A rapid point-of-care ultrasound marker for muscle mass and muscle strength in older adults.

BACKGROUND/OBJECTIVES: Sarcopenia is defined as the gradual age-associated loss of both muscle quantity and strength in older adults, and is associated with increased mortality, falls, fractures and hospitalisations. Current sarcopenia criteria use dual-energy X-ray absorptiometry (DXA) measures of muscle mass, a test that cannot be performed at the bedside, unlike point-of-care ultrasound (PoCUS). We examined the association between ultrasonic measures of muscle thickness (MT, vastus medialis muscle thickness) and measures of muscle quantity and strength in older adults. METHODS: A total of 150 older adults (age ≥ 65; mean age 80.0 ± 0.5 years, 66 women, 84 men) were recruited sequentially from geriatric medicine clinics. Each subject had lean body mass (LBM, by bioimpedance assay), grip strength, mid-arm biceps circumference (MABC), gait speed and MT measured. All initial models were adjusted for biological sex. RESULTS: In our final parsimonious models, MT showed a strong significant correlation with all measures of muscle mass, including LBM (Standardised ß = 0.204 ± 0.058, R2 = 0.577, P < 0.001) and MABC (Standardised ß = 0.141 ± 0.067, R2 = 0.417, P = 0.038). With respect to measures of muscle quality, there was a strong significant correlation with grip strength (Standardised ß = 0.118 ± 0.115, R2 = 0.511, P < 0.001) but not with subject performance (gait speed). CONCLUSIONS: MT showed strong correlations with both measures of muscle mass (LBM and MABC) and with muscle strength (grip strength). Although more work needs to be done, PoCUS shows potential as a screening tool for sarcopenia in older adults.

Baroreflex function and postprandial hypotension in older adults.

PURPOSE: Postprandial hypotension (PPH) is a common but poorly understood etiology for fainting in older adults. One potential mechanism is age-related baroreflex dysfunction. We examined baroreflex function in older adults with PPH and without PPH (noPPH) during a standardized meal test. METHODS: 57 adults (age ≥ 65; 24 PPH, 33 noPPH, mean age 77.9 ± 0.9 years, 54% female) were recruited and had meal tests performed. The baroreflex effectiveness index (BEI, %) and baroreflex sensitivity (BRS, ms/mm Hg) were calculated using the sequence method. RESULTS: Baseline BEI (22 ± 2 versus 23 ± 2 percent, t = - 0.411, p = 0.682) and BRS (14.1 ± 2.4 versus 13.8 ± 2.5 ms/mm of Hg, t = - 0.084, p = 0.933) were similar in PPH and noPPH subjects. During the meal test PPH subjects showed significantly lower BEI as compared to noPPH subjects (time × PPH, F = 2.791, p = 0.042), while there was no difference in the postprandial change in BRS (time, F = 0.618, p = 0.605). CONCLUSION: Patients with PPH demonstrated an acute postprandial decrease in baroreflex effectiveness during meal testing as compared with normal subjects, suggesting a potential contributing mechanism for this condition.

Blood pressure measurement and the prevalence of postprandial hypotension.

BACKGROUND: Postprandial hypotension (PPH) is a serious condition that has been shown to be an independent risk factor for falls, fractures and death. PURPOSE: The prevalence of this problem in older adults with a past history of falls has shown a wide variability in the literature; the present study seeks to examine how the frequency with which blood pressure is measured impacts the prevalence and severity of PPH. METHODS: Older adults were recruited sequentially from a geriatric medicine falls clinic for meal testing (n=95). All subjects (mean age 77.5±0.7 years, 61±5% female) were fasting prior to each 90 min standardized meal test. A Finometer (Finapres Medical Systems BV) was used to monitor blood pressure. Beat-by-beat systolic (SBP) measures were averaged for 0.5, 1, 2, 3, 5, 6, 9, 10, 15, 18, 30, 45 and 90 min respectively during the meal test. RESULTS: Using the original diagnostic method of checking mean blood pressure every 10 min resulted in a PPH prevalence of 42.1±5.1% in our population, with an overall range from 81.1±4.0% to 11.6±3.3% depending on the frequency of calculating SBP. The maximal observed postprandial decrease in SBP also showed a significant difference with blood pressure measurement frequency (p.

Frailty, Body Composition, and Glycemic Control in Older Adults with Type 2 Diabetes.

The relationship between frailty and glycemic control in older adults with diabetes remains uncertain, mainly due to the fact that previous studies have not accounted for measures of body composition. In older adults with diabetes, we examined the association between three types of frailty measures and glycemic control, while accounting for fat-free mass (FFM) and waist circumference (WC). Eighty older adults (age ≥65, 27 women and 53 men, mean age 80.5 ± 0.6 years) had gait speed, Cardiovascular Health Study Index (CHSI), Rockwood Clinical Frailty Scale (RCFS), and glycosylated hemoglobin (HgA1C) measured. HgA1C showed a negative association only with CHSI (standardized ß = -0.255 ± 0.120, p = 0.038), but no association with gait speed or the RCFS. Even after accounting for FFM and WC, we demonstrated a negative association between glycated hemoglobin and increasing frailty in older adults with diabetes.

