Does Engagement in HIV Care Affect Screening, Diagnosis, and Control of Noncommunicable Diseases in Sub-Saharan Africa? A Systematic Review and Meta-analysis.

Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

The stability of C-peptide and insulin in plasma and serum samples under different storage conditions.

OBJECTIVES: C-peptide and insulin are peptide hormones and their stability is affected by a number of pre-analytical factors. The study aimed to investigate the impact of sample type, storage temperature and time delays before centrifugation and analysis on the stability of C-peptide and insulin. METHODS: Ten healthy non-diabetic adults in fasting and non-fasting state were enrolled. 40 mL of blood was collected from each participant into SST and dipotassium EDTA tubes. Samples were centrifuged immediately or at timed intervals (8, 12, 48 and 72 h). After baseline measurements on the Roche Cobas e602 analyzer using electrochemiluminescence immunoassays, aliquots were stored at room temperature (RT), 2-8 and -20 °C for 4 h to 30 days. The percentage deviation (PD) from baseline was calculated and a change greater than desirable biological variation total error was considered clinically significant. RESULTS: C-peptide was more stable in separated serum than plasma (PD of -5 vs. -13 %) samples stored at 2-8 °C for 7 days and was most unstable at RT when centrifugation was delayed (PD -46 % in plasma and -74 % in serum after 48 h). Insulin was more stable in plasma than in serum under the different storage conditions with a minimum PD of -1% when stored at -20 °C for 30 days. When samples were kept unspun at RT for 72 h, PD was -23 and -80 % in plasma and serum, respectively. CONCLUSIONS: C-peptide was more stable in serum provided the sample was centrifuged immediately and stored in the fridge or freezer while insulin was found to be more stable in EDTA plasma.

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.

Gaps in the type 2 diabetes care cascade: a national perspective using South Africa's National Health Laboratory Service (NHLS) database.

BACKGROUND: Research out of South Africa estimates the total unmet need for care for those with type 2 diabetes mellitus (diabetes) at 80%. We evaluated the care cascade using South Africa's National Health Laboratory Service (NHLS) database and assessed if HIV infection impacts progression through its stages. METHODS: The cohort includes patients from government facilities with their first glycated hemoglobin A1c (HbA1c) or plasma glucose (fasting (FPG); random (RPG)) measured between January 2012 to March 2015 in the NHLS. Lab-diagnosed diabetes was defined as HbA1c ≥ 6.5%, FPG ≥ 7.0mmol/l, or RPG ≥ 11.1mmol/l. Cascade stages post diagnosis were retention-in-care and glycaemic control (defined as an HbA1c < 7.0% or FPG < 8.0mmol/l or RPG < 10.0mmol/l) over 24-months. We estimated gaps at each stage nationally and by people living with HIV (PLWH) and without (PLWOH). RESULTS: Of the 373,889 patients tested for diabetes, 43.2% had an HbA1c or blood glucose measure indicating a diabetes diagnosis. Amongst those with lab-diagnosed diabetes, 30.9% were retained-in-care (based on diabetes labs) and 8.7% reached glycaemic control by 24-months. Prevalence of lab-diagnosed diabetes in PLWH was 28.6% versus 47.3% in PLWOH. Among those with lab-diagnosed diabetes, 34.3% of PLWH were retained-in-care versus 30.3% PLWOH. Among people retained-in-care, 33.8% of PLWH reached glycaemic control over 24-months versus 28.6% of PLWOH. CONCLUSIONS: In our analysis of South Africa's NHLS database, we observed that 70% of patients diagnosed with diabetes did not maintain in consistent diabetes care, with fewer than 10% reaching glycemic control within 24 months. We noted a disparity in diabetes prevalence between PLWH and PLWOH, potentially linked to different screening methods. These differences underscore the intricacies in care but also emphasize how HIV care practices could guide better management of chronic diseases like diabetes. Our results underscore the imperative for specialized strategies to bolster diabetes care in South Africa.

SARS-CoV-2 Infection and the Kidneys: An Evolving Picture.

Since December 2019, a novel coronavirus known as Severe Acute Respiratory Virus 2 (SARS-CoV-2) has caused an outbreak of a respiratory illness worldwide. Even though SARS-CoV-2 primarily affects the respiratory system, other organs such as the heart and kidneys are implicated. The pathophysiology of Acute Kidney Injury (AKI) in coronavirus 2019 (COVID-19) patients is not clearly defined. Direct kidney injury results from virus entry through angiotensin-converting enzyme-2 (ACE2) receptors which are highly expressed by the podocytes and proximal convoluted tubules, as suggested by "viral-like" particles on electron microscopy. However, the link between the presence of viral particles in kidney tissue and kidney injury has not been fully explained. Furthermore, it is also hypothesized that collapsing focal segmental glomerulosclerosis (FSGS), myoglobin toxicity, sepsis-linked, and glomeruli fibrin thrombi is part of the mechanism for AKI. Reported cases link FSGS and high-risk apolipoprotein 1 (APOL1) alleles in patients of African ancestry. Typically, these patients present with AKI and nephrotic-range proteinuria. The rate of AKI in hospitalized patients is high and associated with a higher mortality rate in older patients with comorbidities. Even higher mortality is now being reported in patients with chronic kidney disease and kidney transplant recipients due to immune system dysfunction. Herein, we review the current literature on kidney disease and pathogenesis in COVID-19 patients.

