Resource tiered reviews – a provisional reporting checklist

AFJEM is committed to publishing review articles that will benefit acute care providers, independent of the resources available to them. As a result we have compiled a checklist aimed specifically at best evidence in the resource-restricted setting (Table 1). The aim is to guide authors in producing a report which is a combination between a clinical guideline and a systematic review. Best available evidence, using a transparent and systematic approach to find and evaluate relevant studies, is still key; but with additional focus on resource availability. In effect it will be more rigorous than a narrative review but less time-consuming than a systematic review or meta-analysis. In order to apply the content to different resource levels, authors are advised to start by describing the very best evidence available; then assume the resources for this level are not available and describe the next tier of evidence until all options are exhausted. For example, if we return to our patient with chest pain: the recommended treatment for a patient with STEMI is primary percutaneous coronary intervention; if this treatment is not available, then thrombolytics should be considered; if that is not available then antiplatelet therapy and anticoagulation should be used, and so on and so forth

A descriptive analysis of the effect of the national COVID-19 lockdown on the workload and case mix of patients presenting to a district-level emergency centre in Cape Town, South Africa

Background. The global COVID-19 pandemic caused many countries to institute nationwide lockdowns to limit the spread of the disease.Objectives. To describe the effect of the national COVID-19 lockdown in South Africa (SA) on the workload and case mix of patients presenting to a district-level emergency centre.Methods. The electronic patient tracking and registration database at Mitchells Plain Hospital, a district-level hospital in Cape Town, was retrospectively analysed. The 5-week lockdown period (27 March - 30 April 2020) was compared with a similar period immediately before the lockdown (21 February - 26 March). A comparison was also made with corresponding time periods during 2018 and 2019. Patient demographics, characteristics, diagnoses and disposition, as well as process times, were compared.Results. A total of 26 164 emergency centre visits were analysed (8 297 in 2020, 9 726 in 2019, 8 141 in 2018). There was a reduction of 15% in overall emergency centre visits from 2019 to 2020 (non-trauma 14%, trauma 20%). A 35% decrease was seen between the 2020 lockdown period and the 5-week period before lockdown (non-trauma 33%, trauma 43%), and the reduced number of visits stayed similar throughout the lockdown period. The median age increased by 5 years during the 2020 lockdown period, along with an 8% decrease in patients aged <12 years. High-acuity patients increased by 6% and the emergency centre mortality rate increased by 1%. All process times were shorter during the lockdown period (time to triage –24%, time to consultation –56%, time to disposition decision –29%, time in the emergency centre –20%).Conclusions. The SA national COVID-19 lockdown resulted in a substantial decrease in the number of patients presenting to the emergency centre. It is yet to be seen how quickly emergency centre volumes will recover as lockdown measures are eased

Surgical intervention for hydrocephalus in infancy; etiology, age and treatment data in a Dutch cohort

Contains fulltext : 217415.pdf (Publisher’s version ) (Open Access

A cross sectional study of the availability of paediatric emergency equipment in South African emergency units

CITATION: King, L. L., Cheema, B. & Van Hoving, D. J. 2020. A cross sectional study of the availability of paediatric emergency equipment in South African emergency units. African Journal of Emergency Medicine, 10(4):197-202, doi:10.1016/j.afjem.2020.06.008.The original publication is available at https://www.sciencedirect.com/journal/african-journal-of-emergency-medicineBackground: Despite children representing a significant proportion of Emergency Unit (EU) attendances glob- ally, it is concerning that many healthcare facilities are inadequately equipped to deliver paediatric resuscita- tion. The rapid availability of a full range of paediatric emergency equipment is critical for delivery of effective, best-practice resuscitation. This study aimed to describe the availability of essential, functional paediatric emergency resuscitation equipment on or close to the resuscitation trolley, in 24-hour EUs in Cape Town, South Africa. Methods: A cross sectional study was conducted over a six-month period in government funded hospital EUs, providing 24-hour emergency paediatric care within the Cape Town Metropole. A standardised data collection sheet of essential resuscitation equipment expected to be available in the resuscitation area, was used. Items were considered to be available if at least one piece of equipment was present. Functionality of available equipment was defined as: equipment that hadn't expired, whose original packaging was not outwardly damaged or compromised and all components were present and intact. Results: Overall, a mean of 43% (30/69) of equipment was available on the resuscitation trolley across all hospitals. The overall mean availability of equipment in the resuscitation area was 49% (34/69) across all hospitals. Mean availability of functional equipment was 42% (29/69) overall, 41% (28/69) at district-level hospitals, and 45% (31/69) at regional/tertiary hospitals. Conclusion: Essential resuscitation equipment for children is insufficiently available at district-level and higher hospitals in the Cape Town Metropole. This is a modifiable barrier to the provision of high-quality paediatric emergency care.https://www.sciencedirect.com/science/article/pii/S2211419X20300628?via%3DihubPublisher’s versio

