Hemoperfusion for Clinically Suspected Organophosphate and Carbamate Poisoning in Critically Ill Patients: A Randomized Trial.

INTRODUCTION: Organophosphate poisoning occurs frequently, and despite treatment, increased severity and intensive care unit (ICU) admissions have been observed. We hypothesized that early hemoperfusion/hemadsorption (HA) therapy would change the clinical course of the disease. METHODS: We performed a prospective, open, randomized controlled study at an academic ICU. Adult patients referred for an acute cholinergic toxidrome were screened. Patients meeting inclusion and exclusion criteria were randomized to standard of care (SoC) or HA therapy plus SoC, which included 2 6-h cycles of HA 12 h apart beginning within the first 24 h of ICU admission. The primary outcome was a comparison of ICU length of stay (LOS). RESULTS: There were no significant baseline differences between the groups. The median ICU LOS was 6.5 days (IQR 4.5-10) in the HA group compared to 8 days (IQR 3.5-17) for the control group, p = 0.58. Among patients with an excess ICU LOS ≥7 days, the median ICU LOS was significantly shorter for the HA group, 10 days (IQR 8-12) compared to 17 days (IQR 14-22) for the control group, p = 0.001, resulting in a cost saving of EUR 7308 per patient. Duration (8 days vs. 13.5 days) and cumulative dosage (316 mg vs. 887 mg) of atropine among patients with excess ICU LOS were significantly lower in the HA group compared to the SoC group, respectively. A similar reduction in the duration of mechanical ventilation (HA = 6 days vs. SoC = 15 days, p = 0.001) was found. The combination of day 28 mortality and severe complications was lower in the HA group (10%, n = 2/20) compared to the SoC group (42%, 14/33) p = 0.01. CONCLUSION: HA therapy resulted in significant cost savings driven by a reduced LOS among patients with excess ICU LOS ≥7 days. This therapy was also associated with a significant reduction in the combination of day 28 mortality and severe complications including cardiac arrest, organ dysfunction, reintubation, and tracheostomy.

Using text mining techniques to extract prostate cancer predictive information (Gleason score) from semi-structured narrative laboratory reports in the Gauteng province, South Africa.

BACKGROUND: Prostate cancer (PCa) is the leading male neoplasm in South Africa with an age-standardised incidence rate of 68.0 per 100,000 population in 2018. The Gleason score (GS) is the strongest predictive factor for PCa treatment and is embedded within semi-structured prostate biopsy narrative reports. The manual extraction of the GS is labour-intensive. The objective of our study was to explore the use of text mining techniques to automate the extraction of the GS from irregularly reported text-intensive patient reports. METHODS: We used the associated Systematized Nomenclature of Medicine clinical terms morphology and topography codes to identify prostate biopsies with a PCa diagnosis for men aged > 30 years between 2006 and 2016 in the Gauteng Province, South Africa. We developed a text mining algorithm to extract the GS from 1000 biopsy reports with a PCa diagnosis from the National Health Laboratory Service database and validated the algorithm using 1000 biopsies from the private sector. The logical steps for the algorithm were data acquisition, pre-processing, feature extraction, feature value representation, feature selection, information extraction, classification, and discovered knowledge. We evaluated the algorithm using precision, recall and F-score. The GS was manually coded by two experts for both datasets. The top five GS were reported, with the remaining scores categorised as "Other" for both datasets. The percentage of biopsies with a high-risk GS (≥ 8) was also reported. RESULTS: The first output reported an F-score of 0.99 that improved to 1.00 after the algorithm was amended (the GS reported in clinical history was ignored). For the validation dataset, an F-score of 0.99 was reported. The most commonly reported GS were 5 + 4 = 9 (17.6%), 3 + 3 = 6 (17.5%), 4 + 3 = 7 (16.4%), 3 + 4 = 7 (14.7%) and 4 + 4 = 8 (14.2%). For the validation dataset, the most commonly reported GS were: (i) 3 + 3 = 6 (37.7%), (ii) 3 + 4 = 7 (19.4%), (iii) 4 + 3 = 7 (14.9%), (iv) 4 + 4 = 8 (10.0%) and (v) 4 + 5 = 9 (7.4%). A high-risk GS was reported for 31.8% compared to 17.4% for the validation dataset. CONCLUSIONS: We demonstrated reliable extraction of information about GS from narrative text-based patient reports using an in-house developed text mining algorithm. A secondary outcome was that late presentation could be assessed.

The Role of Inflammation in the Development of GDM and the Use of Markers of Inflammation in GDM Screening.

