Background Stroke guidelines recommend treatment of acute stroke as a medical emergency. In many countries prolonged delays occur before patients with acute stroke receive medical attention. Only a small percentage of patients are assessed in hospital within the time window for reperfusion therapy. There is limited available published data concerning barriers to acute stroke care in South African patients. The aim of this study was to determine the pre-hospital barriers and in-hospital delays to emergency care for patients presenting to Groote Schuur Hospital (GSH) with acute stroke. Methods Eligible patients included were those with a clinical and radiological diagnosis of acute stroke who presented to GSH Emergency Unit and required admission for more than 24 hours. The study was a prospective, observational study with two components: a semi structured interviewer administered questionnaire and a record review of ischaemic stroke patients’ clinical notes within 48 hours of admission to GSH. GSH is a tertiary/academic level hospital in Cape Town, Western Cape province, South Africa. Recruitment took place over a 6-week period. Results Demographics: 50 patients were included, with a median age of 61,5 (IQR 44,7 – 70,2) years; gender: females, 29 (58%). Ethnicity: Mixed African ancestry 38 (76%), Black 11 (22%). Pre- hospital barriers: The median distance to hospital was 12,7 (IQR 10,2 – 17,6) km. Most patients 32 (64%) called for assistance immediately. Frequent reasons cited for delays: waiting for improvement, 7 (38,9%) and failure of symptom recognition 4 (22%). Most patients used their own private transport, 32 (64%) and half of the patients (25) presented directly to GSH. In- hospital delays: The median time interval from arrival at the Emergency Unit to doctor assessment for all the patients was 67,5 (IQR 19,75 – 128,5) minutes. The median door to CT brain time interval for all patients was 5,1 (IQR 1,7 – 10,2) hours and 3,1 (IQR 0,8 – 9,6) hours for those patients that arrived within the thrombolysis time window. Only 21 of 50 patients were referred and assessed by the stroke unit team. Only 3 of the 21 patients received intravenous thrombolysis and none received mechanical thrombectomy. Conclusion: There majority of the patients who arrived at GSH early after symptom onset used their own private transport and lived close to hospital. Pre-hospital barriers were failure to recognize symptoms, patients hoping for clinical improvement, delays in ambulance transport and routing via secondary hospitals. In hospital delays were prolonged door to doctor assessment and door to CT Brain time intervals.

INTRODUCTION Guillain-Barré syndrome (GBS) or acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is an important cause of acute severe and life-threatening weakness. It occurs worldwide and may affect all age groups, but varies widely in clinical presentation, subtype, electrophysiology, course and outcome. There is sparse literature on GBS in low and middle income countries (LMIC), and the effect, if any, of HIV on GBS. This observational cohort study aims to describe the clinical presentation and outcome of acute GBS in Cape Town, South Africa, in participants recruited into the International Guillain-Barré Syndrome Outcome Study (IGOS). A secondary aim, given the high HIV prevalence in South Africa, is to describe and compare GBS participants with and without HIV infection. METHODS Between 1 June 2014 and 31 January 2017, we recruited participants 18 years or older presenting to Groote Schuur Hospital in Cape Town with acute GBS (< 2 weeks onset of symptoms) who were available for 1 year follow up. We recorded demographic, clinical, laboratory, electrophysiological and treatment data at entry. At follow-up at weeks 4, 26 and 52, GBS-related complications and GBS disability scale scores (GDSs) were evaluated. A good outcome was defined as the ability to walk unaided (GDSs 2) by 6 months. The clinical presentation and outcomes of HIV-uninfected and -infected participants were compared. RESULTS: Of 31 recruited participants, 1 participant was re-diagnosed as acute onset-CIDP and excluded from the study and 1 participant demised of an unrelated cause within the first week. 19 participants were male and the median age was 40 years. Reported antecedent infections (73%), co-morbid HIV infection (30%) and tuberculosis (15%) were frequently seen. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP; 67%) and acute motor axonal neuropathy (AMAN; 17%) were the most common phenotypes. Overall, GBS-related complications occurred in 46% of participants. The major complication was pneumonia which occurred in 23% of the total group, and all required intubation/ventilation. Other septic complications (drip site or systemic) were less common, 6% of the entire group. At entry, 83% had GDSs >4 indicating severe disability. The ability to walk unaided was regained by 37% at 4 weeks, 75% at 6 months and 79% at 1 year. Three participants remained severely affected at 1 year (GDSs of >3). There were no differences in antecedent infections, treatments given, or motor outcomes between HIV-infected and -uninfected GBS participants apart from a trend towards higher CSF protein in the HIV-infected group (p-value 0.05). AIDP was the most common GBS variant in both groups. AMAN was only seen in the HIV-uninfected group, whereas Miller Fisher 5 syndrome (MFS) was more common in the HIV-infected group. However, the numbers were too small to reach statistical significance. CONCLUSION Infections with HIV and tuberculosis frequently co-occurred with acute GBS, whether this reflects true disease association or merely high background disease prevalence cannot be confirmed by this study. AIDP is the most common phenotype unlike other LMIC regions such as Asia where AMAN predominates. In this cohort, 76% of participants showed good outcomes being able to walk unaided or having no/minor symptoms by 6 months. However, of the remainder only 1 showed significant recovery at 1 year. HIV participants had similar clinical presentations, complications and outcomes compared to the HIV-uninfected group. Mortality was low.

