Tricyclic antidepressant overdose necessitating ICU admission

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1 000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortalityof TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose

The impact of HIV infection on the presentation of lung cancer in South Africa

Background. Despite the very high background prevalence of HIV and smoking-related diseases in sub-Saharan Africa, very little is known about the presentation of lung cancer in HIV-infected individuals.Methods. We prospectively compared HIV-positive (n=44) and HIV-negative lung cancer patients (n=425) with regard to demographics, cell type, performance status and tumour node metastasis staging at initial presentation.Results. HIV-positive patients were found to be younger than HIV-negative (mean 54.1 (standard deviation 8.4) years v. 60.5 (10) years, p<0.01), more likely to have squamous cell carcinoma (43.2% v. 30.1%, p=0.07) and significantly more likely to have a poor Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 (47.7% v. 29.4%, p=0.02). In the case of non-small cell-lung cancer, they were also significantly less likely to have early stage lung cancer (0% v. 10.3%, p=0.02)  compared with HIV-negative patients.Conclusions. HIV-positive lung cancer patients were younger, significantly more likely to have a poor performance status at presentation and significantly less likely to have early stage lung cancer when compared with HIV-negative patients

The impact of an electronic clinical decision support for pulmonary embolism imaging on the efficiency of computed tomography pulmonary angiography utilisation in a resource-limited setting

Background. Pulmonary embolism (PE) is associated with high morbidity and mortality. Effective intervention requires prompt diagnosis. Computed tomography pulmonary angiography (CTPA) is sensitive and specific for PE and is the investigation of choice. Inappropriate CTPA utilisation results in unnecessary high radiation exposure and is costly. State-of-the-art electronic radiology workflow can provide clinical decision support (CDS) for specialised imaging requests, but there has been limited work on the clinical impact of CDS in PE, particularly in resource-constrained environments.Objective. To determine the impact of an electronic CDS for PE on the efficiency of CTPA utilisation in a resource-limited setting.Methods. In preparation, a PE diagnostic algorithm was distributed to hospital clinicians, explaining the combined role of the validated modified Wells score and the quantitative D-dimer test in defining the pre-test probability of PE. Thereafter, an automated, electronic CDS was introduced for all CTPA requests. Total CTPA referrals and the proportion positive for PE were assessed for three study phases: (i) prediagnostic algorithm; (ii) post-algorithm, pre-CDS; and (iii) post-CDS.Results. The proportion of CTPAs positive for PE after CDS implementation was almost double that prior to introduction of the diagnostic algorithm (phase 1 v. 3, 17.4% v. 30.7%; p=0.036), with a correspondingly significant decrease in the proportion of non-positive CTPAs (phases 1 v. 3, 82.6% v. 69.3%; p=0.015) During phases 2 and 3, no CTPAs were requested for patients with a modified Wells score of ≤4 and a documented negative D-dimer, indicating adherence to the algorithm.Conclusion. Implementing an electronic CDS for PE significantly increased the efficiency of CTPA utilisation and significantly decreased the proportion of inappropriate scans

Validation of a severity-of-illness score in patients with tuberculosis requiring intensive care unit admission

