A qualitative and quantitative magnetic resonance diffusion study investigating the pathogenesis of cryptococcal-induced visual loss.

Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.Background: Cryptococcal induced visual loss is common and increasingly becoming a debilitating consequence in survivors of cryptococcal meningitis (CM). Conflicting reports of the optic neuritis and papilloedema models of visual loss have delayed the introduction of effective interventional strategies for prevention and treatment of visual loss in CM. Qualitative and quantitative diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) of the optic nerves have proven useful in the examination of the microstructure of the optic nerve especially in optic neuritis. Its application has been extrapolated to other optic nerve disorders such as ischaemic optic neuropathy and glaucoma. The aim of this study is to elucidate the pathogenesis of cryptococcal-induced visual loss using diffusion imaging of the optic nerve as an investigational tool. Method: Full ethical approval was obtained from the Greys Hospital, Department of Health and University of KwaZulu Natal Ethics Committees. Reliable and reproducible optic nerve diffusion techniques were first developed and optimized on 29 healthy volunteers at Greys Hospital, Neurology and Radiology departments using a Philips 1.5 Tesla Gyroscan. Informed consent was also obtained from 95 patients suffering from CM (≥18 yrs. of age), 14 patients with papilloedema and 14 patients with optic neuritis from other causes, recruited from Greys and Edendale Hospitals. Patients underwent full neuro-ophthalmological assessments, CSF examination, haematological workup, CD4 count, (viral load for some), electrophysiological assessment of vision [Visual evoked potential (VEP) and Humphreys visual fields (HVF)], Magnetic Resonance Imaging (MRI) scan of the brain and orbits and DWI and DTI of the optic nerves. Results and Discussion: Visual loss is common in CM, occurring in 34.6-48%. Optic neuritis was uncommon as evidenced by a lack of signal change and lack of enhancement within the optic nerve in all patients scanned. The peri-optic CSF space was not dilated and the optic nerve diameter was not increased regardless of CSF pressure and visual status. Swollen optic discs occurred in only 25% of patients whereas raised intracranial pressure (> 20cmCSF) was demonstrated in 69-71% of patients. Therefore visual loss could not be explained by papilloedema alone. The VEP P100 latency was shown to be a useful screening test for subclinical optic nerve disease in CM, but HVF was not. The optic nerve diffusion imaging used was reliable and reproducible and produced diffusion parameters equivalent to other investigators in the field. Neither optic nerve movement nor the CSF signal was demonstrated to impact significantly on optic nerve diffusion parameters. Optic nerve diffusion imaging did not demonstrate similarities between CM and papilloedema or optic neuritis regardless of CSF pressure or vision. Conclusion: The rarity of optic neuritis in CM and the disparity between papilloedema and visual loss together with the lack of support from diffusion studies suggest a 3rd mechanism of visual loss viz. the optic nerve compartment syndrome. Good clinical support is provided by a case report for this hypothesis that shows re-opening of the peri-optic CSF space and return of the peri-optic CSF signal on MRI with lowering of intracranial pressure and antifungal treatment

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Experience of the new seizure diary in the Free State and Northern Cape

Background: Epilepsy is a neurological disease affecting adults and children globally. A seizure diary is one of the self-management tools for tracking seizures. This study aims to ascertain the experience of a new seizure diary by persons completing the diary in the Free State and Northern Cape of South Africa.Methods: Adult patients with epilepsy attending Universitas Academic Hospital epilepsy clinic in Bloemfontein, clinics in Kimberley and the casualty department of Kimberley hospital (Robert Mangaliso Sobukwe hospital) received a new seizure diary. After using the diary for 6 months, participants (patients, relatives or caregivers) completed a questionnaire.Results: A total of 139 epilepsy patients received a new seizure diary; 67 previously diary-unexposed participants and 33 participants who had previous exposure to a seizure diary. The majority of participants, namely 91% of previously diary-unexposed and 84.9% of participants who had previous exposure to the seizure diary, understood the new seizure diary. Participants who had previous exposure to a seizure diary were predominantly very positive about the new diary because it had more information. However, 21.2% indicated that they preferred the old one because it was easier to complete.Conclusion: Patients, caregivers or relatives from both groups used the new seizure diary and provided important information about their experience with the new diary. Despite a few complaints about using the new diary, most participants who had previous exposure to a seizure diary preferred the new seizure diary.Contribution: This study explored participants’ opinions of the new seizure diary

The perceptions and attitudes of patients with epilepsy to the use of a seizure diary, South Africa

