Physical Function Effects of Live Video Group Exercise Interventions for Older Adults: A Systematic Review and Veteran's Gerofit Group Case Study.

Background: Literature on telehealth interventions for older adults has been primarily on asynchronous interventions. During the COVID-19 pandemic, older adult exercise programs transitioned to an online format. This systematic review and case study examines the effectiveness of older adult live video exercise group interventions on physical health with insights from a Los Angeles VA program, Gerofit. Methods: PubMed was searched for live video older adult exercise groups from database inception to November 2021. All eligible studies included assessments of physical health and were limited to participants with an average age of 65 years or greater. Ten Veterans, who had participated in both in-person and virtual Gerofit sessions, were surveyed in the case study. Results: Nine studies met the inclusion criteria. Four studies included an equivalent in-person group as a comparator to the live video group and reported no significant between-group differences in outcomes, including energy expenditure and 6-minute walking distance test (6MWD). The other five studies reported statistically significant in-group improvement in outcomes including isokinetic knee strength. Case study participants reported similar attendance rates and perceived benefits, such as improved balance, when comparing virtual and in-person sessions. Discussion: Live video exercise groups in older adults demonstrated an improvement in physical function that was not statistically different from the comparison in-person sessions with the added benefit of averaging a higher attendance rate, providing initial support for the use of live video in older adult exercise programs. Insights from the case study supplement this by demonstrating older adults' positive attitude on these groups.

Mitochondrial DNA deletion mutations increase exponentially with age in human skeletal muscle.

BACKGROUND: Mitochondrial DNA (mtDNA) deletion mutations lead to electron transport chain-deficient cells and age-induced cell loss in multiple tissues and mammalian species. Accurate quantitation of somatic mtDNA deletion mutations could serve as an index of age-induced cell loss. Quantitation of mtDNA deletion molecules is confounded by their low abundance in tissue homogenates, the diversity of deletion breakpoints, stochastic accumulation in single cells, and mosaic distribution between cells. AIMS: Translate a pre-clinical assay to quantitate mtDNA deletions for use in human DNA samples, with technical and biological validation, and test this assay on human subjects of different ages. METHODS: We developed and validated a high-throughput droplet digital PCR assay that quantitates human mtDNA deletion frequency. RESULTS: Analysis of human quadriceps muscle samples from 14 male subjects demonstrated that mtDNA deletion frequency increases exponentially with age-on average, a 98-fold increase from age 20-80. Sequence analysis of amplification products confirmed the specificity of the assay for human mtDNA deletion breakpoints. Titration of synthetic mutation mixtures found a lower limit of detection of at least 0.6 parts per million. Using muscle DNA from 6-month-old mtDNA mutator mice, we measured a 6.4-fold increase in mtDNA deletion frequency (i.e., compared to wild-type mice), biologically validating the approach. DISCUSSION/CONCLUSIONS: The exponential increase in mtDNA deletion frequency is concomitant with the known muscle fiber loss and accelerating mortality that occurs with age. The improved assay permits the accurate and sensitive quantification of deletion mutations from DNA samples and is sufficient to measure changes in mtDNA deletion mutation frequency in healthy individuals across the lifespan and, therefore, patients with suspected mitochondrial diseases.

An innovative educational clinical experience promoting geriatric exercise.

Formal educational training in physical activity promotion is relatively sparse throughout the medical education system. The authors describe an innovative clinical experience in physical activity directed at medical clinicians on a geriatrics rotation. The experience consists of a single 2 1/2 hour session, in which learners are partnered with geriatric patients engaged in a formal supervised exercise program. The learners are guided through an evidence-based exercise regimen tailored to functional status. This experience provides learners with an opportunity to interact with geriatric patients outside the hospital environment to counterbalance the typical geriatric rotation in which geriatric patients are often seen in clinics or hospitals. In this experience, learners are exposed to fit and engaged geriatric patients successfully living in the community despite chronic or disabling conditions. A survey of 105 learners highlighted positive responses to the experience, with 96% of survey respondents indicating that the experience increased their confidence in their ability to serve as advocates for physical activity for older adults, and 89.5% of responders to a follow-up survey indicating that the experience changed their perception of geriatric patients. Modifications to the experience, implemented at partnering facilities are described. The positive feedback from this experience warrants consideration for implementation in other settings.

Mobility Improvements are Found in Older Veterans After 6-Months of Gerofit Regardless of BMI Classification.

Veterans represent a unique population of older adults as they are more likely to self-report disability and be overweight or obese compared to the general population. We sought to compare changes in mobility function across the obesity spectrum in older Veterans participating in six-months of Gerofit, a clinical exercise program. 270 Veterans completed baseline, three, and six-month functional assessment and were divided post-hoc into groups: normal weight, overweight, and obese. Physical function assessment included: ten-meter walk time, six-minute walk distance, 30-second chair stands, and eight-foot up-and-go time. No significant weight x time interactions were found for any measure. However, significant (P<0.02) improvements were found for all mobility measures from baseline to three-months and maintained at six-months. Six-months of participation in Gerofit, if enacted nationwide, appears to be one way to improve mobility and function in older Veterans at high risk for disability regardless of weight status.

A pilot validation of multi-echo based echo-planar correlated spectroscopic imaging in human calf muscles.

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single-voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D.

Risk of cardiovascular disease among postmenopausal women with prior pregnancy loss: the women's health initiative.

PURPOSE: Metabolic, hormonal, and hemostatic changes associated with pregnancy loss (stillbirth and miscarriage) may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between a history of pregnancy loss and CVD in a cohort of postmenopausal women. METHODS: Postmenopausal women (77,701) were evaluated from 1993-1998. Information on baseline reproductive history, sociodemographic, and CVD risk factors were collected. The associations between 1 or 2 or more miscarriages and 1 or more stillbirths with occurrence of CVD were evaluated using multiple logistic regression. RESULTS: Among 77,701 women in the study sample, 23,538 (30.3%) reported a history of miscarriage; 1,670 (2.2%) reported a history of stillbirth; and 1,673 (2.2%) reported a history of both miscarriage and stillbirth. Multivariable-adjusted odds ratio (OR) for coronary heart disease (CHD) for 1 or more stillbirths was 1.27 (95% CI, 1.07-1.51) compared with no stillbirth; for women with a history of 1 miscarriage, the OR=1.19 (95% CI, 1.08-1.32); and for 2 or more miscarriages the OR=1.18 (95% CI, 1.04-1.34) compared with no miscarriage. For ischemic stroke, the multivariable odds ratio for stillbirths and miscarriages was not significant. CONCLUSIONS: Pregnancy loss was associated with CHD but not ischemic stroke. Women with a history of 1 or more stillbirths or 1 or more miscarriages appear to be at increased risk of future CVD and should be considered candidates for closer surveillance and/or early intervention; research is needed into better understanding the pathophysiologic mechanisms behind the increased risk of CVD associated with pregnancy loss.

Associations of appendicular lean mass and abdominal adiposity with insulin resistance in older adults: A cross-sectional study.

Loss of lean muscle mass and accumulation of adipose tissue are changes associated with aging. Previous studies have documented various components of body composition as predictors for insulin resistance. The objective of this study was to investigate whether components of body composition-appendicular lean mass (ALM) and/or abdominal fat mass (AFM)-correlate with insulin resistance in older men and women. This was a cross-sectional study of 92 older men and women. Weight was classified according to body mass index (BMI)-normal (BMI <25), overweight (BMI 25-30), and obese (BMI >30). All body composition data was determined by dual energy x-ray absorptiometry (DEXA), and insulin resistance was assessed by the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable regression models with two-way interaction terms were employed to assess whether the associations between components of body composition and log HOMA varied by BMI categories. Adjusted regression showed that log HOMA was significantly associated with AFM (estimate ± standard error: 0.055 ± 0.026) and ALM (0.057 ± 0.029) for the overweight participants (p-values <0.05). Additionally, the adjusted associations between log HOMA and ALM were significantly greater for participants who were either obese or overweight compared to those with a normal BMI (p<0.002). Less consistent relationships were observed between insulin resistance and abdominal fat mass across BMI categories, whereas more consistent associations were observed between insulin resistance and appendicular lean mass in individuals with greater BMI. Further research is needed to clarify if lipid deposition within muscle tissue promotes muscle dysfunction and thereby increases risk for insulin resistance.

