Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients—a CERTAIN registry analysis

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. Methods: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. Results: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. Conclusion: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated. Keywords: gout; long-term outcome; pediatric kidney transplantation; uric acid; uric acid-lowering therapy

The Use of Routinely Collected Data in Clinical Trial Research

RCTs are the gold standard for assessing the effects of medical interventions, but they also pose many challenges, including the often-high costs in conducting them and a potential lack of generalizability of their findings. The recent increase in the availability of so called routinely collected data (RCD) sources has led to great interest in their application to support RCTs in an effort to increase the efficiency of conducting clinical trials. We define all RCTs augmented by RCD in any form as RCD-RCTs. A major subset of RCD-RCTs are performed at the point of care using electronic health records (EHRs) and are referred to as point-of-care research (POC-R). RCD-RCTs offer several advantages over traditional trials regarding patient recruitment and data collection, and beyond. Using highly standardized EHR and registry data allows to assess patient characteristics for trial eligibility and to examine treatment effects through routinely collected endpoints or by linkage to other data sources like mortality registries. Thus, RCD can be used to augment traditional RCTs by providing a sampling framework for patient recruitment and by directly measuring patient relevant outcomes. The result of these efforts is the generation of real-world evidence (RWE). Nevertheless, the utilization of RCD in clinical research brings novel methodological challenges, and issues related to data quality are frequently discussed, which need to be considered for RCD-RCTs. Some of the limitations surrounding RCD use in RCTs relate to data quality, data availability, ethical and informed consent challenges, and lack of endpoint adjudication which may all lead to uncertainties in the validity of their results. The purpose of this thesis is to help fill the aforementioned research gaps in RCD-RCTs, encompassing tasks such as assessing their current application in clinical research and evaluating the methodological and technical challenges in performing them. Furthermore, it aims to assess the reporting quality of published reports on RCD-RCTs

Can routinely collected electronic health data be used to develop novel healthcare associated infection surveillance tools?

Background: Healthcare associated infections (HCAI) pose a significant burden to health systems both within the UK and internationally. Surveillance is an essential component to any infection control programme, however traditional surveillance systems are time consuming and costly. Large amounts of electronic routine data are collected within the English NHS, yet these are not currently exploited for HCAI surveillance. Aim: To investigate whether routinely collected electronic hospital data can be exploited for HCAI surveillance within the NHS. Methods: This thesis made use of local linked electronic health data from Imperial College Healthcare NHS Trust, including information on patient admissions, discharges, diagnoses, procedures, laboratory tests, diagnostic imaging requests and traditional infection surveillance data. To establish the evidence base on surveillance and risks of HCAI, two literature reviews were carried out. Based on these, three types of innovative surveillance tools were generated and assessed for their utility and applicability. Results: The key findings were firstly the emerging importance of automated and syndromic surveillance in infection surveillance, but the lack of investigation and application of these tools within the NHS. Syndromic surveillance of surgical site infections was successful in coronary artery bypass graft patients; however it was an inappropriate methodology for caesarean section patients. Automated case detection of healthcare associated urinary tract infections, based on electronic microbiology data, demonstrated similar rates of infection to those recorded during a point prevalence survey. Routine administrative data demonstrated mixed utility in the creation of simplified risk scores or infection, with poorly performing risk models of surgical site infections but reasonable model fit for HCA UTI. Conclusion: Whilst in principle routine administrative data can be used to generate novel surveillance tools for healthcare associated infections; in reality it is not yet practical within the IT infrastructure of the NHS

Feasibility and utility of a sickle cell disease registry for research and patient management

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis aimed to evaluate the feasibility and utility of a sickle cell disease registry for clinical patient management and research. Five hospitals out of nine in the North West London health region participated in the registry, with 78 percent coverage of the sickle cell disease population. There was 80% case ascertainment in participating hospitals. Aggregated anonymised demographic and diagnostic data was collected for all haemoglobinopathy patients. This provided the core dataset for quantifying prevalence of sickle cell and thalassaemia and mapping local hospital workloads and service requirements. Thirteen percent of HbSS adult patients were taking hydroxycarbamide. The cohort of patients treated with hydroxycarbamide was evaluated. Sixty two of the 80 patients started on treatment were included. Follow-up was censored after 9 years, totalling 249 person-years of data with a median follow-up of three years (IQR, 1-6). Results showed that haematological benefits were maintained in the long-term with treatment, but evidence of long-term clinical effectiveness was less strong. This appeared to be due to the patterns of clinical management in everyday practice. Patients tend to be treated with modest doses of hydroxycarbamide due to intolerance or inability to attain or maintain maximum tolerated dose. For example maximum tolerated dose was the aim of treatment for 91% of patients but it was achieved for 65% of participants. Non- compliance with treatment and monitoring schedule was the main reason for non- attainment. Results suggest that it is sensible to strive for maximum tolerated dose to ensure therapy remains effective, but with more realistic expectations of the dose patients can attain and maintain. Doses in adult patients average 20mg/kg/day and 25mg/kg/day in children. Adult patients may be able to achieve a higher dose, if there was more stringent monitoring and improved management of non-compliance. The North West London HU Sub-Registry proved useful for measuring long-term effectiveness and tolerability of hydroxycarbamide. Routinely collected data was utilized for both clinical management and research purposes. The novelty lay in examination of the nuances of routine clinical practice. An electronic patient record was developed as a clinical management tool. It is the first study reporting long-term outcomes for UK sickle cell disease patients on hydroxycarbamide. Findings should help clinicians devise effective treatment protocols and strategies for managing patients commenced on this therapy. Interventions need to be targeted at increasing utilisation, patient adherence and persistence with treatment. The electronic patient record could be used to maximise treatment benefit and improve adherence. More effective involvement of the multidisciplinary team and primary care colleagues in patient education and management should improve usage. Patients and carers need up to date and easy to assimilate information to make informed decisions about treatment options. Maintaining a SCD registry is challenging. Models which operate as clinical information systems provide an incentive for participation. These enable active involvement of local care providers in registry management and the ability to keep and utilize their own data. Clinicians require accurate and current data for patient management and to enable them to benchmark their local outcomes against national outcomes and care standards

Cancer in the Arab World

This is an Open Access book. This book is a must-have for healthcare providers and researchers, public health specialists and policy makers who are interested and involved in cancer care in the Arab world. The Arab world consists of 22 countries, which are members of the Arab League and spanning over 13,132,327 km2 with over 423,000,000 population. Over the past few decades, the Arab world has witnessed a swift evolution in healthcare provision. Nonetheless, Arab countries have considerable variability in economic capabilities, resource allocation, and intellectual talent that inevitably reflect on access to modern cancer care and prevention. This book is authored by experts from the Arab world who provide vital information on cancer statistics and risk factors, available clinical care pathways and infrastructure, and prevention programs in their individual countries. The chapters also address specific challenges in each country and insights into future directions to achieve optimal care with conventional and novel diagnostics and therapies to keep up with the era of precision medicine. Special topics of interest and unique to the Arab world are also discussed, such as out of the country’s medical tourism for cancer care and cancer care during war and conflict. Other special chapters include: Cancer research in the Arab world, Radiation therapy in Arab World and Pediatric Oncology in the Arab World Cancer in the Arab World is the first comprehensive book that addresses cancer care in depth in all Arab countries and it is endorsed by the prestigious Emirates Oncology Society

Cancer in the Arab World

This is an Open Access book. This book is a must-have for healthcare providers and researchers, public health specialists and policy makers who are interested and involved in cancer care in the Arab world. The Arab world consists of 22 countries, which are members of the Arab League and spanning over 13,132,327 km2 with over 423,000,000 population. Over the past few decades, the Arab world has witnessed a swift evolution in healthcare provision. Nonetheless, Arab countries have considerable variability in economic capabilities, resource allocation, and intellectual talent that inevitably reflect on access to modern cancer care and prevention. This book is authored by experts from the Arab world who provide vital information on cancer statistics and risk factors, available clinical care pathways and infrastructure, and prevention programs in their individual countries. The chapters also address specific challenges in each country and insights into future directions to achieve optimal care with conventional and novel diagnostics and therapies to keep up with the era of precision medicine. Special topics of interest and unique to the Arab world are also discussed, such as out of the country’s medical tourism for cancer care and cancer care during war and conflict. Other special chapters include: Cancer research in the Arab world, Radiation therapy in Arab World and Pediatric Oncology in the Arab World Cancer in the Arab World is the first comprehensive book that addresses cancer care in depth in all Arab countries and it is endorsed by the prestigious Emirates Oncology Society

Treatment outcomes and medication management of tuberculosis

Tuberculosis (TB) is a bacterial infectious disease. The majority of TB patients in the Netherlands are successfully treated but in some patientsextension of treatment duration is necessary due to complications. Only in a small number of patients this treatment fails. This thesis focuses on the multifaceted medical approach to optimize the treatment of TB and improve treatment outcomes.In the first part of this thesis, we used long-term data from the national tuberculosis registry to determine the risk factors of prolonged and unsuccessful TB treatment in different patients. By identifying risk factors at an early stage, appropriate measures can be taken to reduce their impact and improve TB treatment outcomes. In the second part of this thesis, we evaluated the efficacy of a well-known antibiotic called levofloxacin. We investigated the relationship between the amount of antibiotic in the blood and the effectiveness of the treatment, and side effects by combining and analyzing data from previous studies. We also investigated in patients with a highly resistant form of TB whether they had enough of the antibiotic in their blood to kill the bacteria.Based on this research, we conclude that the amount of antibiotic in the blood differs per patient, and monitoring of this value combined with measuring the sensitivity of the bacteria to the antibiotic is necessary to adjust the dosage and thereby optimize treatment