Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with Type 2 diabetes with and without fatty liver.

To investigate the potential of therapies which reduce glucocorticoid action in patients with Type 2 diabetes we performed a randomized, double-blinded, placebo-controlled crossover study of acute glucocorticoid blockade, using the glucocorticoid receptor antagonist RU38486 (mifepristone) and cortisol biosynthesis inhibitor (metyrapone), in 14 men with Type 2 diabetes. Stable isotope dilution methodologies were used to measure the rates of appearance of glucose, glycerol, and free fatty acids (FFAs), including during a low-dose (10 mU·m⁻² ·min⁻¹) hyperinsulinemic clamp, and subgroup analysis was conducted in patients with high or low liver fat content measured by magnetic resonance spectroscopy (n = 7/group). Glucocorticoid blockade lowered fasting glucose and insulin levels and improved insulin sensitivity of FFA and glycerol turnover and hepatic glucose production. Among this population with Type 2 diabetes high liver fat was associated with hyperinsulinemia, higher fasting glucose levels, peripheral and hepatic insulin resistance, and impaired suppression of FFA oxidation and FFA and glycerol turnover during hyperinsulinemia. Glucocorticoid blockade had similar effects in those with and without high liver fat. Longer term treatments targeting glucocorticoid action may be useful in Type 2 diabetes with and without fatty liver.

High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa.

Background: High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). Objectives: To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. Methods: We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. Results: A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p<0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p<0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p<0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2 /FiO2 ) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p<0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Conclusion: Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome. Study synopsis: What the study adds. This study adds to the body of evidence demonstrating the utility of high-flow nasal oxygen (HFNO) in avoiding invasive mechanical ventilation (IMV) in patients with severe COVID-19 hypoxaemic respiratory failure, and shows that this utility remained consistent across different waves of the COVID-19 pandemic.Implications of the study. In resource-constrained settings, HFNO is a feasible non-invasive alternative to IMV and can be employed with favourable and consistent outcomes outside traditional critical care wards. It also confirms that the degree of gas exchange abnormality, and not pre-existing patient-related factors, circulating wave variant or provider experience, is the main predictor of HFNO failure.

Delirium in HIV-infected patients admitted to acute medical wards post universal access to antiretrovirals in South Africa.

BACKGROUND: Delirium is associated with increased mortality and length of hospital stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium among acute medical admissions in South Africa (SA), a developing country with universal antiretroviral therapy (ART) access and high burdens of tuberculosis (TB) and non-communicable disease. OBJECTIVES: To identify the prevalence of, risk factors for and outcomes of delirium in HIV-infected individuals in acute general medical admissions. METHODS: Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Wynberg hospitals, Cape Town, SA, were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method. RESULTS: The study included 1 182 acute medical admissions, with 318 (26.9%) HIV-infected. The median (interquartile range) age and CD4 count were 35 (30 - 43) years and 132 (61 - 256) cells/µL, respectively, with 140/318 (44.0%) using ART on admission. The prevalence of delirium was 17.6% (95% confidence interval (CI) 13.7 - 22.1) among HIV-infected patients, and delirium was associated with increased inpatient mortality. In multivariable logistic regression analysis, factors associated with delirium were age ≥55 years (adjusted odds ratio (aOR) 6.95 (95% CI 2.03 - 23.67); p=0.002), and urea ≥15 mmol/L (aOR 4.83 (95% CI 1.7 - 13.44); p=0.003), while ART use reduced risk (p=0.014). A low CD4 count, an unsuppressed viral load and active TB were not predictors of delirium; nor were other previously reported risk factors such as non-opportunistic acute infections or polypharmacy. CONCLUSIONS: Delirium is common and is associated with increased mortality in HIV-infected acute medical admissions in endemic settings, despite increased ART use. Older HIV-infected patients with renal dysfunction are at increased risk for inpatient delirium, while those using ART on admission have a reduced risk.

Prevalence and outcome of delirium among acute general medical inpatients in Cape Town, South Africa.

