Interferon gamma expression and mortality in unselected cohorts of urothelial bladder cancer patients.

BACKGROUND: The role of interferon gamma (IFN-γ) expression in long-term survival has not been studied in patients with urinary bladder cancer (UBC). IFN-γ expression was characterized among various UBC patient cohorts to assess if IFN-γ status is associated with overall survival (OS). METHODS: A tumor-based IFN-γ gene signature was evaluated among adult UBC patients newly diagnosed between 2004 and 2017 from two hospital systems in New York. Patient cohorts included metastatic (stage IV or progressing to stage IV [MBC]), muscle-invasive (stages T2a to T4a [MIBC]), and non-muscle-invasive (carcinoma in situ or stages 0a, 0is, and I [NMIBC]) disease. Descriptive analyses were conducted comparing IFN-γ signature in the highest tertile to those in the lowest two tertiles. RESULTS: 234 patients with bladder cancer were evaluated (56 MBC, 38 MIBC, and 140 NMIBC). Median OS was only reached in the MIBC cohort for those with an IFN-γ signature in the lowest two tertiles (15.03 months [95% CI, 8.50-50.60]). Those with an IFN-γ signature in the highest tertile had a decreased risk of mortality in all cohorts indicating better survival, but this was statistically significant in only the MIBC cohort (adjusted HR = 0.09 [95% CI, 0.01-0.73]). CONCLUSION: IFN-γ signature status was associated with a decreased mortality risk in all cohorts, particularly MIBC, indicating that it may be a prognostic marker of survival in patients with UBC.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

RATIONALE: DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. METHODS: This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. RESULTS: The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p=0.064). CONCLUSION: Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Respiratory syncytial virus surveillance in the United States, 2007-2012: results from a national surveillance system.

BACKGROUND: Annual respiratory syncytial virus (RSV) outbreaks throughout the US exhibit variable patterns in onset, peak month of activity and duration of season. RSVAlert, a US surveillance system, collects and characterizes RSV test data at national, regional, state and local levels. METHODS: RSV test data from 296 to 666 laboratories from 50 states, the District of Columbia and Puerto Rico (as of 2010) were collected during the 2007-2008 to 2011-2012 RSV seasons. Data were collected in early August/September to the following August/September each season. Participating laboratories provided the total number and types of RSV tests performed each week and test results. RSV season onset and offset were defined as the first and last, respectively, of 2 consecutive weeks during which the mean percentage of specimens testing positive for RSV was ≥10%. RESULTS: Nationally, the RSV season onset occurred in October/November of each year with offset occurring in March/April of the following year. The RSV season averaged 20 weeks and typically occurred earliest in the South and latest in the West. The onset, offset and duration varied considerably within the U.S. Department of Health and Human Services regions. RSV activity in Puerto Rico was elevated throughout the 2-year period studied. Median onset in core-based statistical areas ranged from 2 weeks earlier to 5 weeks later than those in their corresponding states. CONCLUSIONS: Substantial variability existed in the timing of RSV activity at all geographic strata analyzed. RSV actively circulated (ie, ≥10%) in many areas outside the traditionally defined RSV epidemic period of November to March.

Laboratory testing trends for respiratory syncytial virus, 2007-2011.

BACKGROUND: Antigen detection tests have been the most common diagnostic assay used to detect and diagnose respiratory syncytial virus (RSV). The utility and increased sensitivity of polymerase chain reaction (PCR) tests have been reported; however, their use in US hospital laboratories is not well characterized. OBJECTIVE: To describe changes in RSV test types used by US hospital-affiliated laboratories, focusing on PCR testing prevalence. STUDY DESIGN: Data were collected from 480 to 666 laboratories each RSV season (2007-2008 through 2010-2011) across 50 states, the District of Columbia, and Puerto Rico. A descriptive analysis was conducted using this convenience sample of RSV tests conducted from November to April each season. Total numbers and types of RSV tests performed were reported weekly and weekly proportions by test type were calculated. Kendall τ rank correlation was used to quantify associations between time and proportions of each test type. RESULTS: PCR tests accounted for 2%, 3%, 16%, and 21% of weekly tests (total range, 381,068-481,654 over 4 seasons) conducted each season from 2007 to 2011, respectively. The proportion of laboratories reporting ≥1 PCR tests was 4%, 5%, 10%, and 16%, respectively. Decreases in antigen testing and viral culture were similarly observed. CONCLUSIONS: Although antigen detection was the predominant test type reported in the sample of US hospital laboratories for RSV testing, PCR use increased to >20% of tests reported. These results demonstrate the increasing contribution of PCR to RSV surveillance. RSV surveillance systems relying solely on antigen detection results will not capture an increasing proportion of RSV test results.

Muscle-power quality: does sex or race affect movement velocity in older adults?

To determine sex and race differences in muscle power per unit of muscle contraction, knee-extensor muscle power normalized for knee-extensor muscle volume was measured in 79 middle-aged and older adults (30 men and 49 women, age range 50-85 years). Results revealed that women displayed a 38% faster peak movement velocity than men and African Americans had a 14% lower peak movement velocity than Whites of a similar age when expressed per unit of involved muscle (p < .001). As expected, men exhibited greater knee-extensor strength and peak power per unit of muscle than women, but women had a faster knee- extension movement velocity per unit of muscle than men at the same relative strength level. Moreover, African Americans had greater knee-extensor muscle volume than Whites but exhibited lower knee-extensor strength and lower movement velocity per unit of muscle when tested at the same relative strength levels.

Effects of moderate-velocity strength training on peak muscle power and movement velocity: do women respond differently than men?

The effects of a 10-wk unilateral knee extension strength training (ST) program on peak power (PP) and peak movement velocity (PV), at given absolute (force load) and relative (same % of 1 repetition maximum) resistances (loads), were examined in 30 older men [64 yr (7 SD)] and 32 older women [62 yr (6 SD)]. PP increased significantly in both men and women at the same absolute (P < 0.001) and relative loads (P < 0.01) with ST. Men had a significantly greater increase in relative PP than women with ST at 60% (P < 0.01) and 70% (P < 0.001) of 1 repetition maximum when covarying for baseline differences and age. However, when each subject was tested at the same absolute load and when PP was normalized for the muscle volume of the trained knee extensors (i.e., absolute muscle power quality), women increased by 9% (P < 0.05), whereas men did not change. Both men and women increased their absolute PV (P < 0.001) but decreased their relative PV significantly with ST (P < 0.05). However, when baseline values and age were covaried, women had significantly less of a decrease in relative PV quality with ST than men (P < 0.01), although the difference was small. These normalized data suggest that ST-induced increases in PP depend on muscular hypertrophy in men, but not in women, providing further support for the hypothesis developed from our previous report (Ivey FM, Tracy BL, Lemmer JT, NessAiver M, Metter EJ, Fozard JL and Hurley BF. J Gerontol A Biol Sci Med Sci 55: B152-B157, 2000) that improvements in muscle function with ST result from nonmuscle mass adaptations to a greater extent in women than men.

Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training.

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50-81 years old) were studied before and after approximately 5-6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P = 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT.