Clinical characteristics associated with mortality of COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

BACKGROUND: Over 130 million people have been diagnosed with Coronavirus disease 2019 (COVID-19), and more than one million fatalities have been reported worldwide. South Africa is unique in having a quadruple disease burden of type 2 diabetes, hypertension, human immunodeficiency virus (HIV) and tuberculosis, making COVID-19-related mortality of particular interest in the country. The aim of this study was to investigate the clinical characteristics and associated mortality of COVID-19 patients admitted to an intensive care unit (ICU) in a South African setting. METHODS AND FINDINGS: We performed a prospective observational study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to the ICU of a South African tertiary hospital in Cape Town. The mortality and discharge rates were the primary outcomes. Demographic, clinical and laboratory data were analysed, and multivariable robust Poisson regression model was used to identify risk factors for mortality. Furthermore, Cox proportional hazards regression model was performed to assess the association between time to death and the predictor variables. Factors associated with death (time to death) at p-value < 0.05 were considered statistically significant. Of the 402 patients admitted to the ICU, 250 (62%) died, and another 12 (3%) died in the hospital after being discharged from the ICU. The median age of the study population was 54.1 years (IQR: 46.0-61.6). The mortality rate among those who were intubated was significantly higher at 201/221 (91%). After adjusting for confounding, multivariable robust Poisson regression analysis revealed that age more than 48 years, requiring invasive mechanical ventilation, HIV status, procalcitonin (PCT), Troponin T, Aspartate Aminotransferase (AST), and a low pH on admission all significantly predicted mortality. Three main risk factors predictive of mortality were identified in the analysis using Cox regression Cox proportional hazards regression model. HIV positive status, myalgia, and intubated in the ICU were identified as independent prognostic factors. CONCLUSIONS: In this study, the mortality rate in COVID-19 patients admitted to the ICU was high. Older age, the need for invasive mechanical ventilation, HIV status, and metabolic acidosis were found to be significant predictors of mortality in patients admitted to the ICU.

Priority Setting as an Ethical Imperative in Managing Global Dialysis Access and Improving Kidney Care.

Priority-setting dilemmas arise when trade-offs must be made regarding the kinds of services that should be provided and to whom, thereby withholding other services from individuals or groups that could benefit from them. Currently, it is practically impossible for lower-income countries to provide dialysis for all patients with kidney failure; however, the fundamental premise of the human right to health, while acknowledging the current resource constraints, is the progressive realization of access to care for all. In this article we outline the rationale for priority setting, starting with the global goal of achieving universal health coverage, the prerequisites for fair and transparent priority setting, and discuss how these may apply to expensive care such as dialysis. Priority is inherently a value-laden process, and cannot be whittled down to technical considerations of clinical or cost effectiveness alone. Fair and transparent priority setting should originate from population health needs, be based on evidence, and be associated with ethical values or principles. This requires effective engagement with relevant stakeholders. Once policies are developed and implemented, good oversight is crucial to ensure accountability and to provide iterative feedback such that the goals of universal health coverage may be progressively realized.

Obesity and Other Nutrition Related Abnormalities in Pre-Dialysis Chronic Kidney Disease (CKD) Participants.

Chronic kidney disease (CKD) is increasing in sub-Saharan Africa. Undernutrition has been prevalent amongst end stage CKD patients, with limited data on the prevalence of obesity. The aim of this study was to assess the nutritional status of CKD patients using various methods sensitive to over and under-nutrition. Stage 3 to 5 CKD patients (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2) attending a pre-dialysis clinic in Cape Town, were enrolled. Exclusion criteria included infectious and autoimmune conditions. Sociodemographic, clinical and biochemical data were collected, and anthropometric measurements were performed. Dietary intake was measured with a quantified food frequency questionnaire (FFQ). Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. Seventy participants, with mean age of 41.8 ± 11.8 years, 52.9% females and 47.1% males were enrolled. Participants enrolled mainly had stage 5 kidney failure. Thirty percent were overweight (21) and 25 (36%) were obese, 22 (60%) of females were overweight and obese, while 13 (39.4%) of males were predominantly normal weight. Abdominal obesity was found in 42 (60%) of participants, mainly in females. Undernutrition prevalence was low at 3%. Dietary assessment showed a high sugar and protein intake. There was a high prevalence of overweight, obesity and abdominal obesity in CKD stage 35 patients, with unhealthy dietary intake and other nutritional abnormalities.

Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up.

INTRODUCTION: Ritual circumcision complicated by gangrene is a leading cause of penile loss in young men in South Africa. This deeply rooted cultural tradition is unlikely to be abolished. Conventional reconstructive techniques using free vascularised tissue flaps with penile implants are undesirable in this often socioeconomically challenged group because donor site morbidity can hinder manual labour and vigorous sexual activity might lead to penile implant extrusion. The psychosociological effects of penile loss in a young man are devastating and replacing it with the same organ is likely to produce the maximum benefit. METHODS: We first performed a cadaver-to-cadaver penile transplantation as preparation. After approval from the Human Research Ethics Committee was obtained, we recruited potential recipients. We screened the potential participants for both physical and psychological characteristics, including penile stump length, and emotional suitability for the procedure. A suitable donor became available and the penis was harvested. We surgically prepared the penile stump of the recipient and attached the penile graft. Immunosuppression treatment with antithymyocyte globulin, methylprednisolone, tacrolimus, mycophenolate mofetil, and prednisone were commenced. Tadalafil at 5 mg once per day was commenced after 1 week as penile rehabilitation and was continued for 3 months. We collected on quality-of-life scores (Short Form 36 version 2 [SF-36v2] questionnaires) before surgery and during follow-up and measured erectile function (International Index for Erectile Function [IIEF] score) and urine flow rates at 24 months post transplant. FINDINGS: The warm ischaemia time for the graft after removal was 4 min and the cold ischaemia time was 16 h. The surgery lasted 9 h. An arterial thrombus required urgent revision 8 h after the operation. On post operative day 6, an infected haematoma and an area of proximal skin necrosis were surgically treated. The recipient was discharged after 1 month and first reported satisfactory sexual intercourse 1 week later (despite advice to the contrary). The recipient reported regular sexual intercourse from 3 months after the operation. An episode of acute kidney injury at 7 months was reversed by reducing the tacrolimus dose to 14 mg twice per day. At 8 months after surgery, the patient had a skin infection with phaeohyphomycosis due to Alternaria alternata, which we treated with topical antifungal medication. Quality-of-life scores improved substantially after the operation (SF-36v2 mental health scores improved from 25 preoperatively, to 57 at 6 months and 46 at 24 months post transplant; physical health scores improved from 37 at baseline to 60 at 6 months and 59 at 24 months post-transplant). At 24 months, measured maximum urine flow rate (16·3 mL/s from a volume voided of 109 mL) and IIEF score (overall satisfaction score of 8 from a maximum of 10) were normal, showing normal voiding and erectile function, respectively. INTERPRETATION: Penile transplantation restored normal physiological functions in this transplant recipient without major complications in the first 24 months. FUNDING: Department of Health, Western Cape Government.

Ethical Challenges in the Provision of Dialysis in Resource-Constrained Environments.

The number of patients requiring dialysis by 2030 is projected to double worldwide, with the largest increase expected in low- and middle-income countries (LMICs). Dialysis is seldom considered a high priority by health care funders, consequently, few LMICs develop policies regarding dialysis allocation. Dialysis facilities may exist, but access remains highly inequitable in LMICs. High out-of-pocket payments make dialysis unsustainable and plunge many families into poverty. Patients, families, and clinicians suffer significant emotional and moral distress from daily life-and-death decisions imposed by dialysis. The health system's obligation to provide financial risk protection is an important component of global and national strategies to achieve universal health coverage. An ethical imperative therefore exists to develop transparent dialysis priority-setting guidelines to facilitate public understanding and acceptance of the realistic limits within the health system, and facilitate fair allocation of scarce resources. In this article, we present ethical challenges faced by patients, families, clinicians, and policy makers where dialysis is not universally accessible and discuss the potential ethical consequences of various dialysis allocation strategies. Finally, we suggest an ethical framework for use in policy development for priority setting of dialysis care. The accountability for reasonableness framework is proposed as a procedurally fair decision-making, priority-setting process.

Pharmacokinetics in stable kidney transplant recipients after conversion from twice-daily to once-daily tacrolimus formulations.

BACKGROUND: A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD. METHODS: This was an open-label, multicenter replicate design study in stable adult kidney transplant recipients (≥6 months posttransplantation) maintained on Tacrolimus BID. Patients underwent four sequential 14-day treatment periods of alternating Tacrolimus BID and QD (mg:mg conversion). Four 24-hour PK profiles were collected, one on the last day of each treatment period. Adverse events were also reported. RESULTS: A total of 60 of 69 patients completed all 4 PK profiles. Steady-state tacrolimus area under the curve from 0 to 24 hours and Cmin were comparable for both formulations, with treatment ratio means (90% confidence intervals) of 92.9% (89.8%-96.0%) and 90.9% (87.3%-94.6%), respectively (acceptance interval: 80%-125%). Both formulations were well tolerated, with renal function remaining stable over the 8-week period. There was a good correlation between area under the curve from 0 to 24 hours and Cmin for Tacrolimus QD and BID (r = 0.88 and 0.82, respectively). The relationship between these two parameters was also similar. CONCLUSIONS: The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring.

Relationship between serum protein and mortality in adults on long-term hemodialysis: exhaustive review and meta-analysis.

