A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Recommendations for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia.

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

Challenges around COVID-19 at a tertiary-level healthcare facility in South Africa and strategies implemented for improvement.

SARS-CoV-2 has resulted in a global pandemic within months following its initial detection. South Africa (SA), like many other countries, was not prepared for the impact this novel infection would have on the healthcare system. In this paper, the authors discuss the challenges experienced while facing COVID-19 at a tertiary-level institution in Gauteng province, SA, and the dynamic strategies implemented to deal with the epidemic.

Critical Care Society of Southern Africa adult patient blood management guidelines: 2019 Round-table meeting, CCSSA Congress, Durban, 2018.

The CCSSA PBM Guidelines have been developed to improve patient blood management in critically ill patients in southern Africa. These consensus recommendations are based on a rigorous process by experts in the field of critical care who are also practicing in South Africa (SA). The process comprised a Delphi process, a round-table meeting (at the CCSSA National Congress, Durban, 2018), and a review of the best available evidence and international guidelines. The guidelines focus on the broader principles of patient blood management and incorporate transfusion medicine (transfusion guidelines), management of anaemia, optimisation of coagulopathy, and administrative and ethical considerations. There are a mix of low-middle and high-income healthcare structures within southern Africa. Blood products are, however, provided by the same not-for-profit non-governmental organisations to both private and public sectors. There are several challenges related to patient blood management in SA due most notably to a high incidence of anaemia, a frequent shortage of blood products, a small donor population, and a healthcare system under financial strain. The rational and equitable use of blood products is important to ensure best care for as many critically ill patients as possible. The summary of the recommendations provides key practice points for the day-to-day management of critically ill patients. A more detailed description of the evidence used to make these recommendations follows in the full clinical guidelines section.

Challenges around COVID-19 at a tertiary-level healthcare facility in South Africa and strategies implemented for improvement

SARS-CoV-2 has resulted in a global pandemic within months following its initial detection. South Africa (SA), like many other countries, was not prepared for the impact this novel infection would have on the healthcare system. In this paper, the authors discuss the challenges experienced while facing COVID-19 at a tertiary-level institution in Gauteng province, SA, and the dynamic strategies implemented to deal with the epidemic

Intensive care medicine in rural sub-Saharan Africa.

We undertook an audit in a rural Ugandan hospital that describes the epidemiology and mortality of 5147 patients admitted to the intensive care unit. The most frequent admission diagnoses were postoperative state (including following trauma) (2014/5147; 39.1%), medical conditions (709; 13.8%) and traumatic brain injury (629; 12.2%). Intensive care unit mortality was 27.8%, differing between age groups (p < 0.001). Intensive care unit mortality was highest for neonatal tetanus (29/37; 78.4%) and lowest for foreign body aspiration (4/204; 2.0%). Intensive care unit admission following surgery (333/1431; 23.3%), medical conditions (327/1431; 22.9%) and traumatic brain injury (233/1431; 16.3%) caused the highest number of deaths. Of all deaths in the hospital, (1431/11,357; 12.6%) occurred in the intensive care unit. Although the proportion of hospitalised patients admitted to the intensive care unit increased over time, from 0.7% in 2005/6 to 2.8% in 2013/4 (p < 0.001), overall hospital mortality decreased (2005/6, 4.8%; 2013/14, 4.0%; p < 0.001). The proportion of intensive care patients whose lungs were mechanically ventilated was 18.7% (961/5147). This subgroup of patients did not change over time (2006, 16%; 2015, 18.4%; p = 0.12), but their mortality decreased (2006, 59.5%; 2015, 44.3%; p < 0.001).

Venous thromboembolism: prophylactic and therapeutic practice guideline.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed. This has resulted in unacceptable rates of morbidity and mortality. METHOD: The Southern African Society of Thrombosis and Haemostasis held a meeting to update the previous guideline and review new literature including guidelines from other societies. The following specialties were represented on the committees: anaesthetics, cardiology, clinical haematology, critical care, obstetrics and gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery and pulmonology. A draft document was presented at the meeting, which was then revised by consensus agreement. To avoid local bias, the guideline was adjudicated by recognised international external experts. RESULTS AND CONCLUSION: A concise, practical updated guideline for thromboprophylaxis and treatment in medical and surgical patients has been produced for South African conditions. It is hoped that this guideline will continue to improve anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Venous thromboembolism--prophylactic and therapeutic practice guideline.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed, which unfortunately results in unacceptable morbidity and mortality in a substantial number of patients. METHOD: The Southern African Society of Thrombosis and Haemostasis reviewed the available literature as well as guidelines from other societies. Specialties represented on the committees included anaesthetics, cardiology, clinical haematology, critical care, gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery, pulmonology and vascular surgery. A draft document was produced, which was revised by consensus agreement. To avoid local bias, the guidelines were adjudicated by recognised independent international external experts. RESULTS AND CONCLUSION. A concise, practical guideline for thrombo-prophylaxis and treatment in medical and surgical patients has been produced for South African conditions. These guidelines will hopefully lead to improved anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Long-term domiciliary oxygen therapy--the Johannesburg Hospital experience.

