Saudi Cultural Missions Theses & Dissertations
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Item Restricted PROTEIN NUTRITION IN PAEDIATRIC CROHN’S DISEASE(University of Nottingham, 2024) Aljilani, Bayan; Moran, Gordon; Tsintzas, KostasAltered nutritional status is well documented in Crohn’s disease patients, which may lead to low muscle mass and deteriorated function (sarcopenia) and adverse disease outcomes. Although a variety of experimental methods have assessed muscle mass and function in paediatric CD patients, there is no conclusive consensus on the definition of sarcopenia in those patients. However, most of the studies in the literature have showed reduction in muscle mass (MM), lean mass (LM) and fat-free mass (FFM) in paediatric CD compared with healthy controls or reference data. Historically, underweight was frequently linked with paediatric CD. However, recent evidence suggests a shift towards adiposity rather than underweight being prevalent in paediatric CD. Our knowledge of the relationship between adiposity and adverse disease outcomes in children with CD is limited. In addition, clinical characteristics of CD patients may vary depending on age at diagnosis. Moreover, adult CD patients exhibit altered nutritional status and eating behaviour that impact negatively on habitual dietary protein intake, protein metabolism and muscle mass. However, these relationships have never been investigated in paediatric CD. This PhD thesis used the gold standard technique, magnetic resonance imaging (MRI), to assess leg muscle volume in children with stable CD disease and compared it with matched healthy subjects. These findings were linked with dietary protein intake, fasting plasma amino acids (AAs) and eating behaviour traits. In addition, the MRI technique was used to compare psoas muscle cross sectional area (PCSA) between paediatric with active CD versus those with inactive CD. However, conclusive findings were limited due to small sample size in both studies. This thesis highlighted the need for standardisation of body composition and sarcopenia terminology, as well as the valid use of assessment tools in adequately powered populations with appropriately matched comparators, to establish a clear definition of sarcopenia and assess its prevalence in paediatric IBD. In addition, it revealed that adiposity is linked to poor clinical outcomes in a long-term follow-up cohort of paediatric-onset CD, and that the age at disease onset is also associated with negative clinical outcomes. Moreover, this thesis revealed comparable dietary protein and energy intake, and eating behaviour traits between stable CD paediatric patients and matched healthy controls, which may explain the lack of differences in leg muscle volume and handgrip strength (indices of sarcopenia) and circulating AAs between groups. Furthermore, there were no significant differences in PCSA assessed by MRI between active and inactive paediatric CD; however, age and gender were associated with muscle mass. These findings might have been affected by disease duration and further disease burden that need to be taken into consideration in future studies. Data collection in this thesis was significantly impacted by the COVID pandemic. Hence, most of the studies performed were either retrospective in nature or cross-sectional studies which require further prospective cohort studies with larger sample size to enhance generalisability and confirm findings. Therefore, the aims of this thesis were to a) systematically evaluate changes in skeletal muscle mass and function in paediatric IBD, b) investigate the relationship between adiposity and age of disease onset with adverse clinical outcomes in paediatric patients with CD, c) assess protein intake, circulating AAs and skeletal muscle mass and evaluate eating behaviour in paediatric CD and age, sex and BMI-matched healthy controls and d) describe the differences in PCSA assessed by MRI between active and inactive paediatric CD and examine the impact of age, gender, disease activity, and other disease-related variables on muscle mass. This research integrated several approaches to assess the impact of nutritional status, early age of disease onset on disease outcomes, and muscle size in paediatric CD patients. In addition, it compared protein intake, eating behaviour between children with stable CD and healthy matched peers to offer a holistic understanding of their impact on muscle mass and strength (as an index of sarcopenia) and circulating amino acids profiles in paediatric CD. While the studies presented in this thesis did not reveal significant differences in certain aspects of dietary protein intake, muscle size and strength, they did highlight several areas requiring further investigation. The complicated nature of disease burden and activity, alongside paediatric growth, necessitates further research to better understand the definition, management and prevention of sarcopenia in paediatric CD patients.22 0Item Restricted PROTEIN NUTRITION IN PAEDIATRIC CROHN’S DISEASE(University of Nottingham, 2025) Aljilani, Bayan; Moran, Gordon; Tsintzas, KostasAltered nutritional status is well documented in Crohn’s disease patients, which may lead to low muscle mass and