Effect of an exercise rehabilitation program on physical function over 1 year in chronic kidney disease: an observational study.

BACKGROUND: Exercise rehabilitation may help maintain physical function in chronic kidney disease (CKD), but long-term clinical effectiveness is unknown. We evaluated the effect of an exercise rehabilitation program on physical function over 1 year in individuals with CKD. METHODS: This clinical program evaluation included adults with CKD (any stage) registered in a provincial renal program from 1 January 2011 to 31 March 2016. Attenders were referred to and attended a 10-week exercise rehabilitation program (n = 117). Nonattenders were referred, but did not attend the program (n = 133). Individuals enrolled in a longitudinal frailty study (n = 318) composed a second control group. Primary outcome: Change in physical function [short physical performance battery (SPPB) score]. Secondary outcomes included change in health-related quality of life, physical activity, exercise behaviour, hospitalization over 1 year. Predictors of improved SPPB were assessed using logistic regression. RESULTS: In sum, 53, 40 and 207 participants completed 1-year follow-up in attender, nonattender and second control groups, respectively. Baseline median SPPB [interquartile range (IQR)] scores were 10.5 (9-12), 10 (8-12) and 9 (7-11) in attender, nonattender and second control groups, respectively (P = 0.02). Mean change in SPPB score over 1 year was not significantly different between groups (P = 0.7). Attenders with baseline SPPB score <12, trended toward increased likelihood of improved SPPB score at 1 year [odds ratio (OR) 2.18; 95% confidence interval (CI) 0.95-5.02; P = 0.07]. More attenders (60%) exercised regularly at 1 year than nonattenders (35%) (P = 0.03). CONCLUSIONS: The impact of clinical exercise rehabilitation programs on physical function at 1 year needs further delineation. However, our observation of improved exercise behaviour at 1 year suggests sustained benefits with such programs in CKD.

Development of dilipid polymyxins: Investigation on the effect of hydrophobicity through its fatty acyl component.

Continuous development of new antibacterial agents is necessary to counter the problem of antimicrobial resistance. Polymyxins are considered as drugs of last resort to combat multidrug-resistant Gram-negative pathogens. Structural optimization of polymyxins requires an in-depth understanding of its structure and how it relates to its antibacterial activity. Herein, the effect of hydrophobicity was explored by adding a secondary fatty acyl component of varying length onto the polymyxin structure at the amine side-chain of l-diaminobutyric acid at position 1, resulting to the development of dilipid polymyxins. The incorporation of an additional lipid was found to confer polymyxin activity against Gram-positive bacteria, to which polymyxins are inherently inactive against. The dilipid polymyxins showed selective antibacterial activity against Pseudomonas aeruginosa. Moreover, dilipid polymyxin 1 that consists of four carbon-long aliphatic lipids displayed the ability to enhance the antibacterial potency of other antibiotics in combination against P. aeruginosa, resembling the adjuvant activity of the well-known outer membrane permeabilizer polymyxin B nonapeptide (PMBN). Interestingly, our data revealed that dilipid polymyxin 1 and PMBN are substrates for the MexAB-OprM efflux system, and therefore are affected by efflux. In contrast, dilipid polymyxin analogs that consist of longer lipids and colistin were not affected by efflux, suggesting that the lipid component of polymyxin plays an important role in resisting active efflux. Our work described herein provides an understanding to the polymyxin structure that may be used to usher the development of enhanced polymyxin analogs.