OBJECTIVES: To assess the clinical and demographic characteristics of patients attending an oxygen clinic, to assess the relevance of the current clinical criteria determining the need for domiciliary oxygen, to assess the cost-effectiveness of an oxygen clinic and to assess compliance with the oxygen prescription. DESIGN: Descriptive study with a retrospective review of data. SETTING: Tertiary-level academic hospital. SUBJECTS: All patients attending a newly established oxygen clinic. RESULTS: Data were analysed for 679 patients (361 male and 318 female), of whom 543 were ex- or current smokers, and 136 were non-smokers. Of the total number, 576 had chronic obstructive pulmonary disease. Oxygen was given to 425 patients and denied to 254. Forced expiratory volume in 1 second (FEV1) is probably not of value in determining requirement for oxygen as there was no correlation between severity of lung disease and partial arterial oxygen pressure (PaO2). There was also no correlation between PaO2 and litres of oxygen prescribed. Compliance with the oxygen prescription was 39%. Cost savings to the State from the oxygen that was not prescribed was in the region of R125,000 per month. CONCLUSIONS: Each patient should be assessed individually using clinical parameters to classify the disease severity and to assess the degree of tissue hypoxia. Oxygen clinics are of value and should be established more widely within each province. Compliance is suboptimal and continued follow-up to motivate patients to use the oxygen as prescribed should be instituted.

Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects.

OBJECTIVES: To describe the clinical manifestations of viral hemorrhagic fever, and to increase clinicians' awareness and knowledge of these illnesses. DESIGN: Retrospective study of the clinical and laboratory data and management of two cases of Ebola virus infection with key epidemiologic data provided. SETTING: Two tertiary care hospitals. PATIENTS: Two adult patients, the index case and the source patient, both identified as having Ebola, one of whom originated in Gabon. INTERVENTIONS: One patient was admitted to the intensive care unit. The other was managed in a general ward. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data are reported. One patient, a healthcare worker who contracted this illness in the course of her work, died of refractory thrombocytopenia and an intracerebral bleed. The source patient survived. Despite a long period during which the diagnosis was obscure, none of the other 300 contacts contracted the illness. CONCLUSIONS: Identification of high-risk patients and use of universal blood and body fluid precautions will considerably decrease the risk of nosocomial spread of viral hemorrhagic fevers.

Corticosteroids in life-threatening varicella pneumonia.

BACKGROUND: Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy. There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia. DESIGN AND METHODS: This was an uncontrolled retrospective and prospective study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996. Patient demographics, clinical and laboratory features, necessity for mechanical ventilation, and complications were reviewed. The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids. Patients with comorbid disease and those already taking immunosuppressive agents were excluded. Key endpoints included length of ICU and hospital stay and mortality. MEASUREMENTS AND RESULTS: Fifteen adult patients were evaluated, six of whom received corticosteroids in addition to antiviral and supportive therapy. These six patients demonstrated a clinically significant therapeutic response. They had significantly shorter hospital (median difference, 10 days; p<0.006) and ICU (median difference, 8 days; p=0.008) stays and there was no mortality, despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients (n=9) who did not receive corticosteroid therapy (86.5 vs 129.5; p=0.045). CONCLUSION: When used in addition to appropriate supportive care and early institution of antiviral therapy, corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia. The observations presented in this study are important and should form the basis for a randomized controlled trial, as no other relevant studies or guidelines are available.

Study of critically ill patients with systemic lupus erythematosus.

OBJECTIVES: To determine the presenting features, prognostic factors, course, and outcome of critically ill patients with systemic lupus erythematosus admitted to the intensive care unit (ICU). DESIGN: Retrospective patient record review. SETTING: Two academic teaching hospitals. PATIENTS: All patients with systemic lupus erythematosus admitted to the ICUs between January 1982 and July 1993. MEASUREMENTS AND MAIN RESULTS: There were 28 female and two male patients. Fifteen patients were white, 11 patients were black, and four patients were Asian. The median age was 29 yrs. The reasons for admission to the ICU were multifactorial. However, most patients were admitted for infective, renal, cardiac, or coagulation complications. Despite aggressive management, 16 (53%) patients died in the ICU or shortly after discharge. The median ICU survival rate (admission to death) was 22 days. The only pretreatment factor that predicted a poor outcome was the presence of renal involvement due to systemic lupus erythematosus. CONCLUSIONS: Our study suggests that patients with systemic lupus erythematosus admitted to an ICU often have florid disease manifestations with multifactorial reasons precipitating the admission. The prognosis for such patients is poor, particularly in the presence of renal involvement.

[The role of conformational changes in the functioning of brain Na,K-ATPase]. / O roli konformatsionnykh izmenenii v funktsionirovanii Na,K-ATFazy mozga.

In the experiments with enzyme preparations of Na,K-ATPase from normal brain tissue (NBT) and tumorous brain tissue (TBT) the following data were established: 1) the cooperativity of Na,K-ATPase with Na+ from NBT is temperature-dependent, the Hill coefficient (nH) at 37, 27.0-30.5 and 20-22 degrees C being 1.80 +/- 0.07, 1.30 +/- 0.09 and 1.10 +/- 0.08, respectively; the cooperativity of Na+ with Na,K-ATPase from TBT was absent; 2) the cooperativity for ouabain (nH-1.30 +/- 0.05) was revealed only in the case of Na-pump from TBT; 3) the protective effect of ATP against the inhibitory action of pCMB is temperature-dependent and differs significantly in enzyme preparations from NBT and TBT; 4) the parameters of the temperature inactivation of enzyme preparations at 45-52 degrees C, especially the change of entropy (delta S*) were different in the case of NBT and TBT; 5) a peptide fraction isolated from sheep brain differently inhibited the Na,K-ATPase from NBT and TBT. In conclusion, these data demonstrate that there are significant differences in functioning of Na,K-ATPase from NBT and TBT, and that besides lipid-protein interactions the local domenic conformational changes in the enzyme molecule may play a definite role in these differences.

[Characteristics of cooperative binding of Na+ and K+ with Na+,K+-ATPase depending upon its oligomeric structure]. / Osobennosti kooperativnogo sviazyvaniia Na+ i K+ s Na+,K+-ATPazoi mozga v zavisimosti ot ee oligomernoi struktury.

It has been shown that the desensibilization of the enzymic preparations of Na+, K+-ATPase by urea, DS-Na, digitonin and CHAPS reduces differently the amount of alpha beta-protomer in the enzymic preparations and the Hill coefficients of Na+ and K+. The factors (urea, DS-Na) which cause a more pronounced decrease in the amount of beta-protomer reduce the nH of Na+ for Na+, K+-ATPase and nH of K+ for Na+, K+-ATPase and K+-pNPPase to unit. The analysis of the effects of ATP and pNPP indicates that ATP has a protective effect only in the case of urea and DS-Na, but this effect is not exerted by pNPP (nonallosteric substrate). A conclusion is drawn that cooperative interactions of Na+, K+-ATPase from the brain with Na+ require more higher level of the oligomeric structure of enzyme than cooperative interactions with K+. At the same time these cooperative interactions in the both cases need subunits interactions in the protomer and interactions between cation sites with relatively high affinity.

[Prostaglandin E2 as a lipophilic allosteric modulator of the Na pump]. / Prostaglandin E2 kak lipofil'nyi allostericheskii moduliator Na-nasosa.

Curves of inhibition of rat brain Na, K-ATPase and K-pNPPase by prostaglandin E2 (PGE2) showed a sigmoidal shape with nH for PGE2 of 1.4 +/- 0.1 and 1.3 +/- 0.1, respectively. The desensitization of the enzymes with 0.25 M urea (4 degrees, 15 min) caused a loss of their cooperative interaction with PGE2. 2.0 mM PGE2 shifts the temperature break in the Arrhenius plots for the ATPase from 19.8 degrees to 23 degrees and simultaneously increased the Ea below the break by 9.5 kcal/mol. After treatment of the ATPase with phospholipase A2 PGE2 showed no cooperative interaction with the enzyme. Modulation of membrane enzymes by means of the surrounding lipid phasic state appears to be the general mechanism of their indirect allosteric regulation.