuring energy intake during meals. At designated times, subjects rated hunger, satiety, desire-to-eat, thirst, and meal palatability on visual analogue scales. Paired t-tests were used to compare hypothesis-driven outcomes. Appetite ratings were compared across time points and conditions by repeated measures analysis of variance (ANOVA) using a within-subject model. RESULTS: Energy intake and appetite ratings did not differ between conditions at meal completion. However, subjects rated less hunger and tended to rate lower desire-to-eat and greater satiety at 1 hour following the slow condition. CONCLUSIONS: Results tend to support a role of slow eating on decreased hunger and higher inter-meal satiety when water intake is controlled. However, the lack of significant differences in energy intake under these conditions indicates that water intake may account for the effects of eating rate on appetite regulation.