BACKGROUND: Delirium is a common, serious, underdiagnosed condition in medical and surgical inpatients with acute conditions. It is associated with increased risk of mortality and morbidity. Data of geriatric cohorts are largely limited to developed countries. OBJECTIVES: To describe prevalence, risk factors and outcomes of delirium among general medical patients admitted to two hospitals in Cape Town, South Africa. METHODS: This was a prospective cohort study of patients with acute conditions admitted to a general medical inpatient service in secondary- and tertiary-level public hospitals in the Metro West area of Cape Town. Patients ≥18 years of age were recruited daily from all acute medical admissions. Patients were excluded if they were aphasic or their Glasgow coma scale was <8/15. Delirium was diagnosed using the validated confusion assessment method (CAM) tool and performed by trained neuropsychologists. Demographic data were collected by a clinical team and short- and long-term mortality data were obtained using linkage analysis of hospitalised patients and routinely collected provincial death certification records. RESULTS: The median age of inpatients was 51 (interquartile range 36 - 65) years, 29% were HIV-infected and the overall prevalence of delirium was 12.3%. Multivariate predictors of delirium included the presence of an indwelling urinary catheter (odds ratio (OR) 4.47; confidence interval (CI) 2.43 - 8.23), admission with a central nervous system disease (OR 4.34; CI 2.79 - 7.90), pre-existing cognitive impairment (OR 3.02; CI 1.22 - 7.43) and immobility (OR 1.88; CI 1.01 - 3.51). HIV infection was not associated with increased risk of delirium. Delirium was associated with an increased risk of inhospital (delirium v. no delirium: 29% v. 12%; p<0.01) and 12-month (30% v. 20%; p<0.01) mortality, as well as increased length of hospital stay (7 days v. 5 days; p<0.01). CONCLUSIONS: In this cohort of medical inpatients (relatively young and with a high HIV prevalence) 1 of 8 (12.3%) patients was delirious. Delirium was associated with adverse outcomes. Delirium risk factors in this young cohort were similar to those in geriatric cohorts in developed countries, and neither HIV nor opportunistic infections increased risk.

Prolonged treatment of COVID-19 pneumonia with high-flow nasal oxygen: A story of oxygen and resilience.

The COVID-19 pandemic has placed significant strain on the oxygen delivery infrastructure of health facilities in resource-constrained health systems. In this case report, we describe a patient with severe COVID-19 pneumonia who was managed with high-flow nasal oxygen for 40 days, with an eventual successful outcome. We discuss the oxygen delivery infrastructure needed to offer this intervention, as well as the psychosocial impact on those undergoing treatment.

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.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

The development of hospital-based palliative care services in public hospitals in the Western Cape, South Africa.

With the recent approval of a South African (SA) National Policy Framework and Strategy for Palliative Care by the National Health Council, it is pertinent to reflect on initiatives to develop palliative care services in public hospitals. This article reviews the development of hospital-based palliative care services in the Western Cape, SA. Palliative care services in SA started in the non-governmental sector in the 1980s. The first SA hospital-based palliative care team was established in Charlotte Maxeke Johannesburg Academic Hospital in 2001. The awareness of the benefit of palliative care in the hospital setting led to the development of isolated pockets of excellence providing palliative care in the public health sector in SA. This article describes models for palliative care at tertiary, provincial and district hospital level, which could inform development of hospital-based palliative care as the national policy for palliative care is implemented in SA.

Sustained reduction in antibiotic consumption in a South African public sector hospital; Four year outcomes from the Groote Schuur Hospital antibiotic stewardship program.

BACKGROUND: Overuse of antibiotics has driven global bacterial resistance to the extent that we have entered a post-antibiotic era, where infections that were once easily treatable are now becoming untreatable. Efforts to control consumption have focused on antibiotic stewardship programmes (ASPs), aimed at optimising use. OBJECTIVE: To report antibiotic consumption and cost over 4 years from a public hospital ASP in South Africa (SA). METHODS: A comprehensive ASP comprising online education, a dedicated antibiotic prescription chart and weekly dedicated ward rounds was introduced at Groote Schuur Hospital, Cape Town, in 2012. Electronic records were used to collect data on volume and cost of antibiotics and related laboratory tests, and to determine inpatient mortality and 30-day readmission rates. These data were compared with a control period before the intervention. RESULTS: Total antibiotic consumption fell from 1 046 defined daily doses/1 000 patient days in 2011 (control period) to 868 by 2013 and remained at similar levels for the next 2 years. This was driven by reductions in intravenous antibiotic use, particularly ceftriaxone. Inflation-adjusted cost savings on antibiotics were ZAR3.2 million over 4 years. Laboratory tests increased over the same period with a total increased cost of ZAR0.4 million. There was no significant change in mortality or 30-day readmission rates. CONCLUSIONS: The effects of a comprehensive ASP on medical inpatients at a public sector hospital in SA were durable over 4 years, leading to a reduction in total antibiotic consumption without adverse effect. When increased laboratory costs were offset there was a net cost saving of ZAR2.8 million.