deteriorated function (sarcopenia) and adverse disease outcomes. Although a variety of experimental methods have assessed muscle mass and function in paediatric CD patients, there is no conclusive consensus on the definition of sarcopenia in those patients. However, most of the studies in the literature have showed reduction in muscle mass (MM), lean mass (LM) and fat-free mass (FFM) in paediatric CD compared with healthy controls or reference data. Historically, underweight was frequently linked with paediatric CD. However, recent evidence suggests a shift towards adiposity rather than underweight being prevalent in paediatric CD. Our knowledge of the relationship between adiposity and adverse disease outcomes in children with CD is limited. In addition, clinical characteristics of CD patients may vary depending on age at diagnosis. Moreover, adult CD patients exhibit altered nutritional status and eating behaviour that impact negatively on habitual dietary protein intake, protein metabolism and muscle mass. However, these relationships have never been investigated in paediatric CD. This PhD thesis used the gold standard technique, magnetic resonance imaging (MRI), to assess leg muscle volume in children with stable CD disease and compared it with matched healthy subjects. These findings were linked with dietary protein intake, fasting plasma amino acids (AAs) and eating behaviour traits. In addition, the MRI technique was used to compare psoas muscle cross sectional area (PCSA) between paediatric with active CD versus those with inactive CD. However, conclusive findings were limited due to small sample size in both studies. This thesis highlighted the need for standardisation of body composition and sarcopenia terminology, as well as the valid use of assessment tools in adequately powered populations with appropriately matched comparators, to establish a clear definition of sarcopenia and assess its prevalence in paediatric IBD. In addition, it revealed that adiposity is linked to poor clinical outcomes in a long-term follow-up cohort of paediatric-onset CD, and that the age at disease onset is also associated with negative clinical outcomes. Moreover, this thesis revealed comparable dietary protein and energy intake, and eating behaviour traits between stable CD paediatric patients and matched healthy controls, which may explain the lack of differences in leg muscle volume and handgrip strength (indices of sarcopenia) and circulating AAs between groups. Furthermore, there were no significant differences in PCSA assessed by MRI between active and inactive paediatric CD; however, age and gender were associated with muscle mass. These findings might have been affected by disease duration and further disease burden that need to be taken into consideration in future studies. Data collection in this thesis was significantly impacted by the COVID pandemic. Hence, most of the studies performed were either retrospective in nature or cross-sectional studies which require further prospective cohort studies with larger sample size to enhance generalisability and confirm findings. Therefore, the aims of this thesis were to a) systematically evaluate changes in skeletal muscle mass and function in paediatric IBD, b) investigate the relationship between adiposity and age of disease onset with adverse clinical outcomes in paediatric patients with CD, c) assess protein intake, circulating AAs and skeletal muscle mass and evaluate eating behaviour in paediatric CD and age, sex and BMI-matched healthy controls and d) describe the differences in PCSA assessed by MRI between active and inactive paediatric CD and examine the impact of age, gender, disease activity, and other disease-related variables on muscle mass. This research integrated several approaches to assess the impact of nutritional status, early age of disease onset on disease outcomes, and muscle size in paediatric CD patients. In addition, it compared protein intake, eating behaviour between children with stable CD and healthy matched peers to offer a holistic understanding of their impact on muscle mass and strength (as an index of sarcopenia) and circulating amino acids profiles in paediatric CD. While the studies presented in this thesis did not reveal significant differences in certain aspects of dietary protein intake, muscle size and strength, they did highlight several areas requiring further investigation. The complicated nature of disease burden and activity, alongside paediatric growth, necessitates further research to better understand the definition, management and prevention of sarcopenia in paediatric CD patients.11 0Item Restricted The Effectiveness and Feasibility of Neuromuscular Electrical Stimulation after Fragility Fracture(University of Nottingham, 2024) Alqurashi, Helal; Robinson, Katie; Gladman, John; Gordon, Adam; Masud, Tahir; Piasecki, MathewFrailty, the vulnerable state seen in older people due to the cumulative effects of ageing and disease, is characterised by loss of muscle mass and muscle strength (sarcopenia). Older people living with frailty are prone to falls and fragility fractures, which necessitate hospital admission, resulting in further muscle loss and eventually leading to further disability. Rehabilitation