Relative Contributions of Lean and Fat Mass to Bone Mineral Density: Insight From Prader-Willi Syndrome

Context: Low bone mineral density (BMD) is the most important risk factor for fragility fracture. Body weight is a simple screening predictor of difference in BMD between individuals. However, it is not clear which component of body weight, lean (LM), or fat mass (FM), is associated with BMD. People with the genetic disorder of Prader-Willi syndrome (PWS) uniquely have a reduced LM despite increased FM.Objective: We sought to define the individual impact of LM and FM on BMD by investigating subjects with and without PWS.Design, Setting and Participants: This cross-sectional study was conducted at the Clinical Research Facility of the Garvan Institute of Medical Research, with PWS and control participants recruited from a specialized PWS clinic and from the general public by advertisement, respectively. The study involved 11 adults with PWS, who were age- and sex-matched with 12 obese individuals (Obese group) and 10 lean individuals (Lean group).Main Outcome Measures: Whole body BMD was measured by dual-energy X-ray absorptiometry. Total body FM and LM were derived from the whole body scan. Differences in BMD between groups were assessed by the analysis of covariance model, taking into account the effects of LM and FM.Results: The PWS group had significantly shorter height than the lean and obese groups. As expected, there was no significant difference in FM between the Obese and PWS group, and no significant difference in LM between the Lean and PWS group. However, obese individuals had greater LM than lean individuals. BMD in lean individuals was significantly lower than in PWS individuals (1.13 g/cm2 vs. 1.21 g/cm2, p < 0.05) and obese individuals (1.13 g/cm2 vs. 1.25 g/cm2, p < 0.05). After adjusting for both LM and FM, there was no significant difference in BMD between groups, and the only significant predictor of BMD was LM.Conclusions: These data from the human genetic model Prader-Willi syndrome suggest that LM is a stronger determinant of BMD than fat mass

Influence of naltrexone/bupropion combination treatment on body mass index in Prader-Willi Syndrome Re: 'Prader-Willi Syndrome, management of impulsivity, and hyperphagia in an adolescent' by Puri et al. (J Child Adolesc Psychopharmacol 26:403-404)

We read with interest the case report by Puri et al. (2016) describing a 13-year-old girl with Prader–Willi syndrome (PWS) treated for 6 weeks with a naltrexone/bupropion combination (Contrave) to target impulsivity, inattention, physical aggression, and overeating behavior (Puri et al. 2016)..

Genetic, endocrine, metabolic, immune and autonomic influences on energy homeostasis and cardiovascular risk in Prader-Willi syndrome

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity, caused by the loss of expression of an imprinted region on chromosome 15. PWS is characterised by muscular hypotonia and failure to thrive during infancy, followed by the development of hyperphagia. This has an onset at approximately 2-6 years and persists throughout life, and currently has no effective pharmaceutical treatment. Other features of the syndrome include short stature, hypogonadism, hypopigmentation, developmental delay and behavioural problems. A number of co-morbidities of PWS, including cardiopulmonary disease, type 2 diabetes and thrombophlebitis, are secondary to obesity. This project aimed to characterise the nature of the appetite dysregulation in PWS and to determine its association with endocrine, metabolic, immune and autonomic influences. In order to do this, we recruited a group of adults with PWS, matched obese controls and lean controls and conducted a meal study. Assessment of appetite and appetite-regulating hormones identified a defect in the postprandial hunger response (driven by elevated ghrelin), but not in the satiety response in PWS. Indirect calorimetry did not detect alterations in meal metabolism in PWS. Analysis of heart rate variability revealed that the PWS cohort had reduced sympathetic autonomic responsiveness compared to controls, which may be related to increased cardiovascular risk. Assessment of immune function showed that the PWS group had similar levels of low-grade inflammation to the obese group with the exception of IL-6, which was elevated. A second arm of the project investigated the role of Snord116, a snoRNA gene cluster implicated in the genetic aetiology of PWS. In order to do this, we assessed the metabolic effects of the deletion of Snord116 in mice at two different time points: in the germline and in adult mice. We found a critical role for Snord116 in the regulation of growth and food intake, with each model mimicking a different nutritional stage of PWS. In conclusion, this project found that the mechanisms behind appetite dysregulation and cardiovascular risk in PWS have a complex and interdependent basis, and identified potential roles for ghrelin, sympathetic nervous system activity, IL-6 and Snord116 in future pharmaceutical treatments of PWS hyperphagia