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

A point-prevalence survey of public hospital inpatients with palliative care needs in Cape Town, South Africa.

OBJECTIVES: To assess the need for palliative care among inpatients occupying acute beds in the public sector hospitals of the Cape Town Metropole. METHODS: A cross-sectional, contemporaneous, point-prevalence study was performed at 11 public sector hospitals in the Cape Town Metropole using a standardised palliative care identification tool. Data were collected on the socio-demographic characteristics, diagnoses, and prior and current care planning of patients. RESULTS: The case notes of 1 443 hospital inpatients were surveyed, and 16.6% were found to have an active life-limiting disease. The mean age of the group was 56 years. The diagnoses were cancer in 50.8%, organ failure in 32.5%, and HIV/tuberculosis in 9.6%. The greatest burden of disease was in the general medical wards, to which an overall 54.8% of patients meeting the requirements for palliative care were admitted. CONCLUSIONS: This study provides evidence for the need for palliative care services in public sector hospitals and in the health system as a whole. The young age of patients and the high prevalences of end-stage renal failure and HIV are unique, and the burden in the general medical wards suggests a focus for initial inpatient programmes.

Suicidal ideation and attempt among South African medical students.

International data reveal that medical students are at higher risk of attempting suicide than the general population. We aimed to determine the prevalence of suicidal ideation and attempt among South African medical students from three universities and identify key predisposing risk factors. Data were collected via a questionnaire to medical students on demographics, mental health history, depressive symptoms, suicidal ideation and attempt. A total of 874 medical students from three universities were enrolled. We found a high prevalence of suicidal ideation (32.3%) and suicidal attempt (6.9%), which is three times higher than the general age-appropriate South African population. Simple screening questionnaires can identify such students, enabling universities to provide targeted and improved support for at-risk students.

Twelve-month outcomes of patients admitted to the acute general medical service at Groote Schuur Hospital.

OBJECTIVES: Hospitalisation for medical illness has ongoing impact on individuals, healthcare services and society beyond discharge. This study's objective was to determine the 12-month mortality and functional outcomes of patients admitted to the acute medical service at Groote Schuur Hospital (GSH). METHODS: Follow-up, using the hospital records system and provincial death registry, together with telephonic interviews or home visits, was attempted for 465 medical inpatients admitted to GSH between 14 September and 16 November 2009. Functional outcomes were assessed using the Katz activities of daily living (ADL) score and Barthel index (BI). Outcome measures. The major study outcomes included: 12-month mortality (overall and unexpected), changes in functional status and pre- and post-admission employment rates. RESULTS: Inpatient mortality was 11%. At 12-month follow-up, 35% (145/415) were deceased and 30% (125/415) could not be traced; 38% (55/145) of deaths were considered expected and unexpected mortality was associated with age >40 years (p=0.02) and an admission urea >7.0 mmol/l (p=0.004). Katz ADL deteriorated in 15% (21/143) of interviewed patients and was associated with age >50 years (p=0.005); 23% (33/143) had improved Katz ADL associated with admission human immunodeficiency virus (HIV) (p=0.01), tuberculosis (TB) infection (p=0.05) and sepsis (p=0.02). Employment rates declined from 41% (59/145) pre-admission to 18% (26/145) at 12 months (p<0.001), with little increase in the number of persons receiving disability grants. Twenty per cent (29/145) of patients required hospital readmission and this was associated with ADL functional decline (p=0.01). CONCLUSIONS: There was a very high overall mortality of 42% in patients admitted to the general medical wards. Significant employment decline and readmission rates highlight the additional economic and societal burdens of hospitalisation due to medical illness in the survivors.

