The objective of this study was to determine the feasibility and efficacy of an exercise training program to improve exercise capacity and fatigue level in pediatric patients with end-stage renal disease (ESRD). Twenty children on dialysis intended to perform a 12-week graded community-based exercise program. Exercise capacity and fatigue level were studied; muscle force and health-related quality of life were secondary outcomes. All outcomes were measured at baseline (T = 0) and after intervention (T = 1). Fourteen of the 20 patients (70%) either did not start the program or did not complete the program. Of these patients, seven did not complete or even start the exercise program because of a combination of lack of time and motivational problems. Six patients were not able to continue the program or were unable to do the follow-up measurements because of medical problems. Exercise capacity and muscle strength was higher after the exercise program in the children who completed the training. In conclusion, exercise training is difficult to perform in children with ESRD and is not always feasible in real-life situations for many children with ESRD.
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End-stage kidney disease patients treated with conventional hemodialysis (CHD) are known to have impaired physical performance and protein-energy wasting (PEW). Nocturnal hemodialysis (NHD) was shown to improve clinical outcomes, but the evidence is limited on physical performance and PEW. We investigate whether NHD improves physical performance and PEW. This prospective, multicenter, non-randomized cohort study compared patients who changed from CHD (2-4 times/week 3-5 h) to NHD (2-3 times/week 7-8 h), with patients who continued CHD. The primary outcome was physical performance at 3, 6 and 12 months, assessed with the short physical performance battery (SPPB). Secondary outcomes were a 6-minute walk test (6MWT), physical activity monitor, handgrip muscle strength, KDQOL-SF physical component score (PCS) and LAPAQ physical activity questionnaire. PEW was assessed with a dietary record, dual-energy X-ray absorptiometry, bioelectrical impedance spectroscopy and subjective global assessment (SGA). Linear mixed models were used to analyze the differences between groups. This study included 33 patients on CHD and 32 who converted to NHD (mean age 55 ± 15.3). No significant difference was found in the SPPB after 1-year of NHD compared to CHD (+0.24, [95% confidence interval -0.51 to 0.99], p = 0.53). Scores of 6MWT, PCS and SGA improved (+54.3 [95%CI 7.78 to 100.8], p = 0.02; +5.61 [-0.51 to 10.7], p = 0.03; +0.71 [0.36 to 1.05], p < 0.001; resp.) in NHD patients, no changes were found in other parameters. We conclude that NHD patients did not experience an improved SPPB score compared to CHD patients; they did obtain an improved walking distance and self-reported PCS as well as SGA after 1-year of NHD, which might be related to the younger age of these patients.
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Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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Intradialytic hypotension (IDH) is considered to be a frequent complication of hemodialysis (HD) and is associated with symptom burden, increased incidence of access failure, cardiovascular events, and higher mortality. This systematic literature review aims to analyse studies that investigated the prevalence of IDH. A complicating factor herein is that many different definitions of IDH are used in literature.Methods: A systematic literature search from databases, Medline, Cinahl, EMBASE, and the Cochrane library to identify studies reporting on the actual prevalence of IDH was conducted. Studies were categorized by the type of definition used for the prevalence of IDH. A meta-analysis of the prevalence of IDH was performed.Results: In a meta-analysis comprising 4 studies including 1,694 patients and 4 studies including 13,189 patients, the prevalence of HD sessions complicated by IDH was 10.1 and 11.6% for the European Best Practice Guideline (EBPG) definition and the Nadir <90 definition, respectively. The proportion of patients with frequent IDH could not reliably be established because of the wide range in cutoff values that were used to identify patients with frequent IDH. There was a large variety in the prevalence of symptoms and interventions. Major risk factors associated with IDH across studies were diabetes, a higher interdialytic weight gain, female gender, and lower body weight.Conclusion: Our meta-analysis suggests that the prevalence of IDH is lower than 12% for both the EBPG and the Nadir <90 definition which is much lower than stated in most reviews.
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BackgroundCritically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets.MethodsThe PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models.DiscussionThe PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04633421. Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.
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Abstract: Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.
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Objective: Patients with chronic limb threatening ischemia (CLTI) are at high risk for amputation and other cardiovascular adverse events. Nutrition-related symptoms and malnutrition are common in the CLTI population, and lead to worse clinical outcomes. Understanding of the factors influencing nutritional intake is required to determine whether optimization of nutritional intake in this population requires interventions. Therefore, this study aimed to describe perceptions and experiences on nutrition of patients with CLTI, and to identify perceived barriers and facilitators influencing their nutritional intake.Methods: In this phenomenological qualitative study, individual semi-structured, face-to-face interviews were conducted with patients with CLTI who lived independently. Interviews were transcribed verbatim, and reflexive thematic analysis was performed.Results: Twelve participants were interviewed. Five themes were generated: (1) lack of nutritional risk perception, (2) role of nutrition for health, functioning and surviving, (3) multiple factors influencing nutritional intake, (4) limited nutritional advice, and (5) no intention to change current nutritional intake.Conclusion: Patients with CLTI perceive nutritional intake as a necessity to survive and function. Patients express limited risk perception regarding adequate nutritional intake and undernutrition. Nutritional intake is mainly based on non-health related factors, as habits and taste, and multiple barriers hinder nutritional intake. Patients received no or only limited nutritional advice. Together this leads to an expressed lack of intention to change nutritional intake. Findings of this study stress the urgency for patient-centered nutritional support, to increase nutrition-related knowledge and motivation, to prevent or treat undernutrition, and may improve clinical outcomes in patients with CLTI.
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Abstract Purpose To determine the predictive value of quality of life for mortality at the domain and item levels. Methods This longitudinal study was carried out in a sample of 479 Dutch people aged 75 years or older living independently, using a follow-up of 7 years. Participants completed a self-report questionnaire. Quality of life was assessed with the WHOQOL-BREF, including four domains: physical health, psychological, social relationships, and environment. The municipality of Roosendaal (a town in the Netherlands) indicated the dates of death of the individuals. Results Based on mean, all quality of life domains predicted mortality adjusted for gender, age, marital status, education, and income. The hazard ratios ranged from 0.811 (psychological) to 0.933 (social relationships). The areas under the curve (AUCs) of the four domains were 0.730 (physical health), 0.723 (psychological), 0.693 (social relationships), and 0.700 (environment). In all quality of life domains, at least one item predicted mortality (adjusted). Conclusion Our study showed that all four quality of life domains belonging to the WHOQOL-BREF predict mortality in a sample of Dutch community-dwelling older people using a follow-up period of 7 years. Two AUCs were above threshold (psychological, physical health). The findings offer health care and welfare professionals evidence for conducting interventions to reduce the risk of premature death.
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BACKGROUND: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS).METHODS: We analyzed data from the multicenter observational 'PRactice of VENTilation in COVID-19 patients' study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed.RESULTS: Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27-7.72 L), 0.78 L (0.26-1.27 L), and - 0.35 L (- 6.52-0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77-0.95, P = 0.0047). Sensitivity analyses showed similar results.CONCLUSIONS: In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020.
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