Proteomic Analysis Identifies Dysregulated Proteins in Albuminuria: A South African Pilot Study.

Albuminuria may precede decreases in the glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. This case-controlled study compared the urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) < 3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC (Evosep Biosystems, Odense, Denmark) coupled to a Sciex 5600 Triple-TOF (Sciex, Framingham, MA, USA) in data-independent acquisition mode. The data were searched on SpectronautTM 15. Differentially abundant proteins (DAPs) were filtered to include those with a ≥2.25-fold change and a false discovery rate ≤ 1%. Receiver-operating characteristic curves were used to assess the discriminating abilities of proteins of interest. Pathway analysis was performed using Enrichr software. As expected, the albuminuric group had higher uACR (7.9 vs. 0.55 mg/mmol, p < 0.001). The median eGFR (mL/min/1.73 m2) showed no difference between the groups (111 vs. 114, p = 0.707). We identified 80 DAPs in the albuminuria group compared to the normoalbuminuria group, of which 59 proteins were increased while 21 proteins were decreased in abundance. We found 12 urinary proteins with an AUC > 0.8 and a p < 0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC ˃ 0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis found that the DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with a well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease.

Corrigendum: The application of sigma metrics in the laboratory to assess quality control processes in South Africa.

[This corrects the article DOI: 10.4102/ajlm.v11i1.1344.].

Does engagement in HIV care affect screening, diagnosis, and control of noncommunicable diseases in sub-Saharan Africa? A systematic review and meta-analysis.

Objective: Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under-resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and/or control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV (PLWH) in sub-Saharan Africa (SSA). Design: Systematic review and meta-analysis. Methods: We searched 10 electronic literature databases for studies published between 01 January 2011 and 31 December 2022 using a comprehensive search strategy. We sought studies reporting on screening, diagnosis, treatment, and/or control of NCDs of interest by ART use among non-pregnant adults with HIV ≥16 years of age in SSA. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. Results: Twenty-six studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART, were included. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR: 1.07; 95% CI: 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR: 2.10, 95% CI: 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Conclusion: Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.

A Macro-TSH: A Clinical Diagnostic Dilemma.

Isolated increase in thyrotropin stimulating hormone (TSH) in a clinically euthyroid patient may be caused by the formation of a macromolecule between TSH and autoantibodies causing discordant thyroid function test results. Despite the effort to eliminate interferences in immunoassays, these assays are still vulnerable to different interferences. Immunoassay interferences may cause erroneous results and lead to misdiagnosis which may subject a patient to unnecessary investigations and treatment. Immunoassays are affected by multiple substances; these may be endogenous or exogenous such as heterophile antibodies, autoantibodies, macromolecules, and human anti-mouse antibodies. This case reports a 47-year-old African woman who presented with a persistent elevated TSH with thyroid hormones within normal reference limits. She was found to have a macro-TSH which was associated with IgA paraprotein.

Comparison of measured LDL cholesterol with calculated LDL-cholesterol using the Friedewald and Martin-Hopkins formulae in diabetic adults at Charlotte Maxeke Johannesburg Academic Hospital/NHLS Laboratory.

BACKGROUND: The National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) and the European Society of Cardiology recommend using low-density lipoprotein cholesterol (LDL-C) as a treatment target for cholesterol lowering therapy. The Friedewald formula underestimates LDL-C in non-fasted and hypertriglyceridemia patients. This study aimed to compare measured LDL-C to calculated LDL-C in diabetic patients using the Friedewald and Martin-Hopkins formulae. METHODS: The data of 1 247 adult diabetes patients were retrospectively evaluated, and included triglycerides (TG), LDL-C, total cholesterol, and high-density lipoprotein cholesterol that were measured on the Roche Cobas® c702. Passing-Bablok regression analysis was used to determine the degree of agreement between measured LDL-C and calculated LDL-C using both formulae. The Bland-Altman plots were used to assess the bias at medical decision limits based on the 2021 European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention in clinical practice. RESULTS: Both formulae showed a good linear relationship against measured LDL-C. However, the Martin-Hopkins formula outperformed the Friedewald formula at LDL-C treatment target <1.4mmol/L. The Friedewald formula and the Martin-Hopkins formula had 14.9% and 10.9% mean positive bias, respectively. At TG-C ≥1.7 mmol/L, the Martin-Hopkins formula had a lower mean positive bias of 4.2% (95% CI 3.0-5.5) compared to the Friedewald formula, which had a mean positive bias of 21.8% (95% CI 19.9-23), which was higher than the NCEP ATP III recommended total allowable limit of 12%. CONCLUSION: The Martin-Hopkins formula performed better than the Friedewald formula at LDL-C of 1.4 mmol/L and showed the least positive bias in patients with hypertriglyceridemia.