Background: Epilepsy is responsible for a significant proportion of the world’s disease burden, affecting around 50 million people globally. A seizure diary is a self-management tool for epilepsy focusing on self-monitoring, tracking seizures and other symptoms. This study aimed to determine the perceptions and attitudes to the seizure diary in patients with epilepsy in the Free State and Northern Cape of South Africa.Methods: This cross-sectional survey method included adult patients with epilepsy attending Universitas Academic Hospital Specialist Epilepsy Clinic in Bloemfontein and local clinics in Kimberley (City, Beaconsfield and Betty Gatsewe), as well as the casualty department of Kimberley hospital (Robert Mangaliso Sobukwe Hospital). The Kimberley patients were diary-unexposed, while the Bloemfontein patients were patients who had previous exposure to the seizure diary.Results: A total of 182 patients with epilepsy were recruited for the study, of whom 65 were patients who had previous exposure to the seizure diary, and 117 were unexposed. In the patients who had previous exposure to the seizure diary, 64 (98.5%) found the diary useful, but 15 (23.1%) reported having various challenges with using the seizure diary. Almost all of the patients who had previous exposure to the seizure diary, 64 (98.5%), were willing to continue to use the diary, while 112 (95.7%) of the diary-unexposed patients were also willing to use the diary.Conclusion: Information from some patients using the diary confirms various challenges with its use; however, most patients support the continued usage of the diary.

Current norms and practices in using a seizure diary for managing epilepsy: A scoping review

Background: Epilepsy is a chronic and debilitating condition affecting people of all ages in many nations. Healthcare practitioners look for effective ways to track patients’ seizures, and a seizure diary is one of the methods used. This scoping review sought to identify current norms and practices for using seizure diaries to manage epilepsy.Method: A scoping review was performed by screening relevant studies and identifying themes, categories and subcategories.Results: A total of 1125 articles were identified from the database; 46 full-text articles were assessed for eligibility, of which 23 articles were selected. The majority (48%) of the studies were prospective studies. The majority (65%) of the articles were studies conducted in the United States. The themes identified were types of seizure diaries used in clinical practice, contents and structure of a standardised seizure diary, the use and efficacy of seizure diaries in medicine and challenges relating to using a seizure diary for patient management.Conclusion: The study revealed that a seizure diary remains a relevant tool in managing epilepsy. The two forms of diaries in use are electronic and paper-based diaries. The high cost of data and the expensive devices required to access electronic diaries make it unsuitable in a resource-limited setting. Despite its disadvantages, imperfections and inadequacies, the paper-based diary is still relevant for managing patients with epilepsy in resource-limited settings.Contribution: This study reviewed the literature to find the current norms and practices in using seizure diaries. The benefits of the different formats were emphasised.

The neuromyelitis optica presentation and the aquaporin-4 antibody in HIV-seropositive and seronegative patients in KwaZulu-Natal, South Africa

CITATION: Bhigjee, A. I., et al. 2017. The neuromyelitis optica presentation and the aquaporin-4 antibody in HIV-seropositive and seronegative patients in KwaZulu-Natal, South Africa. Southern African Journal of HIV Medicine, 18(1):a684, doi:10.4102/sajhivmed.v18i1.684.The original publication is available at http://www.sajhivmed.org.za/Background: The association of the anti-aquaporin-4 (AQP-4) water channel antibody with neuromyelitis optica (NMO) syndrome has been described from various parts of the world. There has been no large study describing this association from southern Africa, an HIV endemic area. HIV patients often present with visual disturbance or features of a myelopathy but seldom both either simultaneously or consecutively. We report our experience of NMO in the era of AQP-4 testing in HIV-positive and HIV-negative patients seen in KwaZulu-Natal, South Africa. Methods: A retrospective chart review was undertaken of NMO cases seen from January 2005 to April 2016 in two neurology units serving a population of 7.1 million adults. The clinical, radiological and relevant laboratory data were extracted from the files and analysed. Results: There were 12 HIV-positive patients (mean age 33 years), 9 (75%) were women and all 12 were black patients. Of the 17 HIV-negative patients (mean age 32 years), 15 (88%) were women and 10 (59%) were black people. The clinical features in the two groups ranged from isolated optic neuritis, isolated longitudinally extensive myelitis or combinations. Recurrent attacks were noted in six HIV-positive patients and six HIV-negative patients. The AQP-4 antibody was positive in 4/10 (40%) HIV-positive patients and 11/13 (85%) HIV-negative patients. The radiological changes ranged from longitudinal hyperintense spinal cord lesions and long segment enhancing lesions of the optic nerves. Three patients, all HIV-positive, had tumefactive lesions with incomplete ring enhancement. Conclusion: This study confirms the presence of AQP-4-positive NMO in southern Africa in both HIV-positive and HIV-negative patients. The simultaneous or consecutive occurrence of optic neuritis and myelitis in an HIV-positive patient should alert the clinician to test for the AQP-4 antibody. It is important to recognise this clinical syndrome as specific therapy is available. We further postulate that HIV itself may act as a trigger for an autoimmune process.https://sajhivmed.org.za/index.php/hivmed/article/view/684Publisher's versio

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research