exercise can reduce these consequences but is not always possible or adequate due to factors such as pain and fatigue. An alternative or additional technique is Neuromuscular Electrical Stimulation (NMES), which stimulates muscle contractions via an electrical stimulus applied to the skin overlying the muscles. The aim of this PhD thesis was to investigate the feasibility and efficacy of NMES on neuromuscular function in patients after fragility fracture. To explore the evidence regarding the effectiveness of NMES in hospitalised patients, I conducted a systematic review and meta analysis. This is reported in Chapter 2. Across the 42 identified papers, NMES was proven to be safe, albeit with a small incidence of minor discomfort. The meta-analysis revealed that NMES had a small effect on muscle strength (moderate certainty) (SMD = 0.33; P < 0.00001), a moderate effect on muscle size (moderate certainty) (SMD = 0.66; P < 0.005), a small effect on walking performance (moderate certainty) (SMD = 0.48; P < 0.0001) and a small effect on functional mobility (low certainty) (SMD = 0.31; P < 0.05). There was a small and non-significant effect on health-related quality of life. However, the effects of NMES on length of hospital stay, and molecular and cellular biomarkers were unclear. These findings showed that NMES may be a promising intervention for rehabilitation after fragility fracture. I then contributed to and took over the management of a feasibility study of NMES in patients admitted to hospital due to fragility fractures. The main results of this are reported in Chapter 3. The aim of the study was to evaluate the feasibility and effectiveness of NMES in patients with fragility fractures. The objectives included assessing the willingness and ability of patients to receive NMES, examining compliance and acceptability of NMES treatment, and identifying recruitment parameters and suitable outcome measures for a randomised clinical trial with clinical outcomes. The study was conducted in two phases: 1) in the hospital only, and 2) hospital, rehabilitation centres, and participants’ homes. Patients with fragility fracture were randomised to receive NMES for 6 weeks/discharge either to the right or left leg, with the other leg serving as control. NMES was applied to quadriceps and tibialis anterior muscles for 30 minutes, 3 days/week. Sessions were progressed to achieve 60 minutes, 5-7 day/week. Feasibility outcomes included participant characteristics, recruitment rate, tolerability, and number of NMES sessions. Clinical outcomes included muscle strength, and ADL at six months. The findings showed that 1052 patients were identified, of whom 113 (11%) were eligible, and 29 (3%) were recruited (median Clinical Frailty Score 3, median Barthel ADL score 93/100). The recruitment rate was 0.45/week in phase 1 and 0.9/week in phase 2. 53% achieved the target of 24 NMES sessions. 5/29 withdrew due to intolerance of NMES. Leg muscle strength improved in both treated and untreated legs, with marginally greater improvement observed in the tibialis anterior of treated legs. It became clear during the feasibility study that hospital-based NMES was unlikely to be feasible, but that NMES might be more feasible if home-based NMES. In view of the limited use of this technique in fragility fracture patients at home, I utilised an action research iv approach to optimise the use of NMES in this group and setting whilst the feasibility study continued. The findings of this and those of semi structured interviews of participants reported in Chapter 4. The observational process highlighted issues related to the stimulation of tibialis anterior muscle, which could be overcome. Themes identified through interview included acceptability, safety, practicality, user experience, training, and support, and how and when. This sub-study reinforced the findings of the quantitative aspect of the feasibility study, confirming the safety and acceptability of NMES. In summary, my literature review has indicated that NMES is a potentially useful treatment to prevent and reverse the muscular consequences of hospitalisation for fragility fracture. Furthermore, the feasibility study has shown that trials of NMES in fragility fractures are feasible, albeit in a minority of mildly frail fragility fracture patients with little premorbid disability. I have argued that such trials should use home-based, self-administered NMES, and should consider this intervention as an adjunct to, rather than a replacement of, a rehabilitation programme. Additionally, the findings derived from this thesis serve as valuable insights for designing future randomised controlled trials, which is a necessary step before NMES becomes a routine part of clinical care.17 0Item Restricted Rapid review of longitudinal studies on the association between oral health and frailty(King’s College London , 2024-08) Alhumaidi, Meshari; sabbah, waelAbstract Background Frailty and sarcopenia are prevalent conditions in the elderly, contributing to increased healthcare costs and higher mortality rates. Poor oral health, characterized by issues such as tooth loss and periodontal disease, has been associated with the onset and progression of these conditions. Despite