Gestational diabetes mellitus is a hyperglycaemic state first recognised in pregnancy. GDM affects both mother and child. Women with GDM and their new-borns are at risk of developing type 2 diabetes in the future. The screening and diagnostic criteria for GDM are inconsistent and thus novel biomarkers of GDM are required to strengthen the screening and diagnostic processes in GDM. Chronic low-grade inflammation is linked to the majority of the well-established risk factors of GDM such as old age, obesity and PCOS. This review provides an overview of the present knowledge on the pathology of GDM, the screening criteria applied, the role of inflammation in the development of GDM and the use of markers of inflammation namely cytokines, oxidative stress markers, lipids, amino acids and iron markers in screening and diagnosis of GDM.

Diabetic control and compliance using glycated haemoglobin (HbA1C) testing guidelines in public healthcare facilities of Gauteng province, South Africa.

OBJECTIVE: This study aimed at evaluating diabetic control and compliance with testing guidelines, across healthcare facilities of Gauteng Province, South Africa, as well as factors associated with time to achieve control. South Africa's estimated total unmet need for care for patients with type 2 diabetes mellitus is 80%. RESEARCH DESIGN, METHODS AND FINDINGS: The data of 511 781 patients were longitudinally evaluated. Results were reported by year, age category, race, sex, facility and test types. HbA1C of ≤7% was reported as normal, >7 - ≤9% as poor control and >9% as very poor control. The chi-squared test was used to assess the association between a first-ever HbA1C status and variables listed above. The Kaplan-Meier analysis was used to assess probability of attaining control among those who started with out-of-control HbA1C. The extended Cox regression model assessed the association between time to attaining HbA1C control from date of treatment initiation and several covariates. We reported hazard ratios, 95% confidence intervals and p-values. Data is reported for 511 781 patients with 705 597 laboratory results. Poorly controlled patients constituted 51.5%, with 29.6% classified as very poor control. Most poorly controlled patients had only one test over the entire study period. Amongst those who started with poor control status and had at least two follow-up measurements, the likelihood of achieving good control was higher in males (adjusted Hazard Ratio (aHR) = 1.16; 95% CI:1.12-1.20; p<0.001) and in those attending care at hospitals (aHR = 1.99; 95% CI:1.92-2.06; p<0.001). CONCLUSION: This study highlights poor adherence to guidelines for diabetes monitoring.

Mining laboratory data to describe prostate specific antigen testing and prostate cancer in Johannesburg, South Africa.

INTRODUCTION: guidelines issued by different organizations worldwide differ on the use of prostate specific antigen (PSA) in prostate cancer. However, no local data is available describing how PSA testing is offered by our healthcare facilities in the country. The objectives of this study were to describe PSA testing and subsequent prostate biopsy uptake in a South African urban population. METHODS: this was a descriptive retrospective study. Data of all PSA tests and prostate biopsies performed at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) laboratory for 2013 calendar year was extracted from the laboratory information system. RESULTS: a total of 20 365 PSA tests were performed on 17 481 men during the study period. The majority of men were Black African (79%). The mean age for Black Africans (55.5 years, SD 13.3) was significantly lower than other racial groups (62.9 years, SD 12.6, p < 0.0005). PSA level was lower in Black Africans compared to others. Prostate biopsy uptake across all age groups was lower in Black African men compared to others (2% versus 4%, p = 0.01). Of the 423 men who had a prostate biopsy, 50% had prostate cancer. More Black African men were diagnosed with prostate cancer on biopsy compared to men of other racial groups (54% versus 43%, p = 0.03). CONCLUSION: our study confirms that PSA testing is prevalent in healthcare facilities in South Africa. Black African men are tested for PSA levels but have low biopsy uptake and are more likely to be diagnosed with prostate cancer.

Diagnostic accuracy of plasma kynurenine/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis.

INTRODUCTION: The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB. METHOD: We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV. RESULTS: The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from -0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P<0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P<0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%. CONCLUSION: The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.

Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?

Progression from latency to active Tuberculosis (TB) disease is mediated by incompletely understood host immune factors. The definitive characteristic of progressive human immunodeficiency virus (HIV) disease is a severe loss in number and function of T lymphocytes. Among the many possible mediators of T lymphocyte loss and ineffective function is the activity of the immune-modulatory enzyme indoleamine 2,3-dioxygenase (IDO). IDO is the rate-limiting enzyme converting tryptophan to kynurenine. IDO activity was initially recognized to mediate tolerance at the foeto-maternal interface. Recently, IDO activity has also been noted to play a critical role in immune tolerance to pathogens. Studies of host immune and metabolic mediators have found IDO activity significantly elevated in HIV and TB disease. In this review, we explore the link between IDO-mediated tryptophan catabolism and the presence of active TB disease in HIV-infected patients. We draw attention to increased IDO activity as a key factor marking the progression from latent to active TB disease in HIV-infected patients.