The aim of this exhaustive review and meta-analysis was to explore the relation among serum protein, inflammatory markers, and all-cause and cardiovascular mortalities in adult patients on maintenance hemodialysis. We searched the Medline, Science Citation Index, Academic Search Premier, Cochrane Library, and Embase electronic data bases. Data extraction and quality assessment were done independently by two reviewers and results were pooled using the random effects model. Cochran's Q was used to identify heterogeneity and a funnel plot was used for assessment of publication bias. A meta-analysis was performed on 38 studies (265 330 patients) reporting on serum proteins, inflammatory markers, and mortality. A significant inverse relation was found between serum albumin and all-cause (hazard ratio [HR] 0.7038, 95% confidence interval [CI] 0.6367-0.7781) and cardiovascular (HR 0.8726, 95% CI 0.7909-0.9628) mortalities, with a significantly stronger relation with all-cause mortality (P=0.0014). Pooled results for C-reactive protein showed a weak but significant direct relation with all-cause mortality (HR 1.0322, 95% CI 1.0151-1.0496), but there was not a significant relation between C-reactive protein and cardiovascular mortality (HR 1.0172, 95% CI 0.9726-1.0639). A high degree of heterogeneity was identified among studies especially in the case of all-cause mortality. An asymmetrical funnel plot for serum albumin is suggestive of publication bias. From the meta-analysis it is concluded that serum albumin showed a significant inverse relation with all-cause and cardiovascular mortalities but the relation between prealbumin and all-cause mortality was not significant. C-reactive protein showed a significant direct relation with all-cause mortality but not with cardiovascular mortality. The potential adverse effects of malnutrition and infections in relation to mortality highlight the need for continued treatment of infections and correction of malnutrition in patients on dialysis.

Skin cancer in renal allograft recipients--experience in different ethnic groups residing in the same geographical region.

Cancer is a recognized long-term complication of kidney transplantation. Skin cancer is the most common post-transplant malignancy in developed countries but information is limited on the nature of skin cancer in allograft recipients from developing countries followed up over an extended period. The records of all patients (n = 542) who had received kidney transplants (n = 623) at our institution over a 23-yr period were reviewed and those with skin cancer were identified. Demographic, clinical, and pathologic details were collected. After a mean follow up of 6.3 yr 11 (5.9%) white patients had skin cancer of whom nine (82%) were male. No non-whites had skin cancer. In white patients skin cancer accounted for 68% of all post-transplant malignancies. Squamous cell carcinoma was the most common malignant skin lesion and 84% of all lesions occurred in sun-exposed areas. Specific immunosuppression did not appear to influence the number of lesions or the interval from transplantation to cancer development. Patients responded well to treatment with no mortality related to the skin cancer. Skin cancer is relatively unique to patients of European origin.

The long-term outcome of kidney transplantation in patients under cyclosporine--a developing country experience.

The introduction of cyclosporine revolutionized the practice of solid organ transplantation. Although early studies showed better short-term results, the long-term benefits of cyclosporine appear to be more contentious. Our study investigated the outcome of sustained cyclosporine usage on patient and renal allograft survival in a developing country setting. All patients receiving primary renal transplants at our institution over a 23-yr period were included and data analysed for patient and graft survival rates using the Kaplan-Meier actuarial method. The patients receiving cyclosporine were compared with historical controls receiving conventional treatment. Early graft survival was superior in patients under cyclosporine but this benefit disappeared after the first year. There was no significant improvement in early patient survival in patients under cyclosporine but late survival was better in patients under conventional treatment. In our setting cyclosporine only improves early graft survival and does not have long-term benefit either on patient or graft survival.

Impact of age, gender and race on patient and graft survival following renal transplantation--developing country experience.

BACKGROUND: Optimising renal allograft survival is crucially important in developing countries because of limited resources to treat irreversible renal failure. However, although many factors can be manipulated to improve outcome, certain demographic factors are immutable in individual patients. The present study evaluated the impact of age, gender and race on the outcome of renal transplantation. METHODS: Relevant data were reviewed for 542 patients receiving primary renal allografts over a 23-year period. The survival of patients and grafts were calculated using the Kaplan-Meier method. Both univariate and multivariate analyses were used to determine the association between the demographic factors and patient and graft survival. RESULTS: Actuarial survival of both patients and grafts decreased with increasing age. The most striking differences were demonstrated when patients older than 40 years were compared with younger patients. However, when patient survival was censored for death with functioning grafts--a very important cause of graft loss--then actuarial graft survival improved with increasing age. There was no gender difference in graft survival, but female recipients of renal allografts had a higher mortality than their male counterparts. There were no racial differences in either patient or graft survival. CONCLUSIONS: Age is an important determinant of outcome after renal transplantation, but race is not. Gender does not influence graft survival, but females do have a higher overall mortality rate following renal transplantation at our centre.