this, there is a lack of comprehensive longitudinal studies examining the relationship between oral health and frailty in older populations. Objective This rapid review aims to consolidate and analyse the existing body of research from longitudinal studies on the association between various oral health conditions and frailty among older adults. The goal is to identify key oral health issues that significantly impact frailty and to provide insights for healthcare providers and policymakers. Methods The review systematically gathered and synthesized data from relevant studies using a standardized methodological approach. It focused on studies involving older adults aged 65 and above, examining conditions such as tooth loss, periodontal diseases, and overall oral hygiene status. The analysis included comparisons between individuals with poor oral health and those with healthier oral conditions, assessing the impact on frailty indicators. From an initial search yielding 1404 records (702 from PubMed, 93 from Ovid, and 609 from Cochrane Library), 609 records remained after removing duplicates. After screening titles and abstracts, 16 articles were assessed for eligibility. Ultimately, 11 studies met the inclusion criteria and were included in the final review. Results The findings highlight significant associations between poor oral health and increased frailty in the elderly. Conditions like tooth loss and periodontal disease were found to be major risk factors for frailty, affecting physical functions such as strength, mobility, and overall vitality. The review also identified gaps in the literature, particularly the need for more longitudinal studies to establish causal relationships. A total of 11 longitudinal studies met the inclusion criteria and were included in this systematic review. These studies provide valuable insights into the association between various oral health conditions and frailty among older adults, highlighting the importance of maintaining good oral health to mitigate the progression of frailty. However, the predominance of cross-sectional designs in some studies limits the ability to establish causal relationships and introduces potential biases, including measurement bias from self-reported data and residual confounding. Conclusion The review underscores the importance of integrating oral health assessments into routine geriatric care. Early interventions targeting oral health could potentially delay the onset of frailty, improving quality of life and reducing healthcare costs. These findings provide a foundation for developing comprehensive geriatric care models that prioritize oral health and for future research to address the identified gaps in the literature.23 0Item Restricted The Feasibility of Pulmonary Rehabilitation in Patients with Interstitial Lung Diseases Including Patients with Combined Pulmonary Fibrosis and Emphysema(2023-08-14) Alsomali, Hana; Ward, ChrisIntroduction: Interstitial lung diseases (ILD) are characterized by interstitial inflammation or fibrosis, leading to impaired gas exchange, shortness of breath, decreased exercise tolerance, and reduced quality of life. Combined pulmonary fibrosis and emphysema (CPFE) is the co-existing presence of pulmonary fibrosis and emphysema. Data describing the experience of tailored pulmonary rehabilitation program (PRP) in people with ILD is rare and in particular in patients with CPFE are lacking. This PhD aimed to determine the characteristics and prognosis of patients with CPFE in a United Kingdom cohort, and to assess the feasibility of inspiratory muscle training (IMT) as part of a PRP for patients with ILD including patients with CPFE. Methods: A five-year retrospective single centre study was conducted at the regional ILD clinic. Then a feasibility study with a randomized controlled trial design was conducted Patients were randomized into intervention group IMT + PRP and a control group PRP only. The IMT was performed using POWERBreathe® twice daily. The PRP consisted of one session a week for 6-8 weeks. Results: Retrospective study showed that 203 patients with CPFE were diagnosed. Mean age and Body Mass Index (BMI) for patients with CPFE were 72 years (SD = 8.7), and 28.1 kg/m² (SD = 4.4) respectively. Median survival time for patients with idiopathic pulmonary fibrosis (IPF) subtype CPFE n= 93 was 3.2 years (2.1-4.2).. Kaplan Meier analysis showed statistically significant differences between Gender at birth-Age-Physiology (GAP) stages with a p-value of 0.012 in patients with IPF subtype CPFE. PRP had an attendance and completion rates of mean of 87% and 64% respectively. No side effects were reported during the study. The maximum inspiratory pressure (MIP) improved in all participants. Conclusion: Patients with CPFE were relatively old, majority male, with a history of smoking, and had poor prognosis. The GAP index and staging system demonstrated prognostic capability in patients with IPF subtype CPFE. At least half the patients with CPFE were not referred to PRP, indicating low referral rates. A tailored PRP program was feasible and well received in patients with CPFE, indicating that this was a viable and beneficial treatment option for patients with CPFE where therapeutic options are limited.5 0