Purpose of Review Biological age is the concept of using biophysiological measures to more accurately determine an individual's age-related risk of adverse outcomes. Grading of the degree of frailty and measuring biomarkers are distinct methods of measuring biological age. This review compares these strategies for estimating biological age for clinical purposes. Recent Findings The degree of frailty predicts susceptibility to adverse outcomes independently of chronological age. The utility of this approach has been demonstrated across a range of clinical contexts. Biomarkers from various levels of the biological aging process are improving in accuracy, with the potential to identify aberrant aging trajectories before the onset of clinically manifest frailty. Summary Grading of frailty is a demonstrably, clinically, and research-relevant proxy estimate of biological age. Emerging biomarkers can supplement this approach by identifying accelerated aging before it is clinically apparent. Some biomarkers may even offer a means by which interventions to reduce the rate of aging can be developed.

Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase‐2 (MMP‐2). It has been shown that simultaneous inhibition of MMP‐2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML‐7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co‐administration of nitric oxide synthase (NOS) inhibitor (1400W or L‐NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia–reoxygenation (H‐R)‐induced contractile dysfunction of cardiomyocytes. Isolated cardiomyocytes were subjected to 3 min. of hypoxia and 20 min. of reoxygenation in the presence or absence of the inhibitor cocktails. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP‐2 by Doxy (25–100 μM), MLCK by ML‐7 (0.5–5 μM) and NOS by L‐NAME (25–100 μM) or 1400W (25–100 μM) protected myocyte contractility after H‐R in a concentration‐dependent manner. Inhibition of these activities resulted in full recovery of cardiomyocyte contractility after H‐R at the level of highest single‐drug concentration. The combination of subthreshold concentrations of NOS, MMP‐2 and MLCK inhibitors fully protected cardiomyocyte contractility and MLC1 from degradation by MMP‐2. The observed protection with addition of L‐NAME or 1400W was better than previously reported combination of ML‐7 and Doxy. The results of this study suggest that addition of NOS inhibitor to the mixture of inhibitors is better strategy for protecting cardiomyocyte contractility.

Background: Peritoneal dialysis (PD) is an underutilized, therapeutic option to in-center hemodialysis (HD), given its similar survival and clinical efficacy but provides lifestyle benefits and cost savings. Despite these advantages, PD prevalence rates remains below 20% in many Canadian jurisdictions. Objectives: The primary objective of this study was to identify and assess patient-perceived barriers to PD implementation in Saskatchewan. The secondary objectives were to examine variations in patient-perceived barriers to PD by dialysis units (main dialysis units vs satellite dialysis units) and specific challenges faced by First Nation patients residing on reserves. Design: A cross-sectional observational survey study. Setting: Two major centers (Regina and Saskatoon) and 5 associated satellite units attached to each center across the province of Saskatchewan. Patients: We approached all prevalent in-center HD patients across Saskatchewan, 366 (49%) agreed to participate in the study. Measurements: Self-reported barriers to PD were assessed using a 26-question survey which was created after engagement of our multidisciplinary team. Methods: We conducted a cross-sectional survey of 740 prevalent in-center HD patients within the province of Saskatchewan, Canada, from June 2018 to January 2019. Around 366 (49%) patients agreed to participate in the study. The questionnaire was designed to capture patients’ perceived barriers to PD. Descriptive statistics were used to present the data. Chi-square and Mann-Whitney U-test were used to compare the patients’ responses (main dialysis units vs satellite dialysis units, and First Nation reserves vs nonreserves). Results: Of the 366 patients who completed the survey, 284 met the eligibility criteria and were included in the analysis. Patient-reported satisfaction with current in-center HD care was the most common barrier to PD uptake (92%), followed by proximity to their HD unit (61%). A lack of understanding of the benefits/risks of PD, fear of family burden (54% each), and unwillingness to dialyze daily and to learn a new technique (51% each) were additional factors. Patients residing on reserves compared to nonreserve residents felt PD had a higher risk of infection compared to HD (54% vs 34%, P = .005), and felt PD led to suboptimal care (47% vs 31%, P = .021). Limitations: We used a nonstandardized locally derived questionnaire to quantify barriers, and this prevents inclusion of additional barriers than individual patients may consider important. Cross-sectional data can only be used as a snapshot. Only 366 patients agreed to participate, and the results cannot be generalized to 740 prevalent HD patients. We did not capture data on demographics (age, income, and literacy level), comorbidities, and dialysis vintage, which would have been helpful in interpretation of the results. We did not involve patients, carers, or patients of First Nations heritage, in the design of the survey and the study. Conclusions: The results of our survey indicate that the major patient-reported barrier to PD uptake in our province is clinical inertia in patients defaulted to in-center HD at the onset of dialysis. Lack of patient awareness and knowledge of PD as a viable treatment modality also figured prominently, as did fears/concerns surrounding the safety, efficacy, and perceived family burden with PD compared with in-center HD. Trial Registration: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Background: Despite clinical and lifestyle advantages of home hemodialysis (HHD) compared with in-center hemodialysis (ICHD), it remains underutilized in our province. The aim of the study was to explore the patients’ perception and to identify the barriers to use of HHD in Saskatchewan, Canada. Objectives: The primary objective of the study was to evaluate and explore patient perceptions of HHD and to identify the obstacles for adoption of HHD in Saskatchewan. The secondary objective was to examine variations in the patients’ perceptions and barriers to HHD by center (main dialysis units vs satellite dialysis units). Design: This is a cross-sectional observational survey study. Setting: Two major centers (Regina and Saskatoon) and 5 associated satellite units attached to each center across the province of Saskatchewan. Patients: We approached all prevalent ICHD patients across Saskatchewan, 398 agreed to participate in the study. Measurements: Self-reported barriers to HHD were assessed using a questionnaire. Methods: A questionnaire was designed to determine the patients’ perceived barriers to HHD. Descriptive statistics was used to present the data. Chi-square and Mann-Whitney U test were used to compare the patients’ responses between main and satellite units Results: Satisfaction with current dialysis care (91%), increase in utility bills (65%), fear of catastrophic events at home (59%), medicalization of one’s home (54%), and knowledge deficits toward treatment modalities (54%) were the main barriers to HHD uptake. Compared with patients dialyzing in our main units, satellite patients chose not to pursue HHD more frequently because they had greater satisfaction with their current dialysis unit care (97% vs 87%, P < .001), felt more comfortable dialyzing under the supervision of medical staff (95% vs 86%, P < .007), could not afford additional utility costs (92% vs 45%, P < .001), were unaware of the risks and benefits of HHD (83% vs 33%, P < .001), had concerns over time commitments for training to HHD (69% vs 32%, P < .001), and had concern for family burnout (60.8% vs 40.6%, P < .001). Limitations: We used questionnaires to quantify known barriers, and this prevents inclusion of additional barriers that individual patients may consider important. Cross-sectional data can only be used as a snapshot. Only 398 patients agreed to participate, and the results cannot be generalized to 740 prevalent HD patients. We did not capture data on demographics (age, income, and literacy level), comorbidities, and dialysis vintage, which would have been helpful in interpretation of the results. Conclusions: Satisfaction with in-center care, lack of awareness and education, specifically in the satellite population, concerns with family burnout, expenses associated with utilities, and training time will need to be addressed to increase the uptake of HHD. Trial Registration: The study was not registered on a publicly accessible registry as it did not involve any health care intervention on human participants.