The burden and outcomes of firearm injuries at two district-level emergency centres in Cape Town, South Africa: A descriptive analysis.

BACKGROUND: In South Africa (SA), injuries are the second leading cause of years of healthy life lost, and interpersonal violence dominates the SA injury profile. Half of all injury-related deaths in SA are intentional, and firearms contribute to a quarter of these deaths. Injury surveillance systems are essential to develop, implement and monitor strategies that reduce preventable trauma. OBJECTIVES: To describe the burden of patients with firearm injuries and their outcomes at district-level emergency centres in the Western Cape. METHODS: This study was a retrospective analysis of a prospectively collected database. All patients who presented to two district-level emergency centres with a firearm injury over a 12-month period (1 January 2019 - 31 December 2019) were eligible for inclusion. RESULTS: Firearm injuries represented 5.7% of the trauma burden at the two district emergency centres. Of the 776 patients with firearm injuries who were included, the median age was 27 years, and 91% were male. A total of 520 (67%) patients self-presented, and there were 18 (2.3%) deaths in the emergency centre and a further 23 (3%) as inpatients. Of the total where wound location was determined (n=595), 30.4% sustained more than one firearm injury, and 112 out of the 167 admitted to Mitchells Plain Hospital required at least one visit to theatre. This accounted for 413 theatre hours and 1 376 inpatient bed days at Mitchells Plain Hospital. A significant proportion of patients (n=219, 29%) were transferred from the emergency centres to a tertiary service for further care. CONCLUSION: Firearm injuries represent a substantial proportion of the trauma burden at district emergency centres in the Western Cape Province. Managing patients with firearm injuries is resource intensive, as evident by their high acuity, the need for operative care, the long length of stay, the high burden on emergency medical services with interfacility transfers and the high demand for tertiary care. Data from this study aid our understanding of the prevalence and burden of firearm injuries at district level emergency centres, and multisectoral action, supported by evidence-based primary and secondary preventive strategies, is required to reduce the burden of firearm injuries, and mitigate their effects.

Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort.

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Ketamine as adjunctive or monotherapy for post-intubation sedation in patients with trauma on mechanical ventilation: A rapid review.

Background: The effectiveness of ketamine as adjunctive or monotherapy for post-intubation sedation in adults with trauma on mechanical ventilation is unclear. Methods: A rapid review of systematic reviews of randomized controlled trials, then randomized controlled trials or observational studies was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on June 1, 2022. We used a prespecified protocol following Cochrane rapid review methods. Results: We identified eight systematic reviews of randomized controlled trials and observational studies. Among the included reviews, only the most relevant, up to date, highest quality-assessed reviews and reviews that reported on critical outcomes were considered. Adjunctive ketamine showed a morphine sparing effect (MD -13.19 µmg kg-1 h-1, 95 % CI -22.10 to -4.28, moderate certainty of evidence, 6 RCTs), but no to little effect on midazolam sparing effect (MD 0.75 µmg kg-1 h-1, 95 % CI -1.11 to 2.61, low certainty of evidence, 6 RCTs) or duration of mechanical ventilation in days (MD -0.17 days, 95 % CI -3.03 to 2.69, moderate certainty of evidence, 3 RCTs).Adjunctive ketamine therapy may reduce mortality (OR 0.88, 95 % CI 0.54 to 1.43, P = 0.60, very low certainty of evidence, 5 RCTs, n = 3076 patients) resulting in 30 fewer deaths per 1000, ranging from 132 fewer to 87 more, but the evidence is very uncertain. Ketamine results in little to no difference in length of ICU stay (MD 0.04 days, 95 % CI -0.12 to 0.20, high certainty of evidence, 5 RCTs n = 390 patients) or length of hospital stay (MD -0.53 days, 95 % CI -1.36 to 0.30, high certainty of evidence, 5 RCTs, n = 277 patients).Monotherapy may have a positive effect on respiratory and haemodynamic outcomes, however the evidence is very uncertain. Conclusion: Adjunctive ketamine for post-intubation analgosedation results in a moderate meaningful net benefit but there is uncertainty for benefit and harms as monotherapy.

Acute angioedema in Cape Town emergency centres and a suggested algorithm to simplify and improve management.

