The effects of exercise and active assisted cycle ergometry in post-operative total knee arthroplasty patients - a randomized controlled trial.

PURPOSE: The purpose of this study was to examine the effect of the use of an active assisted cycle ergometer as an adjunct to post-operative treatment following total knee arthroplasty. METHOD: A total of 55 participants aged 50-80 years who had undergone unilateral total knee arthroplasty were randomly assigned to either the control group (standard of care) or the active assisted cycle ergometer (AACE) group. The effect on patient motivation, blood biomarkers, and knee pain, function, range of motion (ROM), strength, and swelling was examined. Qualitative feedback was also obtained post-operatively. RESULTS: Although there was no statistically significant difference in the standard of care compared to the AACE group, there was a trend for a greater reduction in knee pain on the visual analog scale, improved Lower Extremity Functional Scale scores, and knee extension ROM and strength. A greater percentage of the experimental group demonstrated higher motivation. There was no significant difference in swelling or blood biomarker measures. Qualitative feedback from the AACE group post-operatively was also positive. CONCLUSIONS: The use of an AACE protocol as an adjunct to total knee arthroplasty rehabilitation may improve post-operative clinical outcomes. This study has been registered at clinicaltrials.gov (identifier NCT02265523 , Oct 16 2014). LEVEL OF EVIDENCE: Level 1 - randomized controlled trial. Further research with a larger sample size is needed to confirm the benefits of the ergometer use.

Dietary protein and beef consumption predict for markers of muscle mass and nutrition status in older adults.

OBJECTIVE: To determine the relationship of beef and protein intake to nutrition status, body composition, strength, and biochemical measures of vitamin and mineral status, inflammation and blood lipids in older adults. DESIGN: Cross-sectional observational study. SETTING: State of Ohio, U.S.A. PARTICIPANTS: 142 adults ages 60-88. MEASUREMENTS: Subjects completed a Diet History Questionnaire, and questionnaires related to nutrition status and activity. Subjects also underwent measurements of body composition and strength, and a subset took part in a blood draw for biochemical measurements. RESULTS: Beef intake (g/d) was positively correlated to muscle mass measured by mid-arm muscle area (R=0.128, p=0.030). From multiple linear regression analysis, a 1oz/d (~28g/d) increase in beef consumption predicts for a 2.3cm(2) increase in mid-arm muscle area. Beef intake was negatively correlated to total (R=-0.179, p=0.035) and HDL (R=-0.247, p=0.004) cholesterol, and there was no association between beef and LDL-cholesterol, triglycerides, liver enzymes, or inflammatory markers. Protein intake (% of total energy) was positively correlated to nutrition status measured by the Mini Nutrition Assessment (R=0.196, p=0.020), and calf circumference (R=0.190, p=0.024), and these correlations remained when potential confounders were accounted for in multiple linear regression models. Protein intake was also positively correlated with BMI when analyzed with multiple linear regression. CONCLUSIONS: Beef intake was positively associated with mid-arm muscle area, and protein intake was positively associated with nutrition status, calf circumference, and BMI in older adults. Consuming lean cuts of beef in moderation may be a healthy way in which older adults can increase protein intake, preserve muscle mass and improve nutrition status.

Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians.

The ability to metabolize CYP2D6 substrates sparteine, debrisoquine, and dextromethorphan was studied in healthy Caucasian (n = 20), Ghanaian (n = 21), and Chinese (n = 22) CYP2D6 extensive metabolizers. Genotype analysis for the CYP2D6*1, *3, *4, *5, *9, *10, and *17 alleles was performed. Interethnic differences in the disposition of the probe drugs were found among the extensive metabolizers; extensive metabolizer status was confirmed by phenotype and genotype analysis. The mean metabolic rate was lower for Caucasians than for Ghanaians for sparteine (P < 0.02) and for both Ghanaians and Chinese for debrisoquine (P < 0.02). Correlation comparisons resulted in lower pairwise correlation coefficients in Ghanaians compared with Chinese and Caucasians for every combination of probe substrates. In addition, in Chinese and Caucasians, metabolic rates for each pair of probe drugs were significantly correlated (P < 0.002), but in Ghanaians the dextromethorphan metabolic rates were not correlated to either sparteine or debrisoquine (P < 0.05). Even when only those with a CYP2D6*1/*1 genotype were included in the correlation calculations, the Ghanaians had very low correlation coefficients (r(s) - 0.02-0.2, n = 9); much lower than those found in Caucasian (r(s) 0.78-0.92, n = 14) or Chinese (r(s) 0.54-0.96, n = 7) individuals. Quinidine had significantly less affect on sparteine metabolic rates in Ghanaians than both Caucasians and Chinese (P < 0.02). In addition, five of the 21 Ghanaian individuals had dextromethorphan metabolic ratios which were unaffected by quinidine. These individuals also had differences in urinary recovery of dextromethorphan and its metabolites when compared to the other Ghanaian individuals. These results confirm the large ethnic differences in probe drug metabolism and quinidine sensitivity among these ethnic groups. They also suggest that the Ghanaians have an additional unidentified allele(s) with altered substrate specificity and quinidine sensitivity which is currently genotyped as CYP2D6*1.

Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence.

Oral opiates (e.g. codeine, oxycodone, and hydrocodone) are metabolized by cytochrome CYP2D6 to metabolites of increased activity (e.g. morphine, oxymorphone and hydromorphone). CYP2D6 is genetically polymorphic, 4-10% of Caucasians lack CYP2D6 activity (poor metabolizers) due to inheritance of two non-functional alleles. We tested whether the failure to activate oral opiates was a protection factor in opiate dependence by genotyping (CYP2D6*3 and CYP2D6*4 defective mutant alleles) caucasians who met or didn't meet DSM criteria for oral opiate dependence. In opiate (+/- smoking) dependent subjects we found no poor metabolizers. In contrast, the poor metabolizer frequency in never-dependent control and multi-drug dependent comparison groups was 4% and 6.5%, respectively. This under-representation of poor metabolizers (Fisher's exact test, p < or = 0.05) in people dependent on oral opiates suggests that the CYP2D6 defective genotype is a pharmacogenetic protection factor for oral opiate dependence (estimated odds ratio > 7). This is the first investigation and demonstration of differences in genetically determined P450 metabolism influencing risk for substance dependence and we suggest that these differences may influence the risk for dependence of other substrate drugs, and may occur with other genetically variable P450s.