Background. There is a paucity of data on the determinants of mortality due to tuberculosis (TB) in the intensive care unit (ICU).Objective. To develop a simple severity-of-illness score for use in patients with TB admitted to an ICU.Methods. A scoring system was generated by retrospectively identifying the four most significant and clinically unrelated predictors of mortality from an existing prospectively collected dataset (January 2012 - May 2013), and combining these with known predictors of poor outcome.Results. Of 83 patients admitted with TB, 38 (45.8%) died in the ICU. The four parameters identified from the retrospective analysis were: (i) HIV co-infection with a CD4 cell count <200/ƒÊL; (ii) a raised creatinine level: (iii) a chest radiograph showing diffuse parenchymal infiltrates/miliary pattern; and (iv) absence of TB treatment on admission. These were combined with septic shock and a low arterial partial pressure of oxygen/fractional inspired oxygen (P:F) ratio to generate a six-point severity-of-illness score (one point for each parameter). The scores for survivors were significantly lower than those for  non-survivors (mean (standard deviation) 2.27 (1.47) v. 3.58 (1.08); p<0.01). A score of .2 was associated with significantly higher mortality than a score of <2 (7.1% v. 46.4%; odds ratio (OR) 15.03; 95% confidence interval (CI) 1.86 - 121.32; p<0.01), whereas a score of .3 was associated with a significantly higher mortality than a score of <3 (64.6% v. 20.0%; OR 7.29; 95% CI 2.64 - 20.18; p<0.01).Conclusion. The proposed scoring system identified patients at increased risk of dying from TB in the ICU. Further prospective studies are indicated to validate its use

The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area

Background. Integrated positron emission tomography/computed tomography (PET-CT) is a  well-validated modality for assessing pulmonary mass lesions and specifically for estimating risk of malignancy. Tuberculosis (TB) is known to cause false-positive PET-CT findings.Objective. To investigate the utility of PET-CT in the evaluation of pulmonary mass lesions and nodules in a high TB prevalence setting.Methods. All patients referred for the evaluation of a solitary pulmonary nodule or mass and who  underwent PET-CT scanning over a 3-year period were included. The PET-CT findings, including maximum  standardised uptake value (SUVmax), were compared with the gold standard (tissue or microbiological diagnosis). The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for malignant disease were calculated according to the SUVmax cut-off of 2.5 and a proposed cut-off  obtained from a receiver operating characteristic (ROC) curve.Results. Forty-nine patients (mean (standard deviation) age 60.1 (10.2) years; 29 males) were included, of whom 30 had malignancy. Using an SUVmax cut-off of 2.5, PET-CT had a sensitivity, specificity,  positive and negative predictive value and diagnostic accuracy for malignancy of 93.3%, 36.8%, 70.0%, 77.8% and 71.4%, respectively. After a ROC curve analysis, a suggested SUVmax cut-off of 5.0 improved the specificity to 78.9% and the diagnostic accuracy to 86.7%, with a small reduction in sensitivity to 90.0%.Conclusions. The diagnostic accuracy of PET-CT in the evaluation of pulmonary mass lesions using the conventional SUVmax cut-off of 2.5 was reduced in a TB-endemic area. An SUVmax cut-off of 5.0 has a higher specificity and diagnostic accuracy for malignancy, with a comparable sensitivity

Predicting COVID-19 outcomes from clinical and laboratory parameters in an intensive care facility during the second wave of the pandemic in South Africa

Background: The second wave of coronavirus disease 2019 (COVID-19) in South Africa was caused by the Beta variant of severe acute respiratory syndrome coronavirurus-2. This study aimed to explore clinical and biochemical parameters that could predict outcome in patients with COVID-19. Methods: A prospective study was conducted between 5 November 2020 and 30 April 2021 among patients with confirmed COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital. The Cox proportional hazards model in Stata 16 was used to assess risk factors associated with survival or death. Factors with P<0.05 were considered significant. Results: Patients who died were found to have significantly lower median pH (P<0.001), higher median arterial partial pressure of carbon dioxide (P<0.001), higher D-dimer levels (P=0.001), higher troponin T levels (P=0.001), higher N-terminal-prohormone B-type natriuretic peptide levels (P=0.007) and higher C-reactive protein levels (P=0.010) compared with patients who survived. Increased standard bicarbonate (HCO3std) was associated with lower risk of death (hazard ratio 0.96, 95% confidence interval 0.93–0.99). Conclusions: The mortality of patients with COVID-19 admitted to the ICU was associated with elevated D-dimer and a low HCO3std level. Large studies are warranted to increase the identification of patients at risk of poor prognosis, and to improve the clinical approach