BACKGROUND: Angioedema is the most common acute allergic presentation to emergency centres (EC), with hospitalisation rates increasing in high-income countries. Angioedema can complicate with life-threatening laryngeal obstruction. There are no local data; therefore, we aimed to characterise acute angioedema cases presenting to ECs and develop a simple management algorithm. OBJECTIVE: To characterise the clinical presentation, management and outcomes of acute angioedema cases presenting to ECs. Based on these findings, we developed a management algorithm for acute angioedema to improve the care of acute angioedema in South Africa (SA). METHODS: We conducted a retrospective folder review of all patients admitted to Groote Schuur Hospital (tertiary) and Mitchells Plain District Hospital (secondary) ECs from 1  June 2018 to 31  June 2020. Using ICD-10 coding, folders of adults ≥18 years with possible angioedema presenting to the ECs were screened. An allergist extracted demographics, medical history, management and outcome data for each angioedema event. RESULTS: A total of 142 acute angioedema episodes were included, with a median (interquartile range) age of 42 (28 - 58) years, and 62% of patients were female. The majority (124/142, 87%) of acute angioedema EC presentations involved swelling above the shoulders, with airway involvement in 20 (14%) patients, with two patients requiring intubation. Nineteen (13%) patients required admission, with five (26%) admitted to high care/intensive care. Drug-induced angioedema was the most common cause, with 64/142 (45%) linked to a known offending drug, 42/64 (65.6%) being angiotensin-converting enzyme inhibitor (ACE-I). Critical information to guide angioedema management, including past personal/family allergy history, and duration of angioedema prior to EC visit, was not recorded in 64.7% and 37.8% of EC records, respectively. Unnecessary treatment with corticosteroids or antihistamines occurred in 19/53 (36%) and 16/53 (30%) cases with bradykinin-mediated angioedema ACE-I angioedema and hereditary angioedema). Overall, only 36/142 (25%) of angioedema patients were connected to allergy care. CONCLUSION: Angioedema is the most common allergy presentation to two ECs in Cape Town, SA. Bradykinin-mediated angioedema secondary to ACE-I therapy is the single most common offender, and was not appropriately managed in more than a third of cases. Based on these findings, we have developed a management algorithm that easily stratifies patients into bradykinin or mast cell-mediated angioedema with a step-by-step management approach that is applicable to the SA context. Ongoing awareness and education on allergy emergencies are required to ensure accurate diagnosis of less common causes of angioedema (particularly bradykinin-mediated angioedema) and linkage to allergy specialist care.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

BACKGROUND: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. OBJECTIVE: To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. METHODS: A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. RESULTS: We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. CONCLUSION: Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: The RAS/RAF/MEK/ERK (MAPK) pathway plays a role in ovarian carcinogenesis. Low-grade serous ovarian carcinoma (LGSOC) frequently harbors activating MAPK mutations. MAPK inhibitors have been used in small subsets of ovarian carcinoma (OC) patients to control tumor growth. Therefore, we performed a meta-analysis to evaluate the effectiveness of MAPK inhibitors in OC patients. We aimed to determine the clinical benefit rate (CBR), the subgroup of MAPK inhibitors with the best CBR and overall response rate (ORR), and the most common adverse events. METHODS: We conducted a search in PubMed, Embase via Ovid, the Cochrane library and clinicaltrials.gov on studies evaluating the efficacy of single MAPK pathway inhibition with MAPK pathway inhibitors in OC patients. Our primary outcome included the CBR, defined by the proportion of patients with stable disease (SD), complete (CR) and partial response (PR). Secondary outcomes included the ORR (including PR and CR) and grade 3 and 4 adverse events. Meta-analysis was performed using a random-effects model. RESULTS: We included nine studies with a total of 319 OC patients, for which we determined a pooled CBR of 63% (95%-CI 39-84%, I2 = 92%). Combined treatment with Raf- and MEK inhibitors in in BRAFv600 mutated LGSOC (n = 6) had the greatest efficacy with a CBR of 100% and ORR of 83%. MEK inhibitors had the best efficacy as a single agent. Subgroup analysis by tumor histology demonstrated a significantly higher CBR and ORR in patients with LGSOC, with a pooled CBR and ORR of 87% (95%-CI 81-92%, I2 = 0%) and 27% (95%-CI 10-48%, I2 = 77%) respectively. Adverse events of grade 3 or higher were reported frequently: 123 in 167 patients. CONCLUSIONS: MEK inhibitors are the most promising single agents in (LGS)OC. However, dual MAPK pathway inhibition should be considered in patients with a BRAFv600 mutation, or non-mutated OC with depleted treatment options due indications of higher efficacy and tolerable toxicity profiles.

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.

[Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: review of the literature]. / Percutane vertebroplastiek bij de behandeling van osteoporotische wervelinzakkingsfracturen; literatuuronderzoek.

OBJECTIVE: To determine the effectiveness and safety of percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures as published in the scientific literature. DESIGN: Literature review. METHOD: Medline and the Cochrane library were searched with the terms 'percutaneous vertebroplasty', 'vertebral compression fractures', 'osteoporotic' and 'osteoporosis'. Criteria for inclusion were: (a) the studies had to have been published in the period January 1985-August 2002, (b) the study population had to include at least 10 patients, (c) the patients had to have been treated with percutaneous vertebroplasty, and (d) the diagnosis had to have been 'osteoporotic vertebral compression fracture'. RESULTS: Twelve studies met the inclusion criteria. Pain relief was seen in 60%-100% of the patients within the first 24 hours and this result improved to 78-100% in the long term (maximum 4 years). The complications immediately after the procedure were related to cement leakages and were mostly of no clinical consequence. Serious complications such as pulmonary embolism were rare. In the long term, percutaneous vertebroplasty was associated with an increased risk of fractures in the adjacent vertebrae. CONCLUSION: Percutaneous vertebroplasty seems to be effective and safe in the treatment of osteoporotic vertebral compression fractures. A prospective randomised intervention study has, however, not yet been performed. For the time being, percutaneous vertebroplasty should be reserved for carefully selected patients in whom conservative therapy has not produced results.