Value of a small control group for estimating intervention effectiveness: results from simulations of immunization effectiveness studies

To improve evidence for public health practice, the conduct of effectiveness studies by practitioners is needed and may be stimulated if knowledge that smaller than usual samples may provide the same reliability of intervention effect size as larger samples

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology

Serving as Trusted Messengers about COVID-19 Vaccines and Therapeutics

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic

Vaccination differences among U.S. adults by their self-identified sexual orientation, National Health Interview Survey, 2013-2015.

IntroductionVery few studies have explored the associations between self-identified sexual orientation and comprehensive vaccination coverage. Most of the previous studies that reported health disparities among lesbian, gay and bisexual populations were not based on a nationally representative sample of U.S. adults, limiting the generalizability of the findings. Starting in 2013, the National Health Interview Survey (NHIS) included questions to ascertain the adult's self-identified sexual orientation that allowed national level vaccination estimation by sexual orientation. This study examined associations of self-reported vaccination coverage for selected vaccines among U.S. adults by their sexual orientation.MethodsWe analyzed combined data from 2013-2015 NHIS, a nationally representative probability-based health survey of the noninstitutionalized U.S. population ≥18 years. For vaccines other than influenza, weighted proportions were calculated. Influenza coverage was calculated using the Kaplan-Meier procedure. Multivariable logistic regression models were used to calculate adjusted prevalence differences for each vaccine overall and stratified by sexual orientation and to identify factors independently associated with vaccination.ResultsSignificant differences were observed by sexual orientation for self-reported receipt of human papillomavirus (HPV), hepatitis A (HepA), hepatitis B (HepB), and influenza vaccination. Bisexual females (51.6%) had higher HPV coverage than heterosexual females (40.2%). Gay males (40.3% and 53.6%, respectively) had higher HepA and HepB coverage than heterosexual males (25.4% and 32.6%, respectively). Bisexual females (33.9% and 58.5%, respectively) had higher HepA and HepB coverage than heterosexual females (23.5% and 38.4%, respectively) and higher HepB coverage than lesbian females (45.4%). Bisexual adults (34.1%) had lower influenza coverage than gay/lesbian (48.5%) and heterosexual adults (43.8%). Except for the association of having self-identified as gay/lesbian orientation with greater likelihood of HepA, HepB, and influenza vaccination, sexual orientation was not associated with higher or lower likelihood of vaccination. Health status or other behavioral characteristics studied had no consistent relationship with vaccination among all populations.ConclusionDifferences were identified in vaccination coverage among the U.S. adult population by self-reported sexual orientation. This study is the first to assess associations of sexual orientation with a comprehensive list of vaccinations. Findings from this study can serve as a baseline for monitoring changes over time. All populations could benefit from improved vaccination

Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report

We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1, 31%), and frail (score ≥2, 30%). The 3-year overall survival was 84% in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. The cumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2% in fit, 26.4% in intermediate-fitness (HR, 1.23; P = .217), and 34.0% in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12 months was 16.5% in fit, 20.8% in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506)