Longitudinal analysis of physical function in older adults: The effects of physical inactivity and exercise training.

Lack of exercise contributes to systemic inflammation and is a major cause of chronic disease. The long-term impact of initiating and sustaining exercise in late life, as opposed to sustaining a sedentary lifestyle, on whole-body health measures such as physical performance is not well known. This is an exploratory study to compare changes in physical performance among older adults initiating exercise late in life versus inactive older adults. Data from two observational cohorts were included in this analysis, representing two activity groups. The Active group cohort comprises older adults (n = 318; age 72.5 ± 7.2 years) enrolled in a supervised exercise program, "Gerofit." The inactive group comprises older adults (n = 146; age 74.5 ± 5.5 years) from the Italian study "Act on Ageing" (AOA) who self-reported being inactive. Participants in both groups completed physical performance battery at baseline and 1-year including: 6-min walk test, 30-s chair stand, and timed up-and-go. Two-sample t-tests measured differences between Gerofit and AOA at baseline and 1-year across all measures. Significant between-group effects were seen for all performance measures (ps = 0.001). The AOA group declined across all measures from baseline to 1 year (range -18% to -24% change). The Gerofit group experienced significant gains in function for all measures (range +10% to +31% change). Older adults who initiated routine, sustained exercise were protected from age-related declines in physical performance, while those who remained sedentary suffered cumulative deficits across strength, aerobic endurance, and mobility. Interventions to reduce sedentary behaviors and increase physical activity are both important to promote multi-system, whole-body health.

Smoking and diabetes: does the increased risk ever go away?

Recent studies reported that smoking cessation leads to higher short-term risk of type 2 diabetes than continuing to smoke. However, the duration of increased diabetes risk following smoking cessation needs further investigation. We followed 135,906 postmenopausal women aged 50-79 years enrolled in the Women's Health Initiative between September 1, 1993, and December 31, 1998, over an average of 11 years to examine the association between smoking cessation and risk of diabetes using Cox proportional hazard multivariable-adjusted regression models. Compared with that for never smokers, the risk for diabetes was significantly elevated in current smokers (hazard ratio = 1.28, 95% confidence interval: 1.20, 1.36) but was even higher in women who quit smoking during the first 3 years of follow-up (hazard ratio = 1.43, 95% confidence interval: 1.26, 1.63). Among former smokers, the risk of diabetes decreased significantly as the time since quitting increased and was equal to that of never smokers following a cessation period of 10 years. In new quitters with low cumulative exposure (<20 pack-years), diabetes risk was not elevated following smoking cessation. In conclusion, the risk of diabetes in former smokers returns to that in never smokers 10 years after quitting, and even more quickly in lighter smokers.

Nanopore sequencing identifies a higher frequency and expanded spectrum of mitochondrial DNA deletion mutations in human aging.

