Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa

Includes bibliographical references.Aims : 1. To determine the proportion of patients who present with TB treatment and or ART-associated drug-induced liver injury (DILI) amongst all patients presenting with significant liver injury to GF Jooste Hospital during the study period. 2. To describe base line clinical characteristics and management of TB treatment and or ART-associated DILI patients. 3. To describe the in-patient and 3-month mortality of TB treatment and or ART-associated DILI patients. Background and Rationale : GF Jooste Hospital is a public sector referral hospital and serves a densely populated area with a high burden of HIV and tuberculosis (TB). ART rollout in the Western Cape started in 2001/2002 at two pilot clinics and is now well established (1). Many patients are on concomitant TB treatment and ART. At ART clinics in the referral area 25 - 40% of patients are on TB treatment when they start ART (2, 3) . At GF Jooste hospital many HIV positive patients are seen who are on TB treatment and or ART, and present with symptomatic liver dysfunction. Patients are on multiple hepatotoxic drugs, may have multiple opportunistic infections, systemic sepsis and hepatic TB immune reconstitution disease also plays a role. Anecdotally, these patients are complex to manage, require frequent specialist input, spend a long time in hospital and have high mortality. Management guidelines are based on expert opinion and is not evidence based. In practice management relies heavily on the attending clinicians’ experience and clinical judgment and management often differ widely between clinicians. Mortality could be due to progression of TB and or HIV because of interruption of effective therapy, other opportunistic infections or hospital acquired infections. Few early liver biopsies are done and it is not known if early liver biopsies would aid by guiding management of these patients. Prospective studies are urgently needed to guide management in these patients. The burden of TB treatment and or ART-associated drug induced liver injury in this setting has not been described to our knowledge, neither has management, outcome or mortality. This study was performed to aid planning of prospective studies in this field

Diagnosis, treatment and long-term consequences of hyperthyroidism: use of existing data to generate new knowledge

Hyperthyroidism is a common endocrine disorder with multiple aetiologies, manifestations and potential therapies. This thesis explores the challenges relating to the diagnosis, treatment and long-term consequences of thyrotoxicosis in real-world outpatient and inpatient settings. We performed a number of epidemiological studies analysing data from large, detailed, routinely collected data sources. We confirmed that classical manifestations of hyperthyroidism are significantly less prevalent in older patients and established that newly diagnosed thyroid dysfunction is rare in hospitalised subjects despite high volume thyroid function testing in this setting where we found a high proportion of abnormal thyroid tests in those with pre-existing thyroid dysfunction. We determined that thionamides are effective in a half of subjects treated with a prolonged course and that appropriate patient selection improves success rates. We established that treatment of hyperthyroidism with radioactive iodine results in more weight gain than antithyroid drugs and that hyperthyroidism in hospitalised patients is associated with longer hospital stays, higher frequency of admissions and increased mortality. In conclusion, this thesis provides important new insights into the diagnosis and treatment of hyperthyroidism and highlights that correct evaluation and management of patients may minimise the long-term consequences associated with this common disorder

Energy Expenditure in Kidney Failure: Implications for Management

Renal replacement therapy, in the form of dialysis or transplantation, is the cornerstone of management for end-stage renal disease. UK renal registry shows nearly half of those needing renal replacement therapy are treated by dialysis – predominantly by haemodialysis. Patients on renal replacement therapy have increased mortality risk compared to age matched general population. Moreover, some specific subgroups of patients on haemodialysis have increased risk of mortality than expected. The survival benefit seen in women in the general population is attenuated resulting in similar survival for men and women on haemodialysis therapy. In addition, obese individuals and those of non-Caucasian origin have better survival outcome. Though the underlying reason for these findings is not clear and is likely to be multi-factorial, it has been hypothesised that this paradox could be due to the current practice of normalising dialysis dose to total body water. A number of metabolic factors – body surface area, resting energy expenditure and total energy expenditure – have been proposed as alternative to total body water for scaling dialysis dose. There were two overarching aims of this work – one was to study the effect of declining renal function on resting and total energy expenditure and to study the influence of various energy expenditure measures on uraemic toxin generation. The second was to study the impact on survival outcome of using these alternate parameters for normalising dialysis dose and to derive dialysis dose adjustments based on these metabolic parameters. In order to study these aims, studies were designed to explore different aspects of energy expenditure measures along with a longitudinal study to examine the impact of these parameters on survival outcome. The relationship between energy metabolism, body composition and uraemic toxin generation was studied with a retrospective analysis of 166 haemodialysis patients in whom urea generation rate was used as surrogate marker of uraemic toxin generation. It was found that total energy expenditure and fat-free mass predicted uraemic toxin generation after adjustment for other relevant variables. This study provided the preliminary data which was useful in designing further studies for this work. The effect of renal function on resting and total energy expenditure was studied in 80 patients with varying stages of chronic kidney disease who were not on renal replacement therapy. Resting and total energy expenditures were measured directly using gold-standard methods. It was found that declining renal function did not have a significant influence on either of these measures. This supports the hypothesis that metabolic rate is the driving force for glomerular filtration rate and not vice-versa. The directly measured energy expenditure measures were also found to have a moderately strong relationship with urea generation rate in these patients not on renal replacement therapy. The impact of physical activity on uraemic toxin generation, and thereby dialysis requirement, was studied in a prospective cross-sectional study of 120 haemodialysis patients in whom the physical activity was measured by an accelerometer device. Results from the study showed physical activity level to be a significant predictor of uraemic toxin generation after adjustment for gender and body size differences. This study results stressed the importance of adjusting dialysis dose based on individual’s physical activity level. To study the impact of using metabolic factors as normalising parameter for scaling dialysis dose on survival outcome, a large-scale longitudinal study was conducted with 1500 maintenance haemodialysis patients recruited for the study. Dialysis dose-related parameters and survival outcomes were collected at baseline and at various time points during the follow-up period of 18 months. Study results were analysed in two parts - the theoretical basis for using these metabolic factors as scaling parameters was explored which showed that current minimum target dialysis dose risks under-dialysis in certain subgroups of patients and using these alternative parameters may provide a more equivalent dialysis dose across individuals of different body sizes and gender. With these results arguing for potential use of the alternative parameters, the impact on survival of using them were examined. It was found that all three parameters performed better than the current parameter (total body water) with regards to predicting mortality. Total energy expenditure was found to be the best parameter with the lowest hazard ratio for risk of death. The study data was also analysed to derive an algorithm for adjustment of minimum target dialysis dose based on body size and physical activity level. This newly derived minimum dose target was also shown to impact on survival with those underdialysed based on this criteria having poorer survival outcomes. To understand the impact of whole body protein turnover on resting energy expenditure and uraemic toxin generation, a cross-sectional study was conducted on 12 patients with advanced CKD – 6 each in pre-dialysis CKD and haemodialysis group. It was found that haemodialysis patients had higher rate of protein turnover compared to pre-dialysis patients. Whole body protein turnover was found to contribute significantly to resting energy expenditure and had a moderately strong relationship with urea generation rate. In the course of these studies, two questionnaire tools have been validated for use for clinical and research purposes – one is a self-report comorbidity questionnaire and the other, the Recent Physical Activity Questionnaire. The comorbidity questionnaire was developed as part of this work and was validated against Charlson Comorbidity Index. The Recent Physical Activity Questionnaire was validated for physical activity data collection and energy expenditure calculation against the gold-standard doubly labelled water method. In conclusion, it has been demonstrated that metabolic factors such as body surface area, resting energy expenditure and total energy expenditure are more closely related to uraemic toxin generation compared to total body water. It has also been demonstrated that physical activity contributes to metabolic waste production and may necessitate changes in dialysis requirement. It has been shown that these metabolic factors, when used as scaling parameter for dialysis dosing, may predict survival better than the current parameter in use. The algorithm for dialysis dose adjustment and the questionnaires validated in this work have provided novel tools for further research studies and clinical practice. The central hypothesis of this work is that some metabolic factors may be better markers of uraemic toxin generation compared to total body water. It is hypothesised that modifications in dialysis practice based on these factors may improve the quality of haemodialysis and favourably impact on survival outcome for patients with end-stage renal disease. The work presented here largely supports this hypothesis