The prevalence of pulmonary hypertension after successful tuberculosis treatment in a community sample of adult patients

There are an estimated 155 million survivors of tuberculosis (TB). Clinical experience suggests that post-pulmonary tuberculosis lung disease (PTLD) is an important cause of group 3 pulmonary hypertension (PH). However, TB is not listed as a cause of PH in most guidelines. A cross-sectional, community-based study was conducted in non-health care seeking adults who had successfully completed TB treatment. Subjects underwent questionnaires, spirometry, a six-minute walk distance test (6MWD) and transthoracic echocardiography (TTE). Screen probable PH was defined on TTE as an estimated pulmonary artery peak systolic pressure (PASP) of ≥40mmHg. One hundred adults (71 males) were enrolled, with a mean age of 42 years (SD 13.8 years) and a median of one TB episode (IQR: 1 -2). Co-morbidities included hypertension (21%), diabetes (16%), HIV (10%) and asthma/COPD (5%). Only 25% had no residual symptoms after TB. Probable PH was found in 9%, while 7% had borderline raised PASP values (PASP 35-40mmHg). An association was found between PH and the number of previous TB episodes, with each additional episode of TB increasing the odds of PH-post-TB 2.13-fold (CI 1.17-3.88; P=0.013). All of those found to have PH were smokers or ex-smokers yielding an unadjusted odds ratio for PH-post-TB of 3.67 (95%CI 0.77-17.46). There was no statistical difference in spirometry or 6MWD, between those with and without PH. Neither symptoms nor co-morbidities demonstrated significant association with PH. PH after TB was a common finding in this community-based population. Further research is needed to confirm and determine the significance of these findings

Latent class analysis: an innovative approach for identification of clinical and laboratory markers of disease severity among COVID-19 patients admitted to the intensive care unit

Objective: The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town. Methods and results: A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L; p < 0.001), end-organ dysfunction (creatinine, median value 79 µmol/L vs 69.5 µmol/L; p < 0.003), under-perfusion markers (lactate, median value 1.60 mmol/L vs 1.20 mmol/L; p < 0.001), abnormal cardiac function markers (median N‐terminal pro‐brain natriuretic peptide (NT-proBNP) 314 pg/ml vs 63.5 pg/ml; p < 0.001 and median high‐sensitivity cardiac troponin (Hs-TropT) 39 ng/L vs 12 ng/L; p < 0.001), and acute inflammatory syndrome (median neutrophil-to-lymphocyte ratio 15.08 vs 8.68; p < 0.001 and median monocyte value 0.68 × 109/L vs 0.45 × 109/L; p < 0.001). Conclusion: The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU

Comparison of patients with severe COVID-19 admitted to an intensive care unit in South Africa during the first and second wave of the COVID-19 pandemic

BACKGROUND: The second wave of coronavirus disease 2019 (COVID‑19), dominated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant, has been reported to be associated with increased severity in South Africa (SA). OBJECTIVES: To describe and compare clinical characteristics, management and outcomes of COVID‑19 patients admitted to an intensive care unit (ICU) in SA during the first and second waves. METHODS: In a prospective, single-centre, descriptive study, we compared all patients with severe COVID‑19 admitted to ICU during the first and second waves. The primary outcomes assessed were ICU mortality and ICU length of stay (LOS). RESULTS: In 490 patients with comparable ages and comorbidities, no difference in mortality was demonstrated during the second compared with the first wave (65.9% v. 62.5%, p=0.57). ICU LOS was longer in the second wave (10 v. 6 days, p<0.001). More female admissions (67.1% v. 44.6%, p<0.001) and a greater proportion of patients were managed with invasive mechanical ventilation than with non-invasive respiratory support (39.0% v. 14%, p<0.001) in the second wave. CONCLUSIONS: While clinical characteristics were comparable between the two waves, a higher proportion of patients was invasively ventilated and ICU stay was longer in the second. ICU mortality was unchanged

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature