Computed tomography-derived fractional flow reserve (FFRCT) has no additional clinical impact over the anatomical Coronary Artery Disease - Reporting and Data System (CAD-RADS) in real-world elective healthcare of coronary artery disease.

AIM: To evaluate the impact of computed tomography-derived fractional flow reserve (FFRCT) compared to the anatomical Coronary Artery Disease - Reporting and Data System (CAD-RADS) in the elective assessment of coronary artery disease in real-world cardiology practise. MATERIALS AND METHODS: A retrospective review was undertaken of 1,239 coronary CT examinations from August 2018 to December 2019 with a minimum follow-up period of 1 year. Coronary disease was classified according to the CAD-RADS system. A non-occlusive ≥30% maximum diameter stenosis was considered eligible for FFRCT. Lesion-specific FFRCT and FFR were considered positive if ≤ 0.80. The patients were followed up using the hospital radiology information system and the electronic patient record. A positive outcome was defined by a subsequent invasive angiogram (ICA) showing disease requiring revascularisation or FFR ≤0.80 or a positive stress test or medical therapy for angina in CAD-RADS 4. RESULTS: Of the 1,145 analysable studies (mean follow up 618 ± 153 days) the incidence of a positive result was 7% with a 5.4% elective revascularisation rate. Two hundred and forty-five patients (CAD-RADS 2-4) had FFRCT. FFRCT reduced the accuracy of the CAD-RADS grade from 91% to 78.4% (p<0.001). In CAD-RADS 2, the accuracy is reduced from 99% to 90.7% (p=0.005), and in CAD-RADS 3 from 93.9% to 67.7% (p<0.001). In CAD-RADS 4, FFRCT increases accuracy from 69.4% to 75.5% (p=0.025), but 89.8% of FFRCT are positive and specificity is low (26.7%). CONCLUSION: In the present "real-world" practise, FFRCT does not improve standard radiological assessment of coronary disease graded by the CAD-RADS alone.

Cartilage decisively shapes the glenoid concavity and contributes significantly to shoulder stability.

PURPOSE: Glenohumeral joint injuries frequently result in shoulder instability. However, the biomechanical effect of cartilage loss on shoulder stability remains unknown. The aim of the current study was to investigate biomechanically the effect of two severity stages of cartilage loss in different dislocation directions on shoulder stability. METHODS: Joint dislocation was provoked in 11 human cadaveric glenoids for 7 different directions between 3 o'clock (anterior) and 9 o'clock (posterior). Shoulder stability ratio (SSR) and concavity gradient were assessed in three states: intact, 3 mm and 6 mm simulated cartilage loss. The influence of cartilage loss on SSR and concavity gradient was statistically evaluated. RESULTS: Both SSR and concavity gradient decreased significantly between intact state and 6 mm cartilage loss in every dislocation direction (p ≤ 0.038), except concavity gradient in 4 o'clock direction. Thereby, anterior-inferior dislocation directions were associated with the highest decrease in both SSR and concavity gradient of up to 59.0% and 49.4%, respectively, being significantly bigger for SSR compared with all other dislocation directions (p ≤ 0.040). Correlations between concavity gradient and SSR for pooled dislocation directions were significant in each separate specimen's state (p < 0.001). CONCLUSION: From a biomechanical perspective, articular cartilage of the glenoid contributes significantly to the concavity gradient, correlating strongly with the associated loss in glenohumeral joint stability. The biggest effect of cartilage loss is observed in the most frequently occurring anterior-inferior dislocation directions, suggesting that surgical interventions to restore cartilage's surface and concavity should be considered for recurrent shoulder dislocations in presence of cartilage loss.

Predictors of in-hospital mortality among HIV-positive patients presenting with an acute illness to the emergency department.

OBJECTIVES: Despite better access to antiretroviral therapy (ART) over recent years, HIV remains a major global cause of mortality. The present study aimed to identify predictors of in-hospital mortality among HIV-positive patients presenting to an emergency department (ED). METHODS: In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 07 July 2017 and 18 October 2018 were prospectively enrolled. Data were compared between participants who survived to hospital discharge and those who died. The data were further subjected to univariate and multivariate logistic regression analyses to determine variables that were associated with in-hospital mortality. RESULTS: Of a total of 1224 participants, the in-hospital mortality was 13.6% (n = 166). On multivariate analysis, respiratory rate > 20 breaths/min [odds ratio (OR) = 1.90, P = 0.012], creatinine > 120 µmol/L (OR = 1.97, P = 0.006), oxygen saturation < 90% (OR = 2.09, P = 0.011), white cell count < 4.0 × 109 /L (OR = 2.09, P = 0.008), ART non-adherence or not yet on ART (OR = 2.39, P = 0.012), Glasgow Coma Scale < 15 (OR = 2.53, P = 0.000), albumin < 35 g/L (OR = 2.61, P = 0.002), lactate > 2 mmol/L (OR = 4.83, P = 0.000) and cryptococcal meningitis (OR = 6.78, P = 0.000) were significantly associated with in-hospital mortality. CONCLUSIONS: Routine clinical and laboratory parameters are useful predictors of in-hospital mortality in HIV-positive patients presenting to the ED with an acute illness. These parameters may be of value in guiding clinical decision-making, directing the appropriate use of resources and influencing patient disposition, and may also be useful in developing an outcome prediction tool.

Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.

ERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation of the highly polymorphic ERAP1 has been implicated in autoimmune disease and cancer. To test this hypothesis and establish the role of ERAP1 in these disease areas, high affinity, cell permeable and selective chemical probes are essential. DG013A 1, is a phosphinic acid tripeptide mimetic inhibitor with reported low nanomolar affinity for ERAP1. However, this chemotype is a privileged structure for binding to various metal-dependent peptidases and contains a highly charged phosphinic acid moiety, so it was unclear whether it would display the high selectivity and passive permeability required for a chemical probe. Therefore, we designed a new stereoselective route to synthesize a library of DG013A 1 analogues to determine the suitability of this compound as a cellular chemical probe to validate ERAP1 as a drug discovery target.

Patterns of presentation and survival of HIV-infected patients admitted to a tertiary-level intensive care unit.

OBJECTIVES: Compared to other countires internationally, South Africa has the largest number of people living with HIV. There are limited data in developing countries on the outcomes of HIV-infected patients in the intensive care unit (ICU). The objectives of this study were to describe the pattern of presentation of these patients and to determine factors that may influence survival to ICU discharge. METHODS: The medical charts of 204 consecutive HIV-infected individuals who were admitted to the Charlotte Maxeke Johannesburg Academic Hospital adult general ICU during the calendar year 2017 were retrospectively reviewed. Relevant data were subjected to univariate and multivariate analysis. RESULTS: Two-hundred and four (22.6%) out of a total of 903 patients who were admitted to the ICU were HIV positive. Sepsis-related illnesses were the most common reason for ICU admission (n = 95; 46.6%), followed by post-operative care (n = 69; 33.8%) and non-sepsis-related illnesses (n = 40; 19.6%). The median length of stay in the ICU was 5 (interquartile range 2-9) days. ICU mortality was 33.3% (n = 68). On univariate analysis, age (P = 0.039), length of stay in the ICU (P = 0.040), primary diagnostic category (P < 0.05), sepsis acquired during the ICU stay (P = 0.012), inotrope/vasopressor administration (P < 0.001), mechanical ventilation (P < 0.001), haemodialysis (P = 0.001), CD4 cell count (P = 0.011), Acute Physiology and Chronic Health Assessment (APACHE) II score (P < 0.001) and Sequential Organ Failure Assessment (SOFA) score (P < 0.001) were significantly associated with mortality. CONCLUSIONS: Age, diagnostic category, sepsis acquired during the ICU stay, inotrope/vasopressor administration, mechanical ventilation, haemodialysis, CD4 cell count, APACHE II score, SOFA score and length of ICU stay were associated with ICU mortality in HIV-infected patients.

Silicosis and pulmonary tuberculosis in deceased female South African miners.

BACKGROUND: Implementation of South Africa's 2002 Mining Charter increased women's participation in underground mining. However, occupational lung diseases (OLDs) in female gold miners have not been studied. AIMS: To compare autopsy-diagnosed pulmonary silicosis, lymph gland silicosis (a precursor of pulmonary silicosis) and active pulmonary tuberculosis (PTB) in South African gold miners. METHODS: The law allows for autopsies on miners for OLD compensation. Information is stored on the Pathology Automation (PATHAUT) database. We selected records of deceased miners who had worked only in gold mines, started employment from 2002, and were autopsied between 2005 and 2015. Using descriptive statistics, we compared demographic and employment characteristics, and disease proportions by sex. RESULTS: The study comprised 847 gold miners: 68 women and 779 men. There were no statistically significant differences in proportions of autopsy-diagnosed pulmonary silicosis [3 (4%) in women and 54 (7%) in men], lymph gland silicosis [11 (16%) and 171 (22%)] or PTB [29 (43%) and 254 (33%)]. Age and employment duration in women and men with disease were similar. Most miners with pulmonary silicosis had started employment from 2003 [315 (77%)] and worked for under 10 years. CONCLUSION: It is important to report research findings by sex. Proportions of silicosis and PTB were comparable in women and men, suggesting similar exposures. Silicosis detection after short employment indicates inadequate dust control, particularly as most entered the industry after implementation of interventions to control silica dust in 2003.

Development of a two-step, non-probed multiplex real-time PCR for surveilling Vibrio anguillarum in seawater.

Vibrio anguillarum is an aggressive and halophilic bacterial pathogen most commonly originating from seawater. Vibrio anguillarum presence in fisheries and aquaculture facilities causes significant morbidity and mortality among aquaculture species primarily from haemorrhaging of the body and skin of the infected fish that eventually leads to death, collectively recognized as the disease vibriosis. This study served to develop a non-probe, multiplex real-time PCR assay to rapidly detect V. anguillarum presence in seawater. Specific primers targeting genes vah1, empA and rpoN of V. anguillarum were selected for multiplex reaction among 11 different primer sets and the extension step was eliminated. Primer concentration, denaturation time as well as annealing time and temperature of DNA amplification were optimized, thus reducing reaction duration. The two-step, non-probed multiplex real-time PCR set forth by this study detects as little as 3 CFU mL(-1) of V. anguillarum presence in sea water, without enrichment cultivation, in 70 min with molecular precision and includes melting curve confirmation.

The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel bone fractures, bone biomechanics, behavior, and egg production in free-range laying hens.

Keel fractures in the laying hen are the most critical animal welfare issue facing the egg production industry, particularly with the increased use of extensive systems in response to the 2012 EU directive banning conventional battery cages. The current study is aimed at assessing the effects of 2 omega-3 (n3) enhanced diets on bone health, production endpoints, and behavior in free-range laying hens. Data was collected from 2 experiments over 2 laying cycles, each of which compared a (n3) supplemented diet with a control diet. Experiment 1 employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to 1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77) compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment 1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although dietary treatment was successful in reducing the frequency of fractures by approximately 27% in Experiment 2, data from Experiment 1 indicated the diet actually induced a greater likelihood of fracture (odds ratio: 1.2) and had substantial production detriment. Reduced keel breakage during Experiment 2 could be related to changes in bone health as n3-supplemented birds demonstrated greater load at failure of the keel, and tibiae and humeri that were more flexible. These results support previous findings that n3-supplemented diets can reduce fracture likely by increasing bone strength, and that this can be achieved without detriment to production. However, our findings suggest diets with excessive quantities of n3, or very high levels of C20/22, may experience health and production detriments. Further research is needed to optimize the quantity and type of n3 in terms of bone health and production variables and investigate the potential associated mechanisms.

Preventable suicides involving medicines: A systematic case series of coroners' reports in England and Wales.