Mitochondrial DNA (mtDNA) deletion mutations cause many human diseases and are linked to age-induced mitochondrial dysfunction. Mapping the mutation spectrum and quantifying mtDNA deletion mutation frequency is challenging with next-generation sequencing methods. We hypothesized that long-read sequencing of human mtDNA across the lifespan would detect a broader spectrum of mtDNA rearrangements and provide a more accurate measurement of their frequency. We employed nanopore Cas9-targeted sequencing (nCATS) to map and quantitate mtDNA deletion mutations and develop analyses that are fit-for-purpose. We analyzed total DNA from vastus lateralis muscle in 15 males ranging from 20 to 81 years of age and substantia nigra from three 20-year-old and three 79-year-old men. We found that mtDNA deletion mutations detected by nCATS increased exponentially with age and mapped to a wider region of the mitochondrial genome than previously reported. Using simulated data, we observed that large deletions are often reported as chimeric alignments. To address this, we developed two algorithms for deletion identification which yield consistent deletion mapping and identify both previously reported and novel mtDNA deletion breakpoints. The identified mtDNA deletion frequency measured by nCATS correlates strongly with chronological age and predicts the deletion frequency as measured by digital PCR approaches. In substantia nigra, we observed a similar frequency of age-related mtDNA deletions to those observed in muscle samples, but noted a distinct spectrum of deletion breakpoints. NCATS-mtDNA sequencing allows the identification of mtDNA deletions on a single-molecule level, characterizing the strong relationship between mtDNA deletion frequency and chronological aging.

Sex hormone-binding globulin and risk of type 2 diabetes in women and men.

BACKGROUND: Circulating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. METHODS: We performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). RESULTS: Among women, higher plasma levels of sex hormone-binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone-binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone-binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex hormone-binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex hormone-binding globulin may have a causal role in the risk of type 2 diabetes. CONCLUSIONS: Low circulating levels of sex hormone-binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination.

Skeletal muscle mitochondrial DNA copy number and mitochondrial DNA deletion mutation frequency as predictors of physical performance in older men and women.

Mitochondrial DNA (mtDNA) quality and quantity relate to two hallmarks of aging-genomic instability and mitochondrial dysfunction. Physical performance relies on mitochondrial integrity and declines with age, yet the interactions between mtDNA quantity, quality, and physical performance are unclear. Using a validated digital PCR assay specific for mtDNA deletions, we tested the hypothesis that skeletal muscle mtDNA deletion mutation frequency (i.e., a measure of mtDNA quality) or mtDNA copy number predicts physical performance in older adults. Total DNA was isolated from vastus lateralis muscle biopsies and used to quantitate mtDNA copy number and mtDNA deletion frequency by digital PCR. The biopsies were obtained from a cross-sectional cohort of 53 adults aged 50 to 86 years. Before the biopsy procedure, physical performance measurements were collected, including VO2max, modified physical performance test score, 6-min walk distance, gait speed, grip strength, and total lean and leg mass. Linear regression models were used to evaluate the relationships between age, sex, and the outcomes. We found that mtDNA deletion mutation frequency increased exponentially with advancing age. On average from ages 50 to 86, deletion frequency increased from 0.008 to 0.15%, an 18-fold increase. Females may have lower deletion frequencies than males at older ages. We also measured declines in VO2max and mtDNA copy number with age in both sexes. The mtDNA deletion frequency measured from single skeletal muscle biopsies predicted 13.3% of the variation in VO2max. Copy number explained 22.6% of the variation in mtDNA deletion frequency and 10.4% of the lean mass variation. We found predictive relationships between age, mtDNA deletion mutation frequency, mtDNA copy number, and physical performance. These data are consistent with a role for mitochondrial function and genome integrity in maintaining physical performance with age. Analyses of mtDNA quality and quantity in larger cohorts and longitudinal studies could extend our understanding of the importance of mitochondrial DNA in human aging and longevity.

PTSD Improvement Associated with Social Connectedness in Gerofit Veterans Exercise Program.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is common in Veterans. Symptoms can perpetuate into late life, negatively impacting physical and mental health. Exercise and social support are beneficial in treating anxiety disorders such as PTSD in the general population, although less is known about the impact on Veterans who have lived with PTSD for decades. This study assessed associations between social connectedness, physical function and self-reported change in PTSD symptoms among older Veterans specifically participating in Gerofit. DESIGN: Prospective clinical intervention. SETTING: Twelve sites of Veterans Affairs (VA) Gerofit exercise program across the United States. PARTICIPANTS: Three hundred and twenty one older Veteran Gerofit participants (mean age = 74) completed physical assessments and questionnaires regarding physical and emotional symptoms and their experience. MEASUREMENTS: Measures of physical function, including 30-second chair stands, 10-m and 6-min walk were assessed at baseline and 3 months; change in PTSD symptoms based on the Diagnostic Statistical Manual-5 (DSM-5) assessed by a self-report questionnaire; and social connection measured by the Relatedness Subscale of the Psychological Need Satisfaction in Exercise scale (PNSE) were evaluated after 3 months of participation in Gerofit. RESULTS: Ninety five (29.6%) Veterans reported PTSD. Significant improvement was noted in self-rated PTSD symptoms at 3 months (P < .05). Moderate correlation (r = .44) was found between social connectedness with other participants in Gerofit and PTSD symptom improvement for those Veterans who endorsed improvement (n = 59). All participants improved on measures of physical function. In Veterans who endorsed PTSD there were no significant associations between physical function improvement and PTSD symptoms. CONCLUSION: Veterans with PTSD that participated in Gerofit group exercise reported symptom improvement, and social connectedness was significantly associated with this improvement. In addition to physical health benefits, the social context of Gerofit may offer a potential resource for improving PTSD symptoms in older Veterans that warrants further study.

Enhanced Methods for Needle Biopsy and Cryopreservation of Skeletal Muscle in Older Adults.

Human muscle biopsies are increasingly important for diagnosis, research, and to monitor therapeutic trials. We examined the use of a self-contained, vacuum-assisted biopsy system and a novel muscle freezing technique to improve, simplify, and standardize human muscle biopsy collection and cryopreservation in older adults. The VACORA vacuum-assisted biopsy system was deployed in muscle biopsies of 12 individuals ranging in age from 57 to 80 years. This office-based approach was well tolerated as it is minimally invasive, uses only local anesthetic, and has a quick recovery. To maximize biopsy sample quality and reproducibility, we developed a novel muscle sample freezing protocol. Fresh muscle biopsy samples were placed into readily available tissue cassettes followed by direct freezing in liquid nitrogen. After this modified snap freezing protocol, frozen muscle samples were enrobed in embedding medium for cryosectioning. We examined the effect of this freezing approach in histological sections of rodent and human muscle samples. The VACORA Biopsy System provided as many as four skeletal muscle core samples from a single biopsy site. Biopsy samples from 12 older adults weighed an average of 147.5 ± 11 mg each and had a consistent size and shape. There were no complications, and the residual scar is less than 10 mm. The freezing method using standard tissue cassettes with direct freezing in liquid nitrogen yielded high quality cryopreserved muscle tissue suitable for histological analysis without the need for isopentane and with little to no freeze-thaw damage. These enhancements have streamlined and improved the consistency of our muscle biopsy protocol and provide sufficient high-quality sample for multi-dimensional downstream studies of human muscle in aging and disease.

Caring for older veterans with chronic low back pain using a geriatric syndrome approach: Rationale and methods for the aging back clinics (ABC) trial.

The purpose of the ongoing trial is to improve care of older Veterans with chronic low back pain (CLBP, i.e., low back pain for ≥6 months on ≥ half the days). Current CLBP care is limited by being either overly spine-focused or non-specifically prescribed and both approaches frequently lead to suboptimal reduction in pain and improvement in function. Through prior studies we have laid the foundation for a patient-centered approach to care for older Veterans with CLBP in which the spine is a source of vulnerability but not the sole treatment target. The approach considers CLBP a geriatric syndrome, a final common pathway for the expression of multiple contributors rather than a disease of the spine. We describe here the rationale and design of a randomized controlled trial to test the efficacy of an older Veteran-centered approach to CLBP care in "Aging Back Clinics (ABCs)" compared with Usual Care (UC). Three hundred thirty Veterans age 65-89 with CLBP will be randomized to ABCs or UC and followed for 12 months after randomization. We will assess the impact of ABCs on our primary outcome of pain-associated disability with the Oswestry Disability Index at 6 and 12 months, and secondary outcomes of pain intensity, health-related quality of life, balance confidence, mobility and healthcare utilization. If shown efficacious, the approach tested in ABCs has the potential to transform the care of older adults with CLBP by improving the quality of life for millions, reducing morbidity and saving substantial healthcare costs.

Rapid Transition to Telehealth Group Exercise and Functional Assessments in Response to COVID-19.

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants' physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects.

Relation of genetic variation in the gene coding for C-reactive protein with its plasma protein concentrations: findings from the Women's Health Initiative Observational Cohort.

BACKGROUND: Although common genetic variants of the CRP gene (C-reactive protein, pentraxin related) have been associated with plasma concentrations of high-sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few studies have comprehensively assessed this association in well-characterized multiethnic populations. METHODS: In a case-control study of diabetes nested in the Women's Health Initiative Observational Cohort, we comprehensively evaluated the association of genetic variation in CRP with plasma hsCRP concentrations. Thirteen haplotype-tagging single-nucleotide polymorphisms (tSNPs) were identified and subsequently genotyped in 3782 postmenopausal women. RESULTS: The allele frequencies for these tSNPs and the haplotype blocks defined by these tSNPs varied significantly by ethnic group (P < 0.0001). Consistent with prior studies of whites, rs3093068, rs1130864, and rs1417938 were significantly associated with higher hsCRP concentrations (geometric-mean increase per minor-allele change, 1.20-1.25 mg/L), and rs1205 and rs1800947 were significantly associated with lower hsCRP values (decrease of 1.28-1.48 mg/L). The associations with rs3093068 and rs1205 appeared to be stronger in Asians/Pacific Islanders than in whites (geometric-mean increase, 1.65 mg/L vs 1.25 mg/L, respectively). Minor alleles at rs3093075 and rs3093059 were associated with substantially increased hsCRP concentrations, whereas rs1800947 was associated with lower hsCRP values. All haplotype-based association results tended to be consistent with the associations seen with single CRP SNPs. CONCLUSIONS: Our large multiethnic case-control study of postmenopausal women provides evidence that common genetic variants in the CRP gene are substantially associated with plasma hsCRP concentrations in this case-control subcohort. The data also suggest ethnic variations in these associations.

Gerofit Prehabilitation Pilot Program: Preparing Frail Older Veterans for Surgery.

Older Veterans are increasingly undergoing surgery and are at particularly high risk of postoperative morbidity and mortality. Prehabilitation has emerged as a method to improve postoperative outcomes by enhancing the patient's preoperative condition. We present data from our prehabilitation pilot project and plans for expansion and dissemination of a nationwide quality improvement effort. The infrastructure of the existing Veterans Affairs (VA) Gerofit health and exercise program was used to create our pilot. Pilot patients were screened for risk of postoperative functional decline, assessed for baseline physical function, enrolled in a personalized exercise program, and prepared to transition into the hospital for surgery. Patients (n = 9) completed an average of 17.7 prehabilitation sessions. After completing the program, 55.6% improved in ≥2 of the 5 fitness assessments completed. Postoperative outcomes including complications, 30-day mortality, and 30-day readmissions were better than predicted by the National Surgical Quality Improvement Program Surgical Risk Calculator. We have obtained institutional support for implementing similar prehabilitation programs at VA hospitals nationally through our designation as a VA Patient Safety Center for Inquiry. This is the first multi-institutional prehabilitation program for frail, older Veterans and represents an essential step toward optimizing surgical care for this vulnerable population.

Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors.

AIMS: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. METHODS: Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m²) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. RESULTS: There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points (p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left (p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. CONCLUSIONS: CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.