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The short physical performance battery and incident heart failure among older women: the OPACH study

Am J Prev Cardiol

2021 Chongzhi Di

Objective: Reduced functional capacity is a hallmark of early pre-clinical stages of heart failure (HF). The Short Physical Performance Battery (SPPB) is a valid measure of lower extremity physical function, has relatively low implementation burden, and is associated with cardiovascular disease and mortality. However, the SPPB-HF association is understudied in older women among whom HF burden is high. Methods: Women (n=5325; mean age 797 years; 34% Black, 18% Hispanic, and 49% White) without prior HF completed the SPPB consisting of standing balance, strength, and walking tests that were summarized as a composite score from 0 (lowest) to 12 (highest), categorized as very low (0-3), low (4-6), medium (7-9), or high (10-12). Participants were followed for up to 8 years for incident HF (306 cases identified). Cox proportional hazards regression estimated hazard ratios (HR) adjusting for age, race/ethnicity, education, smoking, alcohol, diabetes, hypertension, COPD, osteoarthritis, depression, BMI, systolic blood pressure, lipids, glucose, and accelerometer-measured moderate-vigorous physical activity (MVPA) and sedentary time. Results: Incident HF cases (crude rate per 1000 person-years) in the four SPPB categories (very low to high) were 34 (26.0), 79 (14.5), 128 (9.3), and 65 (5.6). Corresponding multivariable-adjusted HRs (95% CIs) were 2.22 (1.34-3.66), 1.63 (1.11-2.38), 1.39 (1.00-1.94), and 1.00 (referent; P-trend<0.001). Higher HF risk was associated with lower SPPB in women with major modifiable HF risk factors including obesity (HR per 3-unit SPPB decrement: present HR=1.41, absent HR=1.41), hypertension (present HR=1.45, absent HR=1.30), diabetes (present HR=1.32, absent HR=1.44), and lower accelerometer-measured MVPA (<45 min/day HR=1.29, 45min/day HR=1.60); all P-interaction>0.10. Conclusion: Lower SPPB scores were associated with greater risk of incident HF in older women even after accounting for differences in HF risk factors and objectively measured PA. Implementing the SPPB in clinical settings could potentially enhance individual-level HF risk assessment, which should be further explored.

The Inventory of Physical Activity Barriers for Adults 50 Years and Older: Refinement and Validation


2021 Salene Jones

BACKGROUND AND OBJECTIVES: Due to health consequences associated with insufficient physical activity (PA), particularly among aging adults, healthcare providers should assess and address lack of PA participation. Addressing lack of PA means developing individualized PA prescriptions that incorporate solutions to PA participation barriers. Assessing PA participation barriers can be done through the Social-Ecological Model-based Inventory of Physical Activity Barriers Scale (IPAB). This study aimed to refine the initial 40-item IPAB and determine its reliability and validity. RESEARCH DESIGN AND METHODS: Five hundred and three community-dwelling adults 50 years and older completed a demographic and health questionnaire, the Physical Activity Vital Sign, the IPAB, and a feedback questionnaire. For scale refinement, half of the data was used for exploratory factor analysis and the other half for confirmatory factor analysis. The refined scale underwent reliability and validity assessment, including internal consistency, test-retest reliability, and construct validity. RESULTS: The refined scale contains 27 items consisting of seven factors and one stand-alone item: 1) Environmental, 2) Physical Health, 3) PA-Related Motivation, 4) Emotional Health, 5) Time, 6) Skills, 7) Social, and 8) Energy (a stand-alone item). The 27-item IPAB has good internal consistency (alpha= 0.91) and high test-retest reliability (ICC= 0.99). The IPAB's mean scores were statistically different between those who met the recommended levels of PA and those who did not (p < 0.001). DISCUSSION AND IMPLICATIONS: The information gathered through the IPAB can guide discussions related to PA participation barriers and develop individualized PA prescriptions that incorporate solutions to the identified barriers.

High pre-diagnosis inflammation-related risk score associated with decreased ovarian cancer survival

Cancer Epidemiol Biomarkers Prev

2021 Holly Harris; Mary Anne Rossing

Background There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. Methods This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. Pre-diagnosis inflammatory-related exposures of interest included alcohol use, aspirin use, other nonsteroidal anti-inflammatory drug use, body mass index, environmental tobacco smoke exposure, history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis, menopausal hormone therapy use, physical inactivity, smoking status, and talc use. Using Cox proportional hazards (PH) models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed and its association with survival was assessed using Cox PH models in the remaining 50% of the data. Results There was a statistically significant trend of increasing risk of death per quartile of the IRRS (HR=1.09, 95% CI 1.03-1.14). Women in the upper quartile of the IRRS had 31% higher death rate compared to the lowest quartile (95% CI 1.11-1.54). Conclusions A higher pre-diagnosis IRRS was associated with increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether post-diagnosis exposures are also associated with survival. Impact Given that pre- and post-diagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among ovarian cancer patients.