A cross-sectional study exploring cognitive impairment in kidney failure

Background: Little is known of the prevalence or associated factors of cognitive impairment in people with kidney failure. Assessment of cognition is necessary to inform comprehension of healthcare information, aptitude for dialysis modality and informed decision making. Objectives: This study sought to determine the prevalence and factors associated with cognitive impairment in people with kidney failure. Design: Prospective cross-sectional. Participants: Participants (n = 222) with chronic kidney disease grade 5 (CKD G5) including those not treated with dialysis, those undertaking dialysis independently or in a facility (CKD 5D), and those with a kidney transplant (CKD 5T). Measurements: Data were collected using the Montreal Cognitive Assessment tool, the Hospital Anxiety and Depression Scale (only the depression subscale), and a demographic questionnaire. Type of kidney disease and comorbidities were extracted from participants' hospital records. Results: Participants were 61 ± 13.63 years old; most were male (61.26%), and diabetes was the primary cause of kidney disease (34%). Prevalence of cognitive impairment was 34% although it was significantly higher for those in CKD G5 compared with other groups. A number of factors were found to be associated with cognitive impairment including, age, diabetes, hypertension, education, haemoglobin, albumin, parathyroid hormone, CKD G5, and length of time on treatment. Conclusions: Cognitive impairment in kidney failure is common and it has significant implications for informed decision making and treatment choices. Routine assessment of cognitive function is an important part of clinical practice.</p

Factors influencing health-related quality of life in people with chronic kidney disease : A structural equation modelling approach

AIMS AND OBJECTIVES: To test whether the revised Wilson and Cleary model could identify which factors contribute to health-related quality of life in chronic kidney disease.BACKGROUND: Chronic kidney disease affects a person's health-related quality of life detrimentally although nursing practice informed by theory is only beginning to emerge.DESIGN: A cross-sectional study reported using the STROBE guidelines.METHODS: About 886 participants with chronic kidney disease (varying grades) completed validated measures of symptoms (renal version of the Integrated Palliative care Outcome Scale), and general health perceptions and health-related quality of life (European Quality of Life five-dimension three-level). Socio-demographic and renal characteristics were also collected. Data were analysed using descriptive statistics and structural equation modelling.RESULTS: Biological function (decreased kidney function and haemoglobin and greater number of comorbidities), directly contributed to increased symptom burden. Symptoms demonstrated strong negative relationships with both general health perceptions and health-related quality of life. General health perceptions had a direct positive relationship with health-related quality of life. As age increased, health-related quality of life decreased. The only environmental characteristic of significance was the distance between home and hospital although it was not directly associated with health-related quality of life. Overall, the model explained approximately half of the deterioration in health-related quality of life.CONCLUSIONS: The model demonstrated how various factors influence alteration of health-related quality of life in people with chronic kidney disease. Early identification of these factors could assist nurses to introduce effective management strategies into patient care plans proactively.RELEVANCE TO CLINICAL PRACTICE: Comprehensive symptom assessment needs to occur not only in kidney failure but in earlier chronic kidney disease grades to enable timely interventions targeted at improving people's wellbeing.PATIENT OR PUBLIC CONTRIBUTION: Validated interviewer administered questionnaires were completed by participants with chronic kidney disease in this study.</p

The relationship between chronic kidney disease, symptoms and health-related quality of life: A systematic review