Background: In England and Wales coroners have a duty to write a report, called a Prevention of Future Deaths report or PFD, when they believe that actions should be taken to prevent future deaths. Coroners send PFDs to individuals and organisations who are required to respond within 56 days. Despite the increase in mental health concerns and growing use of medicines, deaths reported by coroners that have involved medicine-related suicides had not yet been explored. Therefore, this study aimed to systematically assess coroners' PFD reports involving suicides in which a medicine caused or contributed to the death to identify lessons for suicide prevention. Methods: Using the Preventable Deaths Tracker database (https://preventabledeathstracker.net/), 3037 coroners' PFD reports in England and Wales were screened for eligibility between July 2013 and December 2019. Reports were included if they involved suicide or intentional self-harm and prescribed or over-the-counter medication; illicit drugs were excluded. Following data extraction, descriptive statistics, document and content analysis were performed to assess coroners' concerns and the recipients of reports. Results: There were 734 suicide-related coroner reports, with 100 (14%) reporting a medicine. Opioids (40%) were the most common class involved, followed by antidepressants (30%). There was wide geographical variation in the writing of reports; coroners in Manchester wrote the most (18%). Coroners expressed 237 concerns; the most common were procedural inadequacies (14%, n = 32), inadequate documentation and communication (10%, n = 22), and inappropriate prescription access (9%, n = 21). 203 recipients received the PFDs, with most sent to NHS trusts (31%), clinical commissioning groups (10%), and general practices (10%), of which only 58% responded to the coroner. Conclusions: One in four coroner reports in England and Wales involved suicides, with one in seven suicide-related deaths involving a medicine. Concerns raised by coroners highlighted gaps in care that require action from the Government, health services, and prescribers to aid suicide prevention. Coroner reports should be routinely used and monitored to inform public health policy, disseminated nationally, and responses to coroners should be transparently enforced so that actions are taken to prevent future suicides.

Clinical management and innovation in fracture nonunion.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture nonunion. Nonunion is generally believed to develop due to inadequate fixation, underlying host-related factors or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of nonunion. AREAS COVERED: This review provides a detailed description of nonunion from a clinical perspective including state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical and infection research fields are presented including the latest in smart implants, osteoinductive materials and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis and treatment of nonunion. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of nonunion causes and correlations, leading to the development of more effective treatments.

Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study.

BACKGROUND: A substantial proportion of patients with psoriasis do not respond, or lose initial response to tumour necrosis factor-α antagonists. One possible mechanism relates to subtherapeutic drug levels due to an immunogenic antibody response. OBJECTIVES: To investigate the association between serum adalimumab and etanercept levels, antidrug antibody levels and clinical response in a cohort of patients with psoriasis using a commercially available enzyme-linked immunoassay. METHODS: In a single-centre cohort of 56 adults with chronic plaque psoriasis initiated on adalimumab or etanercept monotherapy between 2009 and 2011, drug and antidrug antibody levels were measured at the patients' routine clinic reviews (4, 12 and 24 weeks of treatment and the last available observation). Patients' responses at 6 months were stratified into responders [75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) or Physician's Global Assessment score of 'clear' or 'nearly clear'] and nonresponders (failure to achieve PASI 50). RESULTS: After 4 weeks, adalimumab levels were significantly higher in responders compared with nonresponders (P = 0·003) and these higher levels were sustained at 12 and 24 weeks. Anti adalimumab antibodies were detected in 25% of nonresponders (two of eight patients, average 22·5 weeks' follow-up) and none of the responders (n = 23, average 26·1 weeks' follow-up). There was no significant association between etanercept levels and clinical response at 4 weeks (P = 0·317) and no antietanercept antibodies were detected. Lack of serum trough levels may have resulted in underestimation of the prevalence of antidrug antibodies. CONCLUSIONS: Early adalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response and potentially reduce drug exposure (and associated cost) with earlier review of treatment in those with low levels. No conclusions about the value of etanercept drug monitoring can be made due to the paucity of data. Larger studies are now required to assess the clinical utility and cost-effectiveness of these assays in personalizing therapy in psoriasis.

Clinical features and outcomes of patients with myasthenia gravis admitted to an intensive care unit: A 20-year retrospective study.