Sleep efficiency and the metabolic risk score in very active older women and men.

Study Objectives: Sleep disruption is a risk factor for obesity, diabetes, and cardiovascular disease in older adults. How physical activity (PA) interacts with the negative cardiometabolic effects of poor sleep is not known. We objectively measured sleep efficiency (SE) in very active older adults and examined the association between SE and a continuous Metabolic Syndrome Risk Score (cMSy). Methods: Very active older adults (age ≥65 years) from a Master's Ski Team (Whistler, Canada) were recruited. Each participants wore an activity monitor (SenseWear Pro) continuously for 7 days to provide measures of both daily energy expenditure (metabolic equivalents, METs) and SE. All components of the metabolic syndrome were measured and a principal component analysis was used to compute a continuous metabolic risk score (cMSy, sum of eigenvalues ≥1.0). Results: A total of 54 participants (mean age 71.4 years, SD 4.4 years, and 24 men and 30 women) were recruited and had very high PA levels (>2.5 h per day of exercise). Initially, there was no significant association between SE and cMSy (p = 0.222). When stratified by biological sex, only men showed a significant negative association between SE and cMSy (Standardized ß = -0.364 ± 0.159, p = 0.032). Conclusions: Only older men show a significant negative association between poor SE and increased cardiometabolic risk, despite high levels of PA.

Effects of hypoxia-inducible factor-1alpha overexpression in pregnant mice: possible implications for preeclampsia and intrauterine growth restriction.

Preeclampsia and intrauterine growth restriction (IUGR) are pregnancy-specific disorders that share a common pathophysiology. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays an important role in placental development. HIF-1α is elevated in preeclamptic placentas and induces soluble vascular endothelial growth factor receptor-1 (sFLT-1), a central factor in preeclampsia and IUGR pathogenesis. Our objective was to investigate the effects of HIF-1α overexpression on pregnancy in mice. C57BL/6J pregnant mice were systemically administered either adenovirus expressing stabilized HIF-1α (cytomegalovirus [CMV]-HIF), luciferase control (CMV-Luc), or saline on gestational day 8. Pregnant mice overexpressing HIF-1α had significantly elevated blood pressure and proteinuria compared with pregnant controls. HIF-1α mice showed fetal IUGR, decreased placental weights, and histopathological placental abnormalities compared with control mice. Glomerular endotheliosis, the hallmark lesion of preeclampsia, was demonstrated in the kidneys of these mice relative to the normal histology in control mice. Moreover, liver enzyme levels were significantly elevated, whereas complete blood counts revealed significant anemia and thrombocytopenia in CMV-HIF mice compared with controls. Blood smears confirmed microangiopathic hemolytic anemia in CMV-HIF mice, consistent with HELLP (hemolysis, elevated liver enzymes, and low platelets)-like syndrome. CMV-HIF mice showed elevation in serum sFLT-1 and soluble endoglin, providing a mechanistic explanation for the observations. Collectively, our results suggest a possible role for HIF-1α in the pathogenesis of both preeclampsia and IUGR.

Anosmia-related internet search and the course of the first wave of the COVID-19 pandemic in the United States.

BACKGROUND: The current pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China. Although the first case in the United States was reported on Jan 20, 2020 in Washington, the early pandemic time course is uncertain. One approach with the potential to provide more insight into this time course is the examination of search activity. This study analyzed US search data prior to the first press release of anosmia as an early symptom (March 20, 2020). METHODS: Daily internet search query data was obtained from Google Trends (September 20th to March 20th for 2015 to 2020) both for the United States and on a state-by-state basis. Normalized anosmia-related search activity for the years prior to the pandemic was averaged to obtain a baseline level. Cross-correlations were performed to determine the time-lag between changes in search activity and SARS-CoV-2 cases/deaths. RESULTS: Only New York showed both significant increases in anosmia-related terms during the pandemic year as well as a significant lag (6 days) between increases in search activity and the number of cases/deaths attributed to SARS-CoV-2. CONCLUSIONS: There is no evidence from search activity to suggest earlier spread of SARS-CoV-2 than has been previously reported. The increase in anosmia-related searches preceded increases in SARS-CoV-2 cases/deaths by 6 days, but this was only significant over the background noise of searches for other reasons in the setting of a very large outbreak (New York in the spring of 2020).

Sedentary Time and Metabolic Risk in Extremely Active Older Adults.