Background People with chronic kidney disease (CKD) experience a wide range of symptoms due to reduced kidney function. As the disease progresses these symptoms become more burdensome and often negatively affect a person’s health‐related quality of life (HRQoL).Objective To examine the evidence of symptoms and HRQoL in CKD stages 1–5 and the relationships between these.Methods Studies published in English from January 2008 to July 2018 using six databases (PubMed, MEDLINE, CINAHL, PsycINFO, Cochrane Library and JBI Library) were searched.Results Thirteen studies were included in this review although only three had interventional designs. By considering symptom experience and HRQoL together, four studies found that HRQoL decreased when symptoms increased. Feeling washed out, fatigue and drowsiness were found to be the most common symptoms reported. Only two studies reported follow‐up measurements although six studied how symptoms change over time. None of the studies examined the change of symptoms over time across the different CKD stages. The majority of studies showed a decline in physical HRQoL and improvement in mental HRQoL over time. Nutritional and exercise interventions showed some improvements in symptom experience and HRQoL.Conclusions Only four studies were found that reported the relationship between symptoms and HRQoL of those with CKD. Of these, in view of symptom experience and HRQoL together, HRQoL decreased when symptoms increased. However, more research is warranted to establish a clear understanding of the relationship between symptoms and HRQoL in CKD to enable the design of appropriate interventions

Impact of chronic kidney disease on everyday life: A descriptive qualitative study

BACKGROUND: Living with chronic kidney disease is stressful as the disease and its treatments impact on everyday physical, psychological, and social activities. As this disease has a long trajectory, it is important to understand everyday life experiences of those at different points along this trajectory.OBJECTIVES: To explore the impact of chronic kidney disease and its treatment on everyday life.DESIGN: Descriptive qualitative design PARTICIPANTS: Twenty-five adults with chronic kidney disease across various grades were purposively recruited.APPROACH: Data were collected using semistructured interviews. Deductive content analysis informed by the revised Wilson and Cleary model was used to analyse data.FINDINGS: There were four themes. Theme 1, experiencing deterioration of kidney function, reflected the physical and psychological problems experienced by participants. Theme 2, changes that happened to me and my family, explained the subsequent limitations in their physical, social and role functioning. Theme 3, responding to a new normal, identified adjustments needed in everyday life to cope with the disease and its treatments. The final theme, thinking ahead and making a decision, captured the future plans and decisions needed while living with chronic kidney disease.CONCLUSIONS: People with chronic kidney disease experience complex challenges such as greater symptom burden and functional limitations across the disease grades which impact on their everyday life. Nurses' recognition of these challenges is crucial for identifying and addressing unmet needs. Early individualised interventions, such as routine symptom assessment and management strategies that improve the wellbeing of people are needed.</p

Alterations in symptoms and health-related quality of life as kidney function deteriorates: A cross-sectional study

Aims and objectives: To compare symptoms and health-related quality of life and to examine the relationship between these as kidney function deteriorates. Background: Chronic kidney disease is a global health problem, and while knowledge of symptom burden and health-related quality of life is understood in kidney failure (previously end-stage kidney disease), there is limited understanding about symptoms and health-related quality of life across the chronic kidney disease trajectory. Design: Cross-sectional design reported using the STROBE guidelines. Methods: Eight hundred eighty-six adults with varying levels of kidney function (chronic kidney disease grades 3b–5 including those receiving dialysis) completed the renal version of the Integrated Palliative care Outcome Scale and the Quality of Life Short Form-36 version 2. Socio-demographic and renal characteristics were also collected. Data were analysed using descriptive and inferential statistics. Results: Participants had a mean age of 57 years and were mostly male. Regardless of chronic kidney disease grade, pain, poor mobility, weakness, anxiety and depression were the most prevalent and severe symptoms reported. Health-related quality of life was significantly associated with physical and psychological symptom scores. As kidney function deteriorated, both physical and mental health-related quality of life decreased, and prevalence and severity of symptoms increased. Conclusions: There is substantial symptom burden irrespective of chronic kidney disease grade, which overwhelmingly affects health-related quality of life. Early identification by nurses would enable proactive management plans to be implemented. Relevance to clinical practice: Nurses, whether in specialist renal services or in primary healthcare, are ideally placed to regularly assess symptoms and health-related quality of life in those with chronic kidney disease. Timely assessment could assist in the targeting of earlier interventions designed to reduce symptom burden and to increase health-related quality of life.</p