Background Peri-operative physicians increasingly acknowledge that fluid management influences patient outcome. Studies have attempted to understand the changes in practice following recently published evidence, although none have included significant contributions from South Africa. Methods An observational cohort study using an interactive online survey was conducted. Five underlying questions where highlighted during data analysis and these data were summarized into simplified categories for better comparison. Results Three hundred questionnaires where completed. During resuscitation of an unstable trauma patient, 233/300 (78%) use crystalloids, although 107/300 (36%) prefer blood products if available. Synthetic colloids for trauma patients unresponsive to initial fluid (normal haemoglobin) would be chosen first by 179/300 (60%), and 12/28 (46%) of non-anaesthesia physicians prefer blood products. Of interest, 10/300 (3%) would use either albumin or hypertonic saline when resuscitating a non-responding trauma patient. Concerning was 14/300 (5%) of respondents who would use fluid other than blood products for trauma patients with low haemoglobin. A relatively large proportion 47/300 (16%) would use synthetic colloids to resuscitate haemodynamically unstable septic patients. Conclusion The results presented are largely from anaesthesia practitioners and practice follows international trends. However, synthetic colloids are used in septic patients where evidence suggests otherwise. A lack of access to blood products probably influences practice. Findings suggest the need for continued attempts to translate research into clinical practice.

Within the context of health system strengthening and pharmaceutical systems development goals, a population must have equitable access to quality affordable medicines and pharmaceutical supplies. The utilization of the private (for-profit and not-for-profit) pharmaceutical sector actors by the public to promote universal access to quality medicines and related commodities is an increasingly common practice in resource poor settings. Faith-based drug supply organizations (FB-DSOs), as a component of the private-not-for-profit (PNFP) sector, are increasingly involved in the supply of pharmaceuticals to complement public sector efforts in wider coverage of communities in Africa. However, their role in the pharmaceutical system in Africa is not well defined. This paper presents the results of a systematic review conducted to map out the organization of pharmaceutical systems and establish the role of faith-based health care providers in the pharmaceutical supply chain in Africa. For this study, a scoping review was first conducted to map the literature on pharmaceutical supply chains in low- and middle-income countries (LMICs), understand the challenges facing pharmaceutical supply chainsin LMICs and the role faith-based health care providers play in the pharmaceutical supply chain. After this, a qualitative systematic review was conducted across multiple electronic databases to identify documents that contain information on faith-based involvement in pharmaceutical supply chain in Africa. Citation tracking was used to identify further relevant articles. Included materials were analyzed using thematic narrative analysis and synthesized. The public pharmaceutical supply chain in Africa is faced with challenges including drug stock outs and irregular supplies, shortage of trained pharmacy personnel and lack of system for drug regulation and quality assurance. Faith-based health care providers involved in pharmaceutical supply chain do exist extensively as drug supply organizations or as a Christian Health Association with a pharmaceutical supply chain. They have been in existence in Africa for a very long time now contributing to the national pharmaceutical system in Africa. The review revealed that faith-based involvement in pharmaceutical chains tended to improve access to the general population and inserted additional pharmaceutical supplies into the national pharmaceutical system - which tended to strengthen the broader public private partnership between faith-based health providers and the public sector. This analysis confirmed that African pharmaceutical supply systems continue to face challenges. There is a major evidence gap relating to PNFP contribution to pharmaceutical systems - as is evidenced by this study on faith-based contributions to African pharmaceutical systems (which can be understood as a tracer for a broader concern). There is a particular lack of evidence about the national supply chain, and how faith-based PNFP engagement contribute or detract from the national pharmaceuticalsupply chain. FB-DSOs complement the public pharmaceutical system by improving access to medicines and related commodities in Africa.