OBJECTIVE: Increasing evidence suggests that time spent sedentary predicts increasing cardiometabolic risk independent of other physical activity. We objectively measured activity levels in active older adults and examined the association between sedentary behavior and the continuous metabolic syndrome risk score (cMSy). RESEARCH DESIGN AND METHODS: Older adults (age ≥65 years) were recruited from the Whistler Masters ski team, a group of active older adults who undergo organized group training. Daily activity levels were recorded with accelerometers (SenseWear) worn for 7 days. A compositional approach was used to determine proportion of the time spent sedentary as compared with all other nonsedentary behaviors (isometric log-ratio transformation for time spent sedentary [ILR1]). Waist circumference, triglycerides, HDL, systolic blood pressure, and fasting glucose were measured, and cMSy was calculated using principal component analysis (sum of eigenvalues ≥1.0). RESULTS: Fifty-four subjects (30 women and 24 men, mean ± SE age 71.4 ± 0.6 years) were recruited. Subjects demonstrated high levels of physical activity (2.6 ± 0.2 h light activity and 3.9 ± 0.2 h moderate/vigorous activity). In our final parsimonious model, ILR1 showed a significant positive association with increasing cMSy (standardized ß = 0.368 ± 0.110, R 2 = 0.40, P = 0.002), independent of age and biological sex. CONCLUSIONS: Despite high levels of activity, ILR1 demonstrated a strong association with cMSy. This suggests that even in active older adults, sedentary behavior is associated with increasing cardiometabolic risk.

Point-of-care ultrasound measures of muscle and frailty measures.

PURPOSE: Frailty is defined as a syndrome of increased vulnerability due to both age and disease that leads to an inability to cope with acute stressors. There has been growing interest in the surgical and emergency medicine literature in the potential use of Point-of-Care ultrasonic (PoCUS) measures of muscle mass to assess frailty in older adults. Our study examined the association between a simple ultrasonic measure of muscle thickness (MT, vastus medialis muscle thickness) and commonly used frailty measures (Cardiovascular Health Study, CHS; Rockwood Clinical Frailty Scale, RCFS) in older adults. METHODS: Participants were recruited sequentially from ambulatory geriatric medicine clinics in an academic medical centre (Vancouver General Hospital, Vancouver, Canada). Each subject had MT measured by PoCUS, as well as the CHS index and Rockwood Clinical Frailty Scale. RESULTS: 150 older adults (age ≥ 65; mean age 80.0 ± 0.5 years, 66 women, 84 men) were recruited. In our final parsimonious models, MT showed a weak inverse association with the CHS index (Standardized ß = - 0.180 ± 0.080, R2 = 0.06, p = 0.027) and no association with the RCFS (p = 0.776). Within the CHS index, most of the association was due to grip strength in men (Standardized ß = - 0.326 ± 0.099, R2 = 0.26, p = 0.001). CONCLUSION: Frailty is a multifactorial syndrome, and caution must be used in trying to screen for this condition with a single ultrasonic measure. Further work might indicate associations with a more restricted syndrome, such as sarcopenia.

Weekly, Seasonal, and Geographic Patterns in Health Contemplations About Sundown Syndrome: An Ecological Correlational Study.

BACKGROUND: Sundown syndrome (ie, agitation later in the day) is common in older adults with dementia. The underlying etiology for these behaviors is unclear. Possibilities include increased caregiver fatigue at the end of the day and disruption of circadian rhythms by both age and neurodegenerative illness. OBJECTIVE: This study sought to examine circumseptan (weekly) patterns in search volumes related to sundown syndrome, in order to determine if such searches peaked at the end of the weekend, a time when caregiver supports are least available. We also sought to examine both seasonal differences and associations of state-by-state search activity with both state latitude and yearly sun exposure. METHODS: Daily Internet search query data was obtained from Google Trends (2005-2017 inclusive). Circumseptan patterns were determined by wavelet analysis, and seasonality was determined by the difference in search volumes between winter (December, January, and February) and summer (June, July, and August) months. Geographic associations between percent sunny days and latitude were done on a state-by-state basis. RESULTS: "Sundowning" searches showed a significant increase at the end of the weekend with activity being 10.9% (SD 4.0) higher on Sunday as compared to the rest of the week. Search activity showed a seasonal pattern with search activity significantly highest in the winter months (36.6 [SD 0.6] vs 13.7 [SD 0.2], P<.001). State-by-state variations in "sundowning" searches showed a significant negative association with increasing mean daily sunlight (R2=.16, ß=-.429 [SD .149], P=.006) and showed a positive association with increasing latitude (R2=.38, ß=.648 [SD .122], P<.001). CONCLUSIONS: Interest in "sundowning" is highest after a weekend, which is a time when external caregiver support is reduced. Searches related to sundown syndrome also were highest in winter, in states with less sun, and in states at more northerly latitudes, supporting disrupted circadian rhythms as another contributing factor to these behaviors.