A profile of surgical complications in gynaecology at a teaching hospital in South Africa

Obstetrics and Gynaecolog

Health Disparities 2018: Closing the Gap

With the theme of “Health Disparities: Closing the Gap,” this symposium aims to showcase the work done by researchers here in the Valley and beyond toward improving the health and well-being of the communities they serve and society as a whole

2018 February

Press releases for February of 2018

Atrial Fibrillation and Stroke:State-of-the-art and future directions

Stroke is a major complication of atrial fibrillation (AF). About 25% of ischaemic stroke are cardio-embolic in origin; AF is the most common cause of those.1 Nonvalvular AF carries a 5-fold increased risk of stroke,2 while AF related to mitral stenosis increases the risk of stroke by 20-fold.3 The attributable risk of stroke for AF increases with age unlike other factors such as hypertension for instance.4When the AF is asymptomatic but detected on a cardiac implantable electronic device (CIED) or a wearable monitor, it is described as being subclinical. It is suspected that subclinical AF might be the cause of cryptogenic strokes (i.e., strokes of unknown aetiology).5 While previous studies showed that atrial high-rate events (AHREs) detected on a CIED were associated with increased risk of stroke,5,6 treating such episodes with anticoagulation has not been shown to reduce the risk of stroke. In fact, anticoagulation in these cases resulted in higher incidence of a composite of death or major bleeding, mainly driven by the increased risk of bleeding.7Not only that AF can cause stroke and vice versa,8 but stroke patients with AF were shown have higher stroke severity and mortality compared to those without.9 The effect of AF on mortality rate was primarily driven by stroke severity.9 The worse clinical and imaging outcome in AF-related strokes was attributed to bigger volumes of more severely hypo-perfused tissues, resulting in larger infarct size and higher risk of haemorrhagic transformation.10In this narrative review article, we provided an overview of the burden of AF and stroke, the complex interplay between the two conditions, as well as the treatment and secondary prevention of stroke in patients with AF. We comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic

Risk stratification for women undergoing in-vitro fertilisation treatment

The aim of this thesis was to explore three factors that are easily available and contribute important information for women before commencing in-vitro fertilisation (IVF) treatment: ethnicity, body-mass index (BMI) and thyroid disease. Results of the systematic review, cohort study and meta-analysis investigating ethnicity and IVF outcome showed South Asian and Black women have lower adjusted live-birth (LB) rates, after fresh cycle treatment, compared with White women. The relationship between BMI and IVF outcome was explored in a prediction model estimating chances of LB following first cycle. The model found BMI has reduced effect on IVF outcome when adjusting for other confounders such as age. The prevalence of thyroid dysfunction and thyroid peroxidase antibodies (TPOAb) was examined across the UK in >7000 women of reproductive age, and a cohort study investigating the effect of subclinical hypothyroidism (SCH) on IVF outcome was also performed. The prevalence of overt thyroid disease was 0.38% and subclinical disease 3.45%. Using an upper limit cut off for thyroid-stimulating hormone of 2.5mU/L the prevalence of SCH was 19.64%. The overall prevalence of TPOAb was 9.11%; this was 7.98% in euthyroid women. Finally, there were no significant differences in LB between euthyroid women and women with SCH