Advancing diversity: the role of international medical graduates

Lancet Gastroenterol Hepatol

2021 Rachel Issaka


Full title: A large-scale transcriptome-wide association study (TWAS) of 10 blood cell phenotypes reveals complexities of TWAS fine-mapping

Genet Epidemiol

2021 Alex Reiner; Stephanie Bien; Charles Kooperberg

Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort. We found 239 significant gene-trait associations with hematological measures; we replicated 71 associations at pā€‰<ā€‰0.05 in a TWAS meta-analysis consisting of up to 35,900 Europeans from the Women's Health Initiative, Atherosclerosis Risk in Communities Study, and BioMe Biobank. Additionally, we attempted to refine this list of candidate genes by performing conditional analyses, adjusting for individual variants previously associated with hematological measures, and performed further fine-mapping of TWAS loci. To facilitate interpretation of our findings, we designed an R Shiny application to interactively visualize our TWAS results by integrating them with additional genetic data sources (GWAS, TWAS from multiple reference panels, conditional analyses, known GWAS variants, etc.). Our results and application highlight frequently overlooked TWAS challenges and illustrate the complexity of TWAS fine-mapping.

A genome-wide search for determinants of survival in 1926 patients with advanced colorectal cancer with follow-up in over 22,000 patients

Eur J Cancer

2021 Ulrike Peters; Amanda Phipps; Yi Lin; Polly Newcomb

BACKGROUND: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. PATIENTS AND METHODS: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P<1.010-5), we conducted sensitivity analyses based on the time from diagnosis to death and sought independent replications in 5675 patients from the Study of Colorectal Cancer in Scotland (SOCCS) and 16,964 patients from the International Survival Analysis in Colorectal cancer Consortium (ISACC). We analysed the Human Protein Atlas to determine if ERBB4 expression was associated with survival in 438 patients with colon adenocarcinomas. RESULTS: The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR]=1.24, 95% confidence interval [CI]=1.16-1.32, P=1.910-7). SNPs at 17 loci had suggestive associations for OS and all had similar effects on the time from diagnosis to death. No lead SNPs were independently replicated in the meta-analysis of all patients from SOCCS and ISACC. However, rs79612564 was significant in stage-IV patients from SOCCS (P=2.110-2) but not ISACC (P=0.89)and SOCCS combined with COIN and COIN-B attained genome-wide significance (P=1.710-8). Patients with high ERBB4 expression in their colon adenocarcinomas had worse survival (HR=1.50, 95% CI=1.1-1.9, P=4.610-2). CONCLUSIONS: Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.

Bone changes with candidate PrEP regimens containing tenofovir disoproxil fumarate and/or maraviroc and/or emtricitabine in US men and women: HPTN 069/ACTG A5305

J Antimicrob Chemother

2021 Ying Chen; Krista Yuhas

BACKGROUND: Tenofovir disoproxil fumarate-containing pre-exposure prophylaxis (PrEP) has been associated with decreases in bone mineral density (BMD), but the bone effects of other non-tenofovir disoproxil fumarate candidate PrEP regimens are not well described. METHODS: The HPTN 069/ACTG A5305 study randomized 406 US cisgender men and transgender women, and 188 cisgender women at risk for HIV infection to one of four double-blinded regimens: (i) maraviroc; (ii) maraviroc + emtricitabine; (iii) maraviroc + tenofovir disoproxil fumarate; or (iv) tenofovir disoproxil fumarate + emtricitabine. BMD was measured in a subset of participants at the lumbar spine (LS) and hip by dual-energy X-ray absorptiometry (DXA) at baseline and 48 weeks. Percentage change in LS and hip BMD was compared between the tenofovir disoproxil fumarate- and non-tenofovir disoproxil fumarate-containing arms by Wilcoxon rank-sum tests and multiple linear regression adjusting for sex, race and baseline BMI. RESULTS: At baseline (n = 307), the median age was 33 years, 56% male and 43% black. At the hip, the median percentage change in BMD at 48 weeks was -1.05% in the tenofovir disoproxil fumarate arms and 0.0% in the non-tenofovir disoproxil fumarate arms (between group P = 0.001). No interaction by sex was observed. The median percentage change in LS BMD was not different between arms. CONCLUSIONS: Tenofovir disoproxil fumarate-containing PrEP was associated with significantly greater bone loss compared with maraviroc emtricitabine PrEP at the hip, but not the LS. The BMD changes at the hip were similar in magnitude in men and women.

A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections

Sci Adv

2021 Andrew Konecny; Jennifer Lund; Sarah Vick; Marie Frutoso; Raphael Gottardo; Florian Mair; Martin Prlic; Jim Boonyaratanakornkit; Evan Greene; Joshua Schiffer

[Figure: see text].

Adjuvant pembrolizumab versus interferon alfa-2b or ipilimumab in resected high-risk melanoma

Cancer Discov

2021 Megan Othus; James Moon; Hongli Li

We conducted a randomized phase 3 trial to evaluate whether adjuvant pembrolizumab for one year (648 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison to high-dose interferon alfa-2b for one year or ipilimumab for up to three years (655 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies (hazard ratio [HR] 0.77; 99.62% confidence interval [CI] 0.59-0.99; P=0.002). There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI 0.61-1.09; P=0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with interferon alfa-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared to the prior standard-of-care immunotherapies for patients with high-risk resected melanoma.

Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association

Gynecol Oncol

2021 Holly Harris

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n=5350) and without ovarian cancer (n=7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR=1.19, 95% CI 1.09-1.31 and OR=1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR=1.04, 95% CI 0.94-1.16 and OR=1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR=0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR=0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.