Risk factors and outcome measures in hand and knee osteoarthritis

The pathogenesis of OA is largely unknown; however, several risk factors are known to contribute to disease development. Treatment modalities are currently limited to alleviation of symptoms. In order to develop better treatment modalities, increase of the understanding of the underlying mechanisms leading to OA development may provide targets for disease modification. Furthermore, knowledge regarding appropriate outcome measures that can be applied in OA research has to be increased for adequate assessment of potential treatment effects. Therefore, part I of this thesis describes studies aiming to increase the understanding of mechanisms underlying the association between known risk factors and OA, especially focussing on obesity in relation to OA in weight-bearing and non-weight-bearing joints. Furthermore, it was investigated which specific structural abnormalities on specific locations within the knee joint could best discriminate presence of symptomatic OA, and impact of knee OA and its modifiable or preventable risk on health-related quality of life was evaluated. Part II of this thesis describes two systematic reviews, assessing available instruments for measurement of the domains pain, physical function, patient global assessment and imaging in hand OA in order to enable recommendations for use in clinical trials.Abbvie B.V., Chipsoft B.V., Pfizer B.V., Reumafonds, Stichting ArtrosezorgUBL - phd migration 201

Bioimpedance as a predictor of survival in renal failure and associated comorbidities.

Background: Renal failure requiring dialysis is associated with a high mortality. One of the contributing causes is overhydration. Overhydration can be assessed by bioimpedance analysis (BIA)– the non-invasive electrical measure of small current through the tissues that estimates the proportion of fluid that is intracellular water (ICW, typically muscle which is healthy) and extracellular (ECW, which in excess causes tissue oedema and is potentially dangerous). Several studies indicate that a extracellular water to total body water (TBW) ratio is associated with increased risk of death in dialysis patients but it is not clear if this is independent of other risk factors for death, namely comorbidity. Aims and objectives: To establish the prognostic value of BIA in the prediction of survival on dialysis in the context of other known predictors of survival or hospitalisation. With further analysis of the applicability of the same scenario to heart failure patients. Methodology: To conduct a systematic review using a standardised approach including a prespecified research question, search terms and criteria for study inclusion. With independent selection for inclusion in the study and quality appraisal by multiple authors with different backgrounds and experience. Results: 2701 studies identified by literature search, plus an additional 4 through reference checking. 38 papers included in final analysis, 4 of which were regarding heart failure cohorts. Analysis of the research shows that BIA is an independent predictor of mortality. Conclusion: BIA shown to be an independent predictor of mortality in dialysis patients, further research needed to extrapolate to heart failure (HF) populations

Biomedical Sensing and Imaging

This book mainly deals with recent advances in biomedical sensing and imaging. More recently, wearable/smart biosensors and devices, which facilitate diagnostics in a non-clinical setting, have become a hot topic. Combined with machine learning and artificial intelligence, they could revolutionize the biomedical diagnostic field. The aim of this book is to provide a research forum in biomedical sensing and imaging and extend the scientific frontier of this very important and significant biomedical endeavor

Resistance (exercise) training in non-dialysis dependent chronic kidney disease (ckd stage 3) and validation of ultrasound in the measurement of muscle size and structure in haemodialysis patients (ckd stage 5)

AIM: This thesis set out to make an original contribution to knowledge with regard to methods of assessing muscle size and architecture in the CKD and ESRD population, and to assess the ability to improve the muscle size and architecture, and symptoms of uraemia, by implementing an anabolic intervention (resistance exercise training) in the CKD population. OUTCOME MEASURES: Ultrasound was shown to have high validity (against gold standard MRI measures; ICCs: VLACSA 0.96, VL depth 0.99, fat depth 0.98) and intra-rater reliability (ICCs: VL depth 0.98, total muscle depth 0.97, fat depth 0.99; MDC: VL depth 0.14cm, total muscle depth 0.19cm, fat depth 0.22cm) in measuring regional body composition at the mid-VL site in the CKD population. There were significant (p<0.01) correlations between US-derived measures of (mid-VL) muscle size and architecture with strength and function (larger muscle mass and/or pennation angle positively correlated with higher strength and/or functional performance). Patient-reported uraemic symptoms were worse (p<0.01) in those with reduced strength and/or function. INTERVENTION RESULTS: An anabolic (resistance training) intervention (12-weeks, randomized to once [RT1 n=7] or three times [RT3 n=10] per week, 80%1RM) brought about significant improvements over time (p<0.01) in all measures of muscle size and architecture (VL depth, total muscle depth, VLACSA, pennation angle). Interaction effects (group*time) were only seen in pennation angle (p<0.05) and VLACSA (p<0.01) where RT3 gains were greater than RT1 from week 8 onwards. All measures of strength, function, and uraemic symptoms improved over time (p<0.01) with no interaction effects (no difference from greater training frequency/ volume). CLINICAL AND RESEARCH IMPLICATIONS: The intervention results suggest implementing a RT form of “prehabilitation” in early stage (CKD3) patients just once per week is sufficient to bring about statistically and clinically important changes in strength and function that benefit the patient through reduced frequency and/or intrusiveness of uraemic symptoms (improved health-related quality of life), with minimal time-commitment. Further research should examine if there is additional benefit to the significantly greater increases in VLACSA and pennation angle observed in RT3, with regards to long-term maintenance of functional improvements, and whether an RT1 or RT3 programme delays the progression of CKD, the need for RRT, and patient mortality.sub_phyunpub1807_ethesesunpu