PSMA, EpCAM, VEGF and GRPR as Imaging Targets in Locally Recurrent Prostate Cancer after Radiotherapy

In this retrospective pilot study, the expression of the prostate-specific membrane antigen (PSMA), the epithelial cell adhesion molecule (EpCAM), the vascular endothelial growth factor (VEGF) and the gastrin-releasing peptide receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or external beam radiotherapy (EBRT) was investigated, and their adequacy for targeted imaging was analyzed. Prostate cancer specimens were collected of 17 patients who underwent salvage prostatectomy because of locally recurrent prostate cancer after brachytherapy or EBRT. Immunohistochemistry was performed. A pathologist scored the immunoreactivity in prostate cancer and stroma. Staining for PSMA was seen in 100% (17/17), EpCAM in 82.3% (14/17), VEGF in 82.3% (14/17) and GRPR in 100% (17/17) of prostate cancer specimens. Staining for PSMA, EpCAM and VEGF was seen in 0% (0/17) and for GRPR in 100% (17/17) of the specimens’ stromal compartments. In 11.8% (2/17) of cases, the GRPR staining intensity of prostate cancer was higher than stroma, while in 88.2% (15/17), the staining was equal. Based on the absence of stromal staining, PSMA, EpCAM and VEGF show high tumor distinctiveness. Therefore, PSMA, EpCAM and VEGF can be used as targets for the bioimaging of recurrent prostate cancer after EBRT to exclude metastatic disease and/or to plan local salvage therapy

The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity

Open Access funded by Wellcome Trust: Under a Creative Commons license Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgments We would like to thank S. Hardison, P. Redelinghuys, J. Taylor, C. Wallace, A. Richmond, S. Hadebe, A. Plato, F. Abbass, L. Fick, N. Allie, R. Wilkinson, K. Wilkinson, S. Cooper, D. Lang, and V. Kumar for reagents and assistance, and the animal facility staff for the care of our animals. This work was supported by the MRC (UK) and Wellcome Trust (G.D.B.); MRC (South Africa) and Sydney Brenner Fellowship (M.J.M.); Vici (M.G.N.), Vidi (R.v.C.), and Veni grants (T.S.P.) from the Netherlands Organization for Scientific Research; the Royal Netherlands Academy of Arts and Sciences (T.H.M.O.); EC FP7 projects (NEWTBVAC, ADITEC; T.H.M.O.); Carnegie Corporation and CIDRI (J.C.H.); and the University of Aberdeen (B.K.).Peer reviewedPublisher PD

A comparison of trauma scoring systems for trauma-related injuries presenting to a district-level urban public hospital in Western Cape, South Africa

CITATION: Mukonkole, S. N. et al. 2020. A comparison of trauma scoring systems for trauma-related injuries presenting to a district-level urban public hospital in Western Cape, South Africa. South African Journal of Surgery, 58(1):9-14, doi:10.17159/2078-5151/2020/v58n1a3116.The original publication is available at: http://www.scielo.org.zaBACKGROUND: Trauma is a major public health issue and has an extensive burden on the health system in South Africa. Many trauma scoring systems have been developed to estimate trauma severity and predict mortality. The prediction of mortality between different trauma scoring systems have not been compared at district-level health facilities in South Africa. The objective was to compare four trauma scoring systems (injury severity score (ISS), revised trauma score (RTS), Kampala trauma score (KTS), trauma and injury severity score (TRISS)) in predicting mortality in trauma-related patients presenting to a district-level hospital in Cape Town METHODS: A retrospective analysis of all trauma patients managed in the resuscitation unit of Khayelitsha Hospital during a six-month period. Logistic regression was done, and empirical cut of points used to maximise sensitivity and specificity on receiver operating characteristic curves. The outcome was all-cause in-hospital mortality RESULTS: In total, 868 participants were analysed after 50 were excluded due to missing data. The mean (± SD) age was 28±11 years, 726 (83.6%) were males, and penetrating injuries (n = 492,56.6%) dominated. The mortality rate was 5.2% (n = 45). TRISS was the best mortality predictor (c-statistic 0.93, sensitivity 90%, specificity 87%). All scoring systems had overlapping confidence intervals CONCLUSION: TRISS, ISS, RTS and KTS performed equivocally in predicting mortality in trauma-related patients managed at a district-level facility. The appropriate scoring system should be the simplest one which can be practically implemented and will likely differ between facilitiesPublisher's versio