Characteristics Associated with the Postprandial Hypotensive Response in Falling Older Adults.

Il a été démontré que l'intensité de la réponse hypotensive postprandiale (RHP) peut constituer un facteur de risque pour les chutes, les fractures et le décès. Bien que ce risque ait été bien établi, les cliniques de chutes font rarement des analyses liées aux repas, en raison de contraintes logistiques. Afin de mieux cibler les patients à risque de RHP parmi les personnes âgées affectées par des chutes, cette étude a examiné les caractéristiques individuelles associées à des RHP plus intenses. Cinquante-deux patients (âge moyen : 77,8 ± 0,9 ans, 29 femmes, 23 hommes) référés par des cliniques de prévention des chutes ont été recrutés pour un repas-test de 90 minutes. Les variables significatives ont ensuite été insérées dans un modèle linéaire multivarié incluant l'âge, le sexe, la présence de diabète, la présence d'hypertension, la pression systolique de base (PSB) et la chute de la PSB orthostatique. Bien que de plus amples recherches soient nécessaires, notre étude suggère que les hommes, les patients présentant une tension artérielle élevée et ceux avec une chute orthostatique pourraient être plus à risque de réponses hémodynamiques postprandiales plus intenses.The magnitude of the postprandial hypotensive (PPH) response has been shown to be an independent risk factor for falls, fractures, and death. Despite this well-established risk, meal tests are rarely done in the falls clinic setting because of logistical issues. In order to better target potential PPH patients among older falling adults, this study examines which subject characteristics are associated with larger PPH responses. A total of 52 falls clinic patients (mean age 77.8 ± 0.9 years, 29 women, 23 men) were recruited for a 90 minute meal test. Significant variables were then entered into a stepwise multivariate linear model containing age, sex, presence of diabetes, presence of hypertension, baseline systolic blood pressure (SBP), and the orthostatic drop in SBP. Although further work is required, our study suggests that men, patients with higher blood pressure, and patients with an orthostatic drop might be more likely to have higher postprandial hemodynamic responses.

Treatment with lecinoxoids attenuates focal and segmental glomerulosclerosis development in nephrectomized rats.

Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low-grade inflammation ascribed to toll-like receptor (TLR) activation and monocyte migration. We developed synthetic, small-molecule lecinoxoids, VB-201 and VB-703, that differentially inhibit TLR-2- and TLR-4-mediated activation and monocyte migration. The efficacy of anti-inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model. Five-sixths of nephrectomized rats were treated with lecinoxoids VB-201, VB-703 or PBS, for 7 weeks. Upon sacrifice, albumin/creatinine ratio, glomerulosclerosis, fibrosis-related gene expression and the number of glomerular and interstitial monocyte were evaluated. Treatment of nephrectomized rats with lecinoxoids ameliorated glomerulosclerosis. The percentage of damaged glomeruli, glomerular sclerosis and glomeruli fibrotic score was significantly reduced following VB-201 and VB-703 treatment. VB-703 attenuated the expression of fibrosis hallmark genes collagen, fibronectin (FN) and transforming growth factor ß (TGF-ß) in kidneys and improved albumin/creatinine ratio with higher efficacy than did VB-201, but only VB-201 significantly reduced the number of glomerular and interstitial monocytes. These results indicate that treatment with TLR-2, and more prominently, TLR-4 antagonizing lecinoxioids, is sufficient to significantly inhibit FSGS. Moreover, inhibiting monocyte migration can also contribute to treatment of FSGS. Our data demonstrate that targeting TLR-2-TLR-4 and/or monocyte migration directly affects the priming phase of fibrosis and may consequently perturb disease parthogenesis.

Amantadine as augmentation therapy in the management of treatment-resistant depression.

Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry. While several strategies have been attempted, including medication switch, antidepressant polypharmacy and various augmentative regimens, success remains limited. Amantadine (AMN), an agent traditionally used in the treatment and prophylaxis of influenza, is now known to exhibit prominent effects at the level of dopaminergic, monoamine oxidase and N-methyl-D-aspartate systems. The present reports on the efficacy of AMN as augmentation to standard antidepressant treatment in patients with treatment-resistant depression. Eight patients with treatment-resistant depression consented to receive AMN, titrated up to a dose of 300 mg, over a period of 4 weeks in a non-blinded fashion. Improvement in both depression and anxiety scores were observed from week 1, with patients exhibiting improvement of depressive scores of up to 49% by study completion. Females appeared to exhibit a stronger response, and within a shorter period of time. Side-effects reported included dry mouth and sedation. AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression. Further studies are clearly mandated to test these preliminary observations in a double-blinded manner.