Low mortality of people living with diabetes mellitus diagnosed with COVID-19 and managed at a field hospital in Western Cape Province, South Africa.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was declared an international pandemic by the World Health Organization in March 2020. Throughout the pandemic, the association between diabetes mellitus (DM) and more severe COVID-19 has been well described internationally, with limited data, however, on South Africa (SA). The role of field hospitals in the management of patients with COVID-19 in SA has not yet been described. OBJECTIVES: To describe the mortality and morbidity of people living with DM (PLWD) and comorbid COVID-19, as well as to shed light on the role of intermediate facilities in managing DM and COVID-19 during the pandemic. METHODS: This is a single-centre cross-sectional descriptive study that included all patients with confirmed COVID-19 and pre-existing or newly diagnosed DM (of any type) admitted to the Cape Town International Convention Centre (CTICC) Intermediate Care Bed Facility from June 2020 to August 2020. This study presents the profile of patients admitted to the CTICC, and reports on the clinical outcome of PLWD diagnosed with COVID-19, and additionally determines some associations between risk factors and death or escalation of care in this setting. RESULTS: There were 1 447 admissions at the CTICC, with a total of 674 (46.6%) patients who had confirmed DM, of whom 125 (19%) were newly diagnosed diabetics and 550 (81%) had pre-existing DM. Included in this group were 57 referrals from the telemedicine platform - a platform that identified high-risk diabetic patients with COVID-19 in the community, and linked them directly to hospital inpatient care. Of the 674 PLWD admitted, 593 were discharged alive, 45 were escalated to tertiary hospital requiring advanced care and 36 died. PLWD who died were older, had more comorbidities (specifically chronic obstructive pulmonary disease, congestive cardiac failure and chronic kidney disease) and were more likely to be on insulin. CONCLUSIONS: In a resource-limited environment, interdisciplinary and interfacility collaboration ensured that complicated patients with DM and COVID-19 were successfully managed in a field hospital setting. Telemedicine offered a unique opportunity to identify high-risk patients in the community and link them to in-hospital monitoring and care. Future studies should explore ways to optimise this collaboration, as well as to explore possibilities for early identification and management of high-risk patients.

Addison's disease associated with hypokalemia: a case report.

BACKGROUND: Primary adrenal insufficiency (Addison's disease) is a rare medical condition usually associated with hyperkalemia or normokalemia. We report a rare case of Addison's disease, coexisting with hypokalemia, requiring treatment. CASE PRESENTATION: In this case, a 42-year-old man was admitted to the intensive care unit with a history of loss of consciousness and severe hypoglycemia. His blood tests showed metabolic acidosis, low concentrations of cortisol 6 nmol/L (normal 68-327 nmol/L), and high plasma adrenocorticotropic hormone 253 pmol/L (normal 1.6-13.9 pmol/L), and he was diagnosed with primary adrenal insufficiency. Surprisingly, his serum potassium was low, 2.3 mmol/L (normal 3.5-5.1 mmol/L), requiring replacement over the course of his admission. Computed tomography scan of the adrenal glands showed features suggestive of unilateral adrenal tuberculosis. Investigations confirmed renal tubulopathy. The patient responded favorably to cortisol replacement, but never required fludrocortisone. CONCLUSIONS: Coexistence of hypokalemia with Addison's disease is unusual. We recommend investigation of the cause of hypokalemia in its own right, if it occurs with primary adrenal insufficiency.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Clinical management of COVID-19: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has presented clinicians with an enormous challenge in managing a respiratory virus that is not only capable of causing severe pneumonia and acute respiratory distress syndrome, but also multisystem disease. The extraordinary pace of clinical research, and particularly the surge in adaptive trials of new and repurposed treatments, have provided rapid answers to questions of whether such treatments work, and has resulted in corticosteroids taking centre stage in the management of hospitalised patients requiring oxygen support. Some treatment modalities, such as the role of anticoagulation to prevent and treat potential thromboembolic complications, remain controversial, as does the use of high-level oxygen support, outside of an intensive care unit setting. In this paper, we describe the clinical management of COVID-19 patients admitted to Groote Schuur Hospital, a major tertiary level hospital at the epicentre of South Africa's SARS-CoV-2 epidemic during its first 4 months.

Diabetes mellitus and COVID-19: A review and management guidance for South Africa.

This article reviews the association between diabetes mellitus (DM) and COVID-19. We report on the convergence of infectious diseases such as coronavirus infections and non-communicable diseases including DM. The mechanisms for the interaction between COVID-19 and DM are explored, and suggestions for the management of DM in patients with COVID-19 in South Africa are offered.

Diabetes mellitus and COVID-19: A review and management guidance for South Africa

This article reviews the association between diabetes mellitus (DM) and COVID-19. We report on the convergence of infectious diseases such as coronavirus infections and non-communicable diseases including DM. The mechanisms for the interaction between COVID-19 and DM are explored, and suggestions for the management of DM in patients with COVID-19 in South Africa are offered

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa

The COVID-19 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals.

BACKGROUND: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population. METHODS: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system. RESULTS: Sixty seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6-10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0-686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age. CONCLUSION: This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l-1 vs. 37.49 (27.41-52.00) nmol*min*l-1; p=0.098, respectively], whereas the peak cortisol Cmax was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l-1 vs. 227.73 (200.10-280.52) nmol*min*l-1; p≤ 0.001, respectively], and peak cortisone Cmax was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement.

Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women.

BACKGROUND: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown. OBJECTIVE: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences. METHODS: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11ß-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures. RESULTS: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women. CONCLUSIONS: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.

Abnormal glucose metabolism in non-diabetic patients presenting with an acute stroke: prospective study and systematic review.

BACKGROUND: Non-diabetic patients presenting with an acute stroke often have hyperglycaemia. In most populations it is unknown whether the hyperglycaemia is transient and due to the acute stress response or whether it represents undiagnosed abnormal glucose metabolism. AIM: To evaluate the prevalence and predictors of persistent hyperglycaemia in non-diabetic patients with an acute stroke. DESIGN: Prospective observational study. METHODS: Non-diabetic patients over 40 years old with an acute stroke were enrolled over a 2-year period. On admission patients were evaluated with an HbA(1c) and a 75 g oral glucose tolerance test (OGTT). The OGTT was repeated 3 months later. A meta-analysis was performed to interpret our results in the context of published data. RESULTS: One hundred and seven patients were analysed. On admission 26 (24%) patients had diabetes, 39 (37%) had impaired glucose tolerance and 42 (39%) had normal glucose tolerance. Forty-four (68%) patients with hyperglycaemia on admission were re-investigated at least 3 months after discharge. Of these, 6 (14%) had diabetes, 12 (27%) had impaired glucose tolerance and 26 (59%) had normal glucose tolerance. A 2-h post-load glucose value >or=10 mmol/l predicted persistent hyperglycaemia with 72.2% sensitivity, 65.4% specificity and a positive predictive value and negative predictive value of 59.1 and 77.3%, respectively. A meta-analysis of prevalence data of impaired glucose metabolism in non-diabetic individuals 3 months after having had an acute stroke revealed a combined prevalence of 58% (95% confidence interval 25.4-90.5%). CONCLUSION: In this study hyperglycaemia in the setting of an acute stroke was transient in the majority of patients.

Prescribing insulin in type 1 diabetes mellitus: an update for general practitioners

The pancreas in a non-diabetic patient constantly secretes a small amount of insulin (basal secretion). After meals; a larger amount of insulin is secreted (bolus secretion) to cope with the increased blood glucose that occurs following a meal. The goal of insulin therapy in diabetics is to mimic this secretion pattern to provide enough insulin throughout a 24-hour period to meet the basal requirements and to deliver higher boluses of insulin to meet the glycaemic effect of meals. To achieve good diabetes control; an individually tailored insulin treatment regimen is required

The mycosins of Mycobacterium tuberculosis H37Rv: a family of subtilisin-like serine proteases.

There is little information regarding the role of proteolysis in Mycobacterium tuberculosis and no studies on the potential involvement of proteases in the pathogenesis of tuberculosis. We identified five M. tuberculosis genes (mycP1-5) that encode a family of serine proteases (mycosins-1 to 5), ranging from 36 to 47% identity. Each protein contains a catalytic triad (Asp, His, Ser) within highly conserved sequences, typical of proteases of the subtilisin family. These genes are also present in M. bovis BCG and other virulent mycobacteria, but only one homologue (mycP3) was detected in M. smegmatis. The mycosins have N-terminal signal sequences and C-terminal transmembrane anchors, and the localisation of the mycosins to the membrane/cell wall was verified by Western blot analysis of heterologously expressed proteins in cellular fractions of M. smegmatis. In M. tuberculosis, all the mycosins were expressed constitutively during growth in broth. Mycosins-2 and 3 were also expressed constitutively in M. bovis BCG, but no expression of mycosin-1 was detected. Mycosin-2 was modified by cleavage in all three mycobacterial species. The multiplicity and constitutive expression of these proteins suggests that they have an important role in the biology of M. tuberculosis.