Background: There are limited data on the clinical characteristics and outcomes of patients with myasthenia gravis (MG) admitted to the intensive care unit (ICU) at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Objectives: The aim was to study the clinical characteristics and outcomes of patients with MG admitted to the CMJAH over two decades. Methods: A retrospective study was undertaken of patients with MG admitted to the multidisciplinary ICU of CMJAH over a 20-year period, from 1998 to 2017. Demographic data, clinical features, management and outcomes of patients were assessed and reviewed from the case records. Results: Thirty-four patients with MG were admitted to the ICU during this period: 24 female and 10 male. The mean age ± SD was 37.4 ± 13.0 years, with a range of 16 - 66 years. Four patients were human immunodeficiency virus (HIV)-positive. The mean length of stay (LOS) in ICU was 10.6 ± 20.1 days, ranging from 1 to 115 days. Two patients were diagnosed with MG in the ICU after failure to wean from the ventilator. Overall, 22 patients were intubated and ventilated on admission. Morbidities included self-extubation, aspiration pneumonia and iatrogenic pneumothorax. History of thymectomy was present in 12 patients. The treatments received for MG included pyridostigmine (73.5%), corticosteroids (55.9%), azathioprine (35.3%), plasmapheresis (26.5%) and intravenous immunoglobulin (8.8%). The overall mortality in the ICU was 5.9%. Conclusion: MG is a serious disorder with considerable morbidity and mortality. It is, however, a potentially manageable disease, provided that appropriate ICU resources are available. Contributions of the study: This study provides further insight into the characteristics and outcomes of myasthenia gravis patients in ICU, within a South African context.

Assessing housing exposures and interventions that impact healthy cities: a systematic overview of reviews.

AIM: There are direct links between housing and health. However, there is a lack of systematic reviews that bring together the evidence to outline the health impacts of exposures in housing and housing interventions. This article aims to address this gap by synthesising systematic reviews on the themes of housing exposures and interventions. METHODS: We searched four databases: Scopus (Elsevier), PsycINFO (OvidSP), Science Citation Index and Social Science Citation Index (Web of Science Core Collection), and the Sociology Collection (Proquest). We used keywords related to 'health' and 'city*' and included all types of reviews. We extracted data into a predesigned extraction form and synthesised information narratively. RESULTS: 745 articles were identified and screened, of which 256 reviews were included and 16 (6%) related to housing. All reviews related to housing exposures found that poor housing, including crowding, coldness, dampness, mould, and indoor air pollution had a negative impact on health. Most reviews found that housing interventions such as housing refurbishment, heating, and energy efficiency interventions positively impacted health outcomes. An online toolkit was developed to disseminate and communicate this research: https://www.healthycitiescommission.org/toolkit/. CONCLUSION: Governments have a pivotal role in addressing health issues related to housing interventions and exposures in housing. This includes interventions through building regulations following international guidance and financial assistance to encourage housing modifications that will improve health.

Fear, anxiety, and production in laying hens with healed keel bone fractures.

For laying hens, the immediate aftermath and healing period of a keel fracture (KF) is characterized by reduced ability to perform species-specific behavior, access resources, and pain. However, the longer-term impacts, once the fracture is completely healed, are less clear. As well as acute pain and behavioral changes, a negative experience can shape future responses to putatively threatening stimuli, raising future fear, and anxiety levels during husbandry-related events. We aimed to determine whether hens that had previously sustained keel bone fractures, but were now outside of the peak age range for new fractures, showed higher fear and anxiety levels compared to intact hens. We also determined if healed keel bone fractures were associated with reduced production, changes in behavior and resource use. One hundred and fifty hens with a palpation score of 1 ( "KF") and 150 hens with a palpation score of 0 (keel fracture free, "KFF") were selected from a commercial farm at 63 wk of age and housed in 6 groups (3 × KF and 3 × KFF). We compared production (hen weight and feed consumption, egg quantity, quality and weight, floor eggs, shell thickness, and weight) and home pen behavior (behaviors and transitional movements) in both groups. Finally, we measured the responses of KF (n = 75) and KFF (n = 75) during tonic immobility, novel arena, and novel object tests. KF and KFF hens did not differ in their responses to the tonic immobility, novel arena, and novel object tests, nor were there differences between the 2 groups in home pen behavior and transitional movements. KFF birds were lighter and laid eggs with less eggshell membrane compared KF birds, but no differences were found between KF and KFF in any other production measures. We found no evidence that healed KFs were associated with detrimental welfare effects in laying hens, but further work is required to determine the mechanisms and implications of the lower body weight and egg shell membrane.

Assessing and comparing chest radiograph interpretation in the Department of Internal Medicine at the University of the Witwatersrand medical school, according to seniority.

Background: Chest radiographs are a common diagnostic tool in the internal medicine department, and correct interpretation is imperative for adequate patient management. Objectives: To determine the diagnostic accuracy of common pathologies in South Africa that are evident on chest radiographs, and to determine whether there are discrepancies according to different levels of qualification of doctors rotating through the internal medicine department, and which factors contribute to an accurate diagnosis. Methods: Fifteen chest radiographs with common pathologies were given to all doctors rotating through the Department of Internal Medicine at Chris Hani Baragwanath Academic Hospital, and they were asked to interpret them. Information pertaining to their experience, designation and confidence in chest radiograph interpretation was also obtained. Results: Diagnostic accuracy according to years of experience was as follows: 0 - 5 years 27.0%, 6 - 10 years 43.0%, and >10 years 47.9%. For different designations, accuracy was as follows: consultants 50.5%, registrars 40.9%, medical officers 36.4%, and interns 19.5%. Participants who were confident obtained a mean score of 39.4% and those who were not, a mean score of 31.6%. Conclusion: Chest radiographs are readily accessible and used daily in clinical practice in numerous facilities. An accurate diagnosis is important to provide quality healthcare. Improved training in interpretation for all, but especially for junior doctors, should be a priority in our training facilities. Study synopsis: What the study adds. This study tested the diagnostic accuracy with regard to common pathologies present on chest X ray by doctors rotating through, or stationed at the internal medicine department at an academic hospital. Implications of the findings. Interpretation of chest X-rays was generally poor but the study did find that this improves with experience and confidence in diagnostic ability. These findings are significant in that they indicate a need to implement improved teaching programs in radiological interpretation, especially at an undergraduate level.

Core competencies in critical care for general medical practitioners in South Africa: A Delphi study.

Background: Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. Objectives: To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. Methods: A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. Results: A final list of 153 core competencies in critical care was identified. Conclusion: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA. Contribution of the study: The study provides consensus on a list of core competencies in critical care that non-intensivist medical practitioners managing critically ill patients in healthcare settings in South Africa, especially where intensivists are not readily available, should have. The list can form the core content of training programmes aimed at improving critical care competence of general medical practitioners, and in this way hopefully improve the overall outcomes of critically ill patients in South Africa.

Guideline summary: appropriate use of tigecycline.

Tigecycline, the first of a new class of broad-spectrum antibiotics (the glycylcyclines), has been licensed in South Africa for the parenteral treatment of adult patients with complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs). This article serves as a summary of the guideline on the appropriate use of tigecycline, published in mid-2010 as a collaborative effort by representatives of the Association of Surgeons of South Africa, the Critical Care Society of Southern Africa, the Federation of Infectious Diseases Societies of Southern Africa, the South African Thoracic Society and the Trauma Society of South Africa.