Includes bibliographical references (leaves 108-112). / Strain is a measure of cardiac deformation and provides information on the mechanical and functional properties of the heart. As this deformation occurs in three dimensions (3D), a 3D measure of strain is appropriate, however, currently the procedures for measuring 3D intramyocardial strain fields are limited to a handful of techniques. The only widely accepted method being the use of tagging in orthogonal image planes that requires the imaging of the entire myocardial volume, followed by lengthy and time consuming post processing. A method to combine cine displacement encoding with stimulated echoes (cine-DENSE) and cine strain encoded MRI (cine-SENC) for the formulation of the complete 3D strain tensor field for a single slice of myocardium is proposed.

Bibliography: leaves 133-139. / Research has suggested an association between the angiotensen-I converting enzyme (aCE) insertion/deletion (I/D) polymorphism and endurance performance, skeletal and cardiac muscle hypertrophy and performance in power associated sporting events. The nitric oxide synthase (ecNOS) G894T polymorphism is associated with endurance training induced decreased submaximal diastolic blood pressure and nitric oxide is a direct modulator of ACE activity.

Includes abstract. / Includes bibliographilcal references. / Myocardial infarction (MI) is a principal cause of cardiovascular morbidity and mortality that is associated with other systemic complications. In the heart, MI can result in pump dysfunction, inducing cardiac hypertrophy which may become maladaptive leading to heart failure (HF). In the brain, MI is associated with psychological disorders such as anxiety and depression. Many pharmacological agents have been identified to modulate MI and hypertrophy development.

Includes abstract. / Includes bibliographical references. / Photodynamic Rejuvenation (PDR) is a novel therapy used to treat the signs of skin ageing. It is a promising dermatological therapy due to its less severe side effects and superior results when compared to other chemical treatments. This therapy involves the topical application of a photosensitizing drug (PS) which is activated by a specific wavelength of light to react with oxygen and generate reactive oxygen species (ROS) in the skin. At low levels ROS are able to alter cell signalling and are thought to be the key mediators that reverse the signs of ageing. Dermatologists use this therapy to treat various characteristics of skin ageing such as fine/coarse wrinkles, mottled pigmentation, skin roughness and telangiectasia (small broken blood vessels near the surface of the skin). Initial clinical reports showed success; however, inconsistencies in patient outcomes provide impetus to improve characteristics of current treatment regimes including the PS, light sources, fluences and irradiances. As very little is known about the actual biological mechanism of PDR in human skin cells, the aim of this investigation was to first optimise a protocol using the PS, hypericin, activated with 3 different light sources. Hypericin, an extract from St Johns Wort, is a second generation PS that has many benefits such as low dark cytotoxicity, no carcinogenicity/mutagenicity, high quantum yield and can be activated by several wavelengths of light. We chose three light sources that emitted light within hypericin’s absorbance spectra: two lasers emitted light at 561nm and 632nm and lamps in a UVA transilluminator emitted a light range with a peak at 365nm. Cultured primary human fibroblasts were chosen as the cell model as they are an ideal representation of the dermal layer of the skin. Our results showed that low hypericin concentrations (0.25-0.5μM) at all three wavelengths caused an increase in cell viability. When this increase was investigated in relation to growth or cellular activity, growth curves showed that PDR with all 3 wavelengths had no effect on the cell proliferation rate. To confirm whether ROS was indeed occurring after the therapy, a ROS assay was performed. The yellow laser and UVA transilluminator, which emit light maximally absorbed by hypericin, were used. UVA served as the upper limit for ROS generation as this range of wavelengths is known to cause intracellular ROS. Yellow laseractivated hypericin resulted in a non-significant increase in intracellular ROS which was less than the levels in fibroblasts with UVA activated hypericin. This confirms that PDR using hypericin does generate ROS. As migration is considered inverse to collagen production and increased collagen is a main objective of skin rejuvenation, we studied fibroblast migration after PDR. To assess fibroblast migration in response to yellow laser light activation of hypericin, a scratch assay was used. This PDR protocol showed that migration was significantly slowed after treatment. Our proposal is that our PDR protocol with yellow laser light decreases migration diverting energy to producing collagen.