Lifecourse influences on osteoarthritis of the knees, hips and hands as defined by musculoskeletal ultrasound

PhD ThesisAims: There has been very little lifecourse research looking at the risk of osteoarthritis (OA). A lifecourse analysis of risk factors for knee, hip and hand OA (defined using features on ultrasound) acting at different stages of life, including early life factors, was performed among members of the Newcastle Thousand Families birth cohort. Methods: Potential risk factors for OA (including birth weight, breast feeding data and socioeconomic status) have been collected prospectively in this birth cohort of subjects aged 63 (born in May-June 1947) and an a priori conceptual framework was developed. Subjects had both knees, hips and the dominant hand scanned with ultrasound. These data were analysed in relation to a range of factors from across the lifecourse using logistic and linear regression models. Results: Among 316 participants, duration of exclusive breast feeding showed a significant inverse association with knee osteophytes while BMI and total hip bone mineral density at age 50 increased the risk of knee osteophytes. The univariate effect of social class at birth on knee osteophytes was found to be mediated by its subsequent effect on breast feeding and total hip bone mineral density. The multivariate model for hip OA had three risk factors; BMI, physical activity and pack years of smoking at age 50. Smoking at age 50 and increased infections in childhood appeared to confer protection from hand OA. Conclusions: This is the first study to perform a lifecourse analysis of OA risk using prospectively collected data. The majority of the risk of OA at the three joint sites seemed to occur through factors acting in adulthood. However, breast feeding protected subjects from knee OA while infections in childhood decreased hand OA risk. These results suggest that modification of OA risk factors acting in adulthood would probably be more beneficial than intervening in early life.Northumbria Healthcare NHS Foundation Trus

Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and mortality. Radiotherapy-related cardiotoxicity is a heterogeneous clinical syndrome characterized by symptoms related to impaired cardiac function due to radiation-injury to one or more cardiac structures. Furthermore, the relative risk of CVD increases with increasing incidental radiation dose to the heart. There is not a unified consensus on the definition of CA-related cardiotoxicity although most trials have focused on changes in resting systolic function, and/or development of cardiac symptoms.Commonly used tools to assess cardiac function are insensitive to minor injury hence subtle changes may go unnoticed for many years. Cardiotoxicity definitions should include a dynamic functional assessment of the CV system. This may allow detection of latent CV abnormalities before the precipitous decline of resting myocardial function or the development of CV symptomology that may impact quality of life. Cardiopulmonary exercise testing (CPET) including measurement of peak oxygen consumption (VO2) is the gold standard for the assessment of cardiorespiratory fitness (CRF). Cardiorespiratory fitness is a strong, independent predictor of mortality, CVD-related mortality, HF-related morbidity and mortality, CA-related mortality and may be involved in the pathophysiologic link between anti-CA related treatments and the increased risk of late CVD events. Emerging evidence indicates CRF may be reduced in CA survivors and have utility to detect subclinical cardiotoxicity, but this has not been evaluated in CA survivors treated with RT with significant heart involvement. This dissertation consists of one literature review and one comprehensive paper that will examine the ability of CPET to detect subclinical cardiotoxicity

Body composition changes over three years in older adults: a descriptive longitudinal analysis

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2016 do Instituto Politécnico de Lisboa. Código de referência: IPL/2016/SFQ2017_ESTeSLIntroduction: Many studies analyze body composition changes in older adults. However, few studies analyze body composition in elderly people with functional measures. Studies using Double X-Ray analysis (DXA) or Bioimpedance analysis proved to be reliable but expensive or only possible in a laboratory environment. The purpose of our study was to analyze changes in body composition over three years using anthropometric measures in a sample of elderly people in order to perceive functional changes. Methods: Forty-three participants (12 men; 31 women) aged 60 years and over and independent in activities of daily life were assessed using anthropometric measures in the first moment and past three years. Weight, height, waist and hip circumference were measured, and body mass index (BMI) and waist-to-hip ratio (WHR) were also calculated. Skeletal muscle mass (SMM) was also calculated using Al-Gindan et al. (2014) equations and normalized for height to found skeletal muscle index (SMI) in order to analyze cut-off points associated with physical disability according to Janssen et al (2004). Results: A significant difference was found over three years in SMM (p = 0.007), SMI (p = 0.027), BMI (p = 0.041) and WHR (p = 0.003). The majority of the participants has decreased SMM, SMI, and BMI and increased WHR, which favors a worst prognostic for comorbidities associated with these variables, and a tendency for sarcopenic obesity seems to be present although more studies are needed. Also, we found that using cut-off points for disability risk 83.3% of the men and 38.7% of the women of our sample were at moderate or high risk of disability. Three years later this percentage has increased but only for women to 54.8%. Conclusions: Although men are at risk of disability, women quickly lose their functional capacity, making necessary a rapid intervention to reduce the risk of disability in this population.info:eu-repo/semantics/publishedVersio