Synthesis and Evaluation of F-18-Enzalutamide, a New Radioligand for PET Imaging of Androgen Receptors:A Comparison with 16 beta-F-18-Fluoro-5 alpha-Dihydrotestosterone

16 beta-F-18-fluoro-5 alpha-dihydrotestosterone (F-18-FDHT) is a radiopharmaceutical that has been investigated as a diagnostic agent for the assessment of androgen receptor (AR) density in prostate cancer using PET. However, F-18-FDHT is rapidly metabolized in humans and excreted via the kidneys into the urine, potentially compromising the detection of tumor lesions close to the prostate. Enzalutamide is an AR signaling inhibitor currently used in different stages of prostate cancer. Enzalutamide and its primary metabolite N-desmethylenzalutamide have an AR affinity comparable to that of FDHT but are excreted mainly via the hepatic route. Radiolabeled enzalutamide could thus be a suitable candidate PET tracer for AR imaging. Here, we describe the radiolabeling of enzalutamide with F-18. Moreover, the in vitro and in vivo behavior of F-18-enzalutamide was evaluated and compared with the current standard, F-18-FDHT. Methods: F-18-enzalutamide was obtained by fluorination of the nitro precursor. In vitro cellular uptake studies with F-18-enzalutamide and F-18-FDHT were performed in LNCaP (AR-positive) and HEK293 (AR-negative) cells. Competition assays with both tracers were conducted on the LNCaP (AR-positive) cell line. In vivo PET imaging, ex vivo biodistribution, and metabolite studies with F-18-enzalutamide and F-18-FDHT were conducted on athymic nude male mice bearing an LNCaP xenograft in the shoulder. Results: F-18-enzalutamide was obtained in 1.4% +/- 0.9% radiochemical yield with an apparent molar activity of 6.2 +/- 10.3 GBq/mu mol. F-18-FDHT was obtained in 1.5% +/- 0.8% yield with a molar activity of more than 25 GBq/mu mol. Coincubation with an excess of 5 alpha-dihydrotestosterone or enzalutamide significantly reduced the cellular uptake of F-18-enzalutamide and F-18-FDHT to about 50% in AR-positive LNCaP cells but not in AR-negative HEK293 cells. PET and biodistribution studies on male mice bearing a LnCaP xenograft showed about 3 times higher tumor uptake for F-18-enzalutamide than for F-18-FDHT. Sixty minutes after tracer injection, 93% of F-18-enzalutamide in plasma was still intact, compared with only 3% of F-18-FDHT. Conclusion: Despite its lower apparent molar activity, F-18-enzalutamide shows higher tumor uptake and better metabolic stability than F-18-FDHT and thus seems to have more favorable properties for imaging of AR with PET. However, further evaluation in other oncologic animal models and patients is warranted to confirm these results

Clinical Applicability of Transient Elastography for Estimating Liver Stiffness in Patients with Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of non-alcoholic fatty liver disease, which can lead to liver fibrosis and ultimately to cirrhosis. Transient elastography (TE), by using the FibroScan, and is a non-invasive ultrasonography method to measure liver elasticity. TE has been related with the degree of liver fibrosis. Objective: To investigate the applicability of TE in daily clinical practice among T2DM patients. Method: In a non-academic teaching hospital, T2DM patients without a history of liver disease the degree of liver stiffness was measured using TE. Successful measurements were defined as 10 validated measurements per patient and an interquartile range (IQR) to median ratio of ≤30%. Results: In 90 of 126 patients (71%) valid measurements were be obtained. Among the patients with invalid measurements, 33 had < 10 valid measurements and 3 had a IQR to median ratio of <30%. The percentage of invalid measurements was 12% in patients with a BMI <30 kg/m2 and 39% in patients with a BMI ≥30 kg/m2. Among the 90 patients with valid liver stiffness measurements, the median liver stiffness was 6.7 [4.6-8.5] kPa with a IQR of measurements of 1.1 [0.6-1.8] kPa and IQR to median ratio of 17 (13-23)%. Conclusion: The success rate of TE measurements using the FibroScan in patients with T2DM was 71%, with a lower success rate in patients with a BMI ≥ 30 kg/m2. This diagnostic modality needs further investigation being introduced as a marker of fibrosis in daily diabetes practice

Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery

Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents