Measuring frailty in clinical practice: a comparison of physical frailty assessment methods in a geriatric out-patient clinic.

BACKGROUND: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB. METHODS: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant. RESULTS: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002). CONCLUSIONS: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone.

PURPOSE: The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. METHODS: Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 µm(2)) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann-Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. RESULTS: Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5]years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4]years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98]wt.% Ca versus 19.40 [1.07]wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99-4.12]wt.% Ca versus 3.95 [0.71]wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97]wt.% Ca for type 2 diabetes versus 20.44 [1.30]wt.% Ca for controls, p=0.121). CONCLUSION: The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.

Ankle fractures do not predict osteoporotic fractures in women with or without diabetes.

UNLABELLED: It is not clear whether ankle fractures predict future osteoporotic fractures in women, and whether diabetes influences this relationship. We found that a prior ankle fracture does not predict subsequent osteoporotic fractures in women with or without diabetes. INTRODUCTION: We aimed to determine: (1) whether a prior ankle fracture was a risk factor for a subsequent major osteoporotic fracture in older women; (2) whether this risk was modified by the presence of diabetes; (3) the risk factors for ankle fracture in older women. METHODS: We identified 3,054 women age 50 years and older with diabetes and 9,151 matched controls using the Manitoba Bone Density Program database. Multivariable regression models were used to examine factors associated with prior ankle fracture, and the importance of prior ankle fracture as a predictor of subsequent major osteoporotic fracture during a mean 4.8 years of observation. RESULTS: A prior ankle fracture was not a significant predictor of subsequent major osteoporotic fracture for women with diabetes (hazard ratio [HR] 1.13; 95% confidence interval [CI], 0.68-1.83; p = 0.623) or women without diabetes (HR 1.16; 95% CI, 0.79-1.71; p = 0.460), and there was no interaction between diabetes and ankle fracture after pooling all women in the cohort (p = 0.971). The presence of diabetes was not independently associated with prior ankle fracture (adjusted odds ratio [OR] 1.14 [95% CI, 0.93-1.38], p = 0.200), whereas higher body mass index (adjusted OR 1.04 per standard deviation increase [95% CI, 1.03-1.06], p < 0.001), previous major osteoporotic fracture (adjusted OR 1.40 [95% CI, 1.13-1.75], p = 0.002), and multiple comorbidities (>6 ambulatory diagnostic groups) (adjusted OR 1.81 [95% CI, 1.40-2.36], p < 0.001) were related to prior ankle fracture. CONCLUSIONS: Ankle fracture was not a significant predictor of major osteoporotic fracture in women, and a diagnosis of diabetes did not influence the relationship.

New spiropiperidines as potent and selective non-peptide tachykinin NK2 receptor antagonists.

The synthesis of a series of 2-(5-fluoro-1H-indol-3-yl)ethyl spiropiperidines is described together with their tachykinin NK2 receptor affinities measured in a rat colon binding assay. Equivalent NK2 receptor binding affinity was observed for the spirooxazolidinone 3-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-1-oxa-3,8-diazaspiro[4.5] decan-2-one (3a), the imidazolidinone 3-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-1,3,8-triazaspiro[4.5 ] decan-2-one (3s), and the pyrrolidinone 2-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-2,8-diazaspiro[4.5]decan -3 - one (3t). Substitution in the phenyl ring of compound 3a produced no significant enhancement in NK2 binding affinity. Replacement of the phenyl ring in 3a with other aromatic rings resulted in a significant loss in binding affinity. Compound 3a was shown to be a potent NK2 receptor antagonist in guinea pig trachea where it also demonstrated 1000-fold selectivity for NK2 receptors over NK1. In the anesthetized guinea pig, compound 3a administered by the intravenous or oral route displayed potent and long-lasting antagonist activity against NK2 receptor agonist induced bronchoconstriction.

Nutritional status of light-for-date infants at birth and its influence on early postnatal growth.

The ponderal index (PI) (g/cm3 X 100) was used to define the state of nutrition at birth of 47 light-for-date (LFD) term infants and to determine how intrauterine undernutrition influences growth during the first 6 months of postnatal life, at four age intervals: birth--4, 5--8, 9--12, 13--26 weeks. With the exception of one baby, each PI was less than 50th centile on the Miller and Hassanein standards: in 24 (51%) babies the PI was less than 3rd centile. This suggests that, generally, LFD infants are underweight for length, and by inference, are likely to have experienced intrauterine undernutrition. In the first month the 24 'wasted' infants (PI less than 3rd centile) gained more rapidly in weight, and grew more quickly in head circumference and length than the 16 'nonwasted' infants (PI greater than 10th centile). Thereafter growth rates were similar. With the exception of weight in the 'nonwasted' infants during the first month, rates of growth (weight, length, and head circumference) in both groups of babies in each of the 3 months after birth were greater than in normal infants. The first 3 months after birth can therefore be defined as the period of 'catch-up' growth in LFD term infants.