Risk factors and outcomes of sepsis-associated acute kidney injury in intensive care units in Johannesburg, South Africa.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) has been shown to be a significant contributor to morbidity and mortality in both children and adults with critical illness. In sub-Saharan Africa, there is a lack of information on factors associated with development of SA-AKI and outcomes after intensive care unit (ICU) admission. OBJECTIVES: To assess the rate of SA-AKI, factors associated with its development, and predictors of mortality at 90 days in critically ill patients admitted to the ICU with sepsis. METHODS: This was a prospective observational study conducted at two of the biggest teaching hospitals in Johannesburg, South Africa, from 15 February 2016 to 15 February 2020. The study included consecutive patients with confirmed sepsis who were admitted to the ICU within 24 hours of admission to hospital. The primary outcome of the study was development of SA-AKI (defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria), and secondary outcomes were risk factors for SA-AKI and predictors of mortality at 90 days. Multivariate logistic regression analysis was employed to determine the factors associated with SA-AKI and 90-day mortality. RESULTS: In total, 327 critically ill patients with sepsis admitted to the ICUs were included in the study. The median (interquartile range) age was 39 (30 - 52) years, and 185 patients (56.6%) developed SA-AKI. Of these patients, blacks and whites comprised 91.0% and 6.1%, respectively, and the prevalent comorbidities were HIV/AIDS (19.3%), hypertension (14.2%) and diabetes mellitus (10.1%). Patients with SA-AKI were likely to be older and of male gender, and to have cardiovascular disease, malignancies, hypotension and a low serum albumin level. In multivariate analysis, the predictors of SA-AKI were age ≥55 years (odds ratio (OR) 2.43; 95% confidence interval (CI) 1.27 - 4.65), inotropic support (OR 3.61; 95% CI 2.18 - 5.96) and a low serum albumin level (OR 2.93; 95% CI 1.40 - 6.13). SA-AKI and need for inotropic support were respectively associated with 1.9-fold and 1.7-fold increased mortality at 90 days after ICU admission. CONCLUSION: SA-AKI was found to be frequent in this study in two tertiary hospital ICUs in Johannesburg, and the need for inotropic support predicted mortality after ICU admission.

Comminuted intraarticular calcaneal fractures: Multiplanar VA locked plating and interlocked nailing incorporate longitudinal strut and provide superior stability - a biomechanical cadaveric study.

Treatment of comminuted intraarticular calcaneal fractures remains controversial and challenging. The aim of this study was to investigate the biomechanical performance of three different methods for fixation of such fractures. Comminuted calcaneal fractures, including Sanders III AB fracture of the posterior facet and Kinner II B fracture of the calcaneocuboid joint (CCJ) articular calcaneal surface, were created in 18 human cadaveric lower legs by osteotomizing. The ankle joint, medial soft tissues and midtarsal bones along with their ligaments were preserved. The specimens were randomized to three groups for fixation with either (1) 2.7 mm variable-angle locking lateral calcaneal plate (Group 1), (2) 2.7 mm variable-angle locking anterolateral calcaneal plate in combination with one 4.5 mm and one 6.5 mm cannulated screws (Group 2), or (3) interlocking calcaneal nail with 3.5 mm screws in combination with three separate 4.0 mm cannulated screws (Group 3). All specimens were biomechanically tested to failure under axial loading in midstance foot position. Each test commenced with a quasi-static compression ramp from 50 to 200 N, followed by progressively increasing cyclic loading at 2 Hz. Starting from 200 N, the peak load of each cycle increased at a rate of 0.2 N/cycle. Interfragmentary movements were captured by motion tracking. In addition, mediolateral X-rays were taken every 250 cycles with a triggered C-arm. Böhler angle after 5000 cycles (1200 N peak load) increased significantly more in Group 1 compared to both other groups (P ≤ 0.020). Varus deformation of 10° between the calcaneal tuberosity and the lateral calcaneal fragments was reached at significantly lower number of cycles in Group 1 compared the other groups (P ≤ 0.017). Both cycles to 10° plantar gapping between the anterior process and the calcaneal tuberosity fragments, and 2 mm displacement at the CCJ articular calcaneal surface revealed no significant differences among the groups (P ≥ 0.773). From a biomechanical perspective, treatment of comminuted intraarticular calcaneal fractures using anterolateral variable-angle locking plate with additional longitudinal screws or interlocked nail in combination with separate transversal screws provides superior stability as opposed to lateral variable-angle locked plating only.

The optimal management of the patient with COVID-19 pneumonia: HFNC, NIV/CPAP or mechanical ventilation?

The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID-19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient. This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes. On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet-CPAP (continuous positive airway pressure) (although not widely available) may be superior to high-flow nasal cannula (HFNC) therapy or facemask non-invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces. In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.