Concomitant HIV infection in newly diagnosed multiple myeloma patients is hard to recognise and should be tested for routinely in areas of high endemicity

Background. Over the past three decades much has changed in the treatment and outcomes of patients suffering concurrently from both multiple myeloma (MM) and HIV. While the prevalence of MM appears to be higher in HIV-positive individuals than in those who are uninfected, early recognition of patients suffering from both diseases is difficult and little information is available on their demographics and clinical presentation.Objective. To compare the presenting features of HIV-positive patients diagnosed with MM with those of HIV-negative patients.Methods. A single-centre, retrospective cohort study included 16 HIV-positive and 73 HIV-negative patients diagnosed with MM, in order to compare variables related to the clinical presentation of both conditions.Results. HIV-positive patients presented with MM at a significantly younger age, and had fewer osteolytic lesions, less renal impairment and lower neutrophil counts. Disease stage, gender, pathological fractures, bone marrow plasmacytosis, plasmacytomas and lymphocyte counts were comparable, emphasising the difficulty of identifying these patients. The HIV-positive patients had relatively high CD4 counts and a low prevalence of abnormal Freelite kappa/lambda ratios. All HIV-positive patients presented with paraproteins of the immunoglobulin G (IgG) type, implying a possible relationship between MM and an IgG response to HIV antigens.Conclusions. On the basis of our findings and literature on the treatment of both diseases, we suggest that HIV be tested for routinely in younger MM patients, especially in areas with a high prevalence of HIV. The integration of our results into the sparse knowledge on the role of HIV infection-related MM provides possible new insights into the interaction between these diseases

Concomitant HIV infection in newly diagnosed multiple myeloma patients is hard to recognise and should be tested for routinely in areas of high endemicity

Background. Over the past three decades much has changed in the treatment and outcomes of patients suffering concurrently from both multiple myeloma (MM) and HIV. While the prevalence of MM appears to be higher in HIV-positive individuals than in those who are uninfected, early recognition of patients suffering from both diseases is difficult and little information is available on their demographics and clinical presentation.Objective. To compare the presenting features of HIV-positive patients diagnosed with MM with those of HIV-negative patients.Methods. A single-centre, retrospective cohort study included 16 HIV-positive and 73 HIV-negative patients diagnosed with MM, in order to compare variables related to the clinical presentation of both conditions.Results. HIV-positive patients presented with MM at a significantly younger age, and had fewer osteolytic lesions, less renal impairment and lower neutrophil counts. Disease stage, gender, pathological fractures, bone marrow plasmacytosis, plasmacytomas and lymphocyte counts were comparable, emphasising the difficulty of identifying these patients. The HIV-positive patients had relatively high CD4 counts and a low prevalence of abnormal Freelite kappa/lambda ratios. All HIV-positive patients presented with paraproteins of the immunoglobulin G (IgG) type, implying a possible relationship between MM and an IgG response to HIV antigens.Conclusions. On the basis of our findings and literature on the treatment of both diseases, we suggest that HIV be tested for routinely in younger MM patients, especially in areas with a high prevalence of HIV. The integration of our results into the sparse knowledge on the role of HIV infection-related MM provides possible new insights into the interaction between these diseases

Acute hospitalisation needs of adults admitted to public facilities in the Cape Town Metro district.

INTRODUCTION: Public health care delivery in South Africa aims to provide equitable access at the most appropriate level of care. We studied to what extent the acute health care needs of adults admitted to public hospitals in the Cape Town Metropole were being appropriately met. METHODS: A retrospective study was conducted of the hospital records of adults admitted to medical beds in public hospitals in Cape Town between August and November 2008. Intensive care unit patients were not included. RESULTS: Of 802 beds in use, the estimated occupancy was at least 95%. The average time elapsed since admission was 7.9 days; 94.3% of medical admissions were acute; 45% were severely to critically ill on admission; and co-morbid disease was present in 78.1%. Of all admissions, 31.9% were HIV-positive, and 17% had active tuberculosis. At least 396 (51.6%) patients were deemed to have required specialist or subspecialist consultation to expedite appropriate care; 386 (50.3%) accessed the appropriate level of medical care required; 339 (44.2%) accessed a more sophisticated level of care than required; and 42 (5.5%) did not access an adequate level of care. CT scan and ultrasound accounted for 59% of all restricted tests done. CONCLUSIONS: Our findings support the plan to provide more primary care hospital facilities in the metropolitan area. Most patients needing specialised care are accessing such care, and most patients accessing a higher level of care than needed can be addressed by ensuring that they first access primary care and are referred according to protocols.

Paget's disease complicated by hydrocephalus and syringomyelia.

The authors report a case of Paget's disease involving the skull with the rare but severe complications of hydrocephalus and syringomyelia related to basilar impression. Complications of Paget's disease of the skull are briefly discussed and current treatment strategies outlined.