Background: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4-8% of cases. N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP) is a ubiquitous tetrapeptide with antifibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin converting enzyme inhibitors (ACEI), which increase Ac-SDKP levels with antifibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on AcSDKP and fibrosis in human tissues. Objective: To systematically review the effects of ACEIs on Ac-SDKP levels in human tissues. Methods: We searched five electronic databases (1996-2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.

This quantitative and qualitative study investigates the type and quality of health care and conditions of imprisonment that prevailed in some South African prisons in the late 1980s. It was inspired by political activists who were incarcerated, yet despite, or because of, the harsh conditions in prison persisted with their struggle for human rights. Appeals for the improvement of prison conditions which they submitted to the authorities are unique primary source documents. By implication, this survey adds value to their cause, for several issues examined in it had already been raised while they were in prison. With most information on prisons restricted until 1992, there was no body of literature on South African prison health care to review. Instead, Chapter 1 outlines the historical background of imprisonment in South Africa and key penal legislation. It also deals with events like the Biko affair which, in the recent past, affected the medical profession, the response of professional organisations to these events, and the national and international repercussions. Chapter 2 on the methodology describes the study design, data collection process and the limitations of the survey. Numerous attempts to interview District Surgeons and visit prisons were fruitless, consequently reducing the intended scope of the primary research. Because these external limitations affected the study design, they are discussed under methodology. A semi-structured questionnaire was developed to collect information about health care while imprisoned during the States of Emergency ( 1986-1990). Interviews based on this questionnaire were conducted with 123 ex-detainees from the Eastern and Western Cape. The results of the study are presented in Chapter 3, both quantitative, in the breakdowns of the data relating to each of the 14 questions, and qualitative, in the tables which reflect individual experiences and comments. The significance of these results is examined in the discussion in Chapter 4, backed by other supportive evidence. It begins by sketching general conditions of imprisonment, using unsolicited information from the interviewees, and proceeds to discuss health care services as they pertained during the study period. Many points of discussion also draw on the seven Case Reports and the report on North End Prison, Port Elizabeth, which have been added as an appendix to that chapter. The research indicates a disregard for the well-being of and failure to provide adequate health care for individuals at the mercy of detaining authorities. This situation was compounded by collusion among the forces of law and order and District Surgeons, and a scant response by academics and professional organisations to problems associated with imprisonment, isolation and torture. In the conclusion, Chapter 5, strategies for improving prison health care are explored. They are based on current national and international literature, policy and practice. The main proposals for reform are then summarised in the recommendations in Chapter 6. These range from revising legislation so as to accord with the constitutional rights of prisoners to addressing the training and attitudes of personnel, establishing health care standards and auditing mechanisms, and creating a more open prison system.