Estimating heterogeneity of physical function treatment response to caloric restriction among older adults with obesity.

Clinical trials conventionally test aggregate mean differences and assume homogeneous variances across treatment groups. However, significant response heterogeneity may exist. The purpose of this study was to model treatment response variability using gait speed change among older adults participating in caloric restriction (CR) trials. Eight randomized controlled trials (RCTs) with five- or six-month assessments were pooled, including 749 participants randomized to CR and 594 participants randomized to non-CR (NoCR). Statistical models compared means and variances by CR assignment and exercise assignment or select subgroups, testing for treatment differences and interactions for mean changes and standard deviations. Continuous equivalents of dichotomized variables were also fit. Models used a Bayesian framework, and posterior estimates were presented as means and 95% Bayesian credible intervals (BCI). At baseline, participants were 67.7 (SD = 5.4) years, 69.8% female, and 79.2% white, with a BMI of 33.9 (4.4) kg/m2. CR participants reduced body mass [CR: -7.7 (5.8) kg vs. NoCR: -0.9 (3.5) kg] and increased gait speed [CR: +0.10 (0.16) m/s vs. NoCR: +0.07 (0.15) m/s] more than NoCR participants. There were no treatment differences in gait speed change standard deviations [CR-NoCR: -0.002 m/s (95% BCI: -0.013, 0.009)]. Significant mean interactions between CR and exercise assignment [0.037 m/s (95% BCI: 0.004, 0.070)], BMI [0.034 m/s (95% BCI: 0.003, 0.066)], and IL-6 [0.041 m/s (95% BCI: 0.009, 0.073)] were observed, while variance interactions were observed between CR and exercise assignment [-0.458 m/s (95% BCI: -0.783, -0.138)], age [-0.557 m/s (95% BCI: -0.900, -0.221)], and gait speed [-0.530 m/s (95% BCI: -1.018, -0.062)] subgroups. Caloric restriction plus exercise yielded the greatest gait speed benefit among older adults with obesity. High BMI and IL-6 subgroups also improved gait speed in response to CR. Results provide a novel statistical framework for identifying treatment heterogeneity in RCTs.

Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health: Trial Design and Methods.

BACKGROUND: Achievement of 5-10% weight loss (WL) among older adults living with obesity considerably improves prognosis of health-related outcomes; however, concomitant declines in bone mineral density (BMD) limit overall benefit by increasing fracture risk. Declines in mechanical loading contribute to WL-associated BMD loss, with pilot data signaling the addition of external weight replacement (via weighted vest use) during intentional WL mitigates bone loss at weight bearing sites to a similar degree as resistance exercise training (RT). Definitive data in support of weighted vest use as a potential strategy to mitigate WL-associated bone loss in this population are needed. METHODS: In the Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health trial (NCT04076618), 192 older adults (60-85 years) who are overweight (BMI ≥ 27 kg/m2) with at least one obesity-related risk factor or obese (BMI = 30-40 kg/m2) will be randomly assigned to participate in one of three 12-month intervention groups: WL alone, WL + weighted vest use (WL + VEST), or WL + RT. The primary aim is to determine the effects of WL + VEST compared to WL alone and WL + RT on indicators of bone health and subsequent fracture risk. DISCUSSION: Determining effective, translatable strategies that minimize bone loss during intentional WL among older adults holds public health potential. The INVEST in Bone Health trial offers an innovative approach for increasing mechanical stress during intentional WL in the absence of RT. If successful, findings from this study will provide evidence in support of a scalable solution to minimize bone loss during intentional WL among older adults with obesity.

Gait variability is altered in cancer survivors with self-reported neuropathy.

BACKGROUND: Falls are prevalent among cancer survivors, and neuropathy, a side effect from chemotherapy treatment, is thought to contribute to falls. While falls commonly occur during walking, there is limited information about gait function in cancer survivors with neuropathy. RESEARCH QUESTION: What is the difference between gait speed and gait variability in cancer survivors with and without self-reported neuropathy and healthy controls? METHODS: Seventeen cancer survivors and 12 healthy individuals [age: 53.5 (11.8), gender: 10 females] participated in a single testing session. Cancer survivors were grouped into neuropathy [n = 9; age: 61.9 (6.1); gender: 8 females] and no neuropathy [n = 8; age: 50.75 (14.1); gender: 7 females] based on the self-reported FACT/GOG Neurotoxicity subscale questionnaire. All participants completed two walking trials at their comfortable pace across a 6 m pressure sensitive walkway. A one-way ANOVA with Tukey's post-hoc analysis and effect sizes were used to detect differences in gait speed, step length variability, and step width variability between groups. RESULTS: Although there were no group differences in gait speed, a significant main effect was found for step length variability (p =  0.03, η2 = 0.24) between groups. Step length variability was significantly less in cancer survivors with neuropathy than healthy controls (p = 0.05, d = 1.30). There was a significant main effect for step width variability between groups (p = 0.05, η2 = 0.20). Cancer survivors with neuropathy had significantly greater step width variability than healthy controls (p = 0.04, d = 1.04). SIGNIFICANCE: Cancer survivors with neuropathy display greater step width variability and less step length variability than healthy controls. Gait variability may be a more sensitive marker than gait speed to track mobility in cancer survivors with neuropathy symptoms. Assessing and treating gait function in cancer survivors with neuropathy symptoms may improve everyday ambulation.

Gait and Balance Impairments in Breast Cancer Survivors: A Systematic Review and Meta-analysis of Observational Studies.

OBJECTIVE: To systematically review and quantitatively synthesize gait and balance impairments in breast cancer survivors compared with age-matched controls or normative values for adults who never had breast cancer. DATA SOURCES: PubMed, Cumulative Index of Nursing and Allied Health, and Web of Science was searched using terms associated with breast cancer, mobility, and adult until November 2018. STUDY SELECTION: Studies were included if they were randomized control trials, cross-sectional, prospective, pre-post, or case-control by design, included adult breast cancer survivors, reported gait and/or balance metrics as primary or secondary outcomes, were peer-reviewed publications, and were written in English. The search yielded 2117 results with 29 studies meeting the inclusion criteria. DATA EXTRACTION: Two reviewers assessed study quality by the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to determine the strength of evidence for each study that met the inclusion criteria. Basic descriptors of each study, study protocol, and balance and gait measures were extracted. Meta-analysis was performed for the single leg stance, functional reach, center of pressure velocity, gait speed, and timed up and go. DATA SYNTHESIS: For quality assessment, 3 studies were rated good, 16 fair, and 10 poor. The meta-analysis indicated that there were no significant differences in single leg stance between breast cancer survivors and those who never had breast cancer (P=.33). Pooled values of the functional reach task (22.16cm; 95% CI, 8.98-35.33) and center of pressure velocity (1.2cm/s; 95% CI, 0.87-1.55) suggest balance impairment in breast cancer survivors when compared with normative values. Breast cancer survivors also performed worse than those who never had breast cancer in challenging balance conditions that reduced sensory information or altered base of support. Pooled gait speed at a usual speed (0.91m/s; 95% CI, 0.2-1.6), fast speed across a short distance (1.2m/s; 95% CI, 0.31-2.1), and fast gait speed across a long distance (1.65m/s; 95% CI, 1.64-1.66) suggest gait impairments when compared with normative values. CONCLUSIONS: Breast cancer survivors may demonstrate gait and balance impairments compared with normative values. Clinicians should consider assessing changes in balance and gait in breast cancer survivors to improve functional independence and prevent fall-related injuries.