The application of sigma metrics in the laboratory to assess quality control processes in South Africa.

Background: Laboratories use quality control processes to monitor and evaluate analytical performance in terms of precision and bias. Sigma metrics provide an objective assessment of laboratory quality using the total allowable error as an additional parameter. Objective: This study aimed to determine the sigma metrics of analytes when using different total allowable error guidelines. Methods: A retrospective analysis was performed on 19 general chemistry analytes at Charlotte Maxeke Johannesburg Academic Hospital in South Africa between January 2017 and December 2017. Sigma metrics were calculated on two identical analysers, using internal quality control data and total allowable error guidelines from the Ricos biological variation database and three alternative sources (the Royal College of Pathologists of Australasia, the Clinical Laboratory Improvements Amendment, and the European Federation of Clinical Chemistry and Laboratory Medicine). Results: The sigma performance was similar on both analysers but varied based on the guideline used, with the Clinical Laboratory Improvements Amendment guidelines resulting in the best sigma metrics (53% of analytes on one analyser and 46% on the other had acceptable sigma metrics) and the Royal College of Pathologists of Australia guidelines being the most stringent (21% and 23%). Sodium and chloride performed poorly across all guidelines (sigma < 3). There were also month-to-month variations that may result in acceptable sigma despite poor performance during certain months. Conclusion: The sigma varies greatly depending on the total allowable error, but could be a valuable tool to save time and decrease costs in high-volume laboratories. Sigma metrics calculations need to be standardised.

Comparative study of chemical pathology sample collection tubes at the largest hospital in South Africa.

BACKGROUND: BarricorTM Lithium heparin plasma tubes are new blood tubes that have been introduced to overcome the effects of gel in serum separator tubes (SST) and the shortcomings of standard Lithium heparin plasma. We aimed to evaluate BarricorTM tubes as an alternative to serum separator tubes and compare the stability between the tubes. METHODS: Forty-four paired samples were collected using both BarricorTM and SST. We compared five analytes at baseline (<6 h) and after every 24 h using the PassingBablok and Bland-Altman plots. Aspartate aminotransferase (AST), potassium (K), phosphate (PO4) , lactate dehydrogenase (LDH), and creatinine were analysed in both tubes. We calculated the percentage difference for each analyte between the baseline and time intervals to assess analyte stability. The percentage difference was compared to the desirable specification for bias and reference change value (RCV). RESULTS: All analytes were comparable at baseline. Statistical differences (p<0.001) became evident after 24 h. PO4, K, and creatinine had a mean difference that exceeded the desirable specification for bias (-9.59%, - 9.35%, and -4.59%, respectively). Potassium was stable up to 24 h in both tubes. LDH showed better stability in SST (144 h vs 96 h). PO4 concentrations were more stable in both tubes with the SST (96 h vs 72 h). Creatinine and AST had the longest stability in both tubes compared to other analytes (144 h). CONCLUSIONS: Data demonstrated variability and similarities in analyte concentrations and stability, respectively, in both tubes.

The effect of HIV infection on glycaemia and renal function in type 2 diabetic patients.

BACKGROUND: Infection with, and treatment of HIV is associated with effects on glycaemia and renal function. The purpose of this study was therefore to compare glycaemic control and albuminuria in HIV-positive and HIV-negative type 2 diabetic patients. MATERIALS AND METHODS: Diabetic patients with and without HIV infection were recruited from a diabetic clinic at Chris Hani Baragwanath Hospital in Soweto, South Africa. Data was collected on weight, height, HbA1c, fasting glucose, urine albumin:creatinine ratio, HIV status, CD4 counts, viral load and concomitant therapies. Multivariable regression analysis was used to isolate the determinants of fasting glucose and HbA1c levels and risk factors for albuminuria. RESULTS: Data were collected from 106 HIV-positive and 214 HIV-negative diabetics. All HIV infected subjects were receiving anti-retroviral therapy. The determinants of fasting glucose levels (log) were HIV infection (ß = 0.04, p = 0.01) and use of anti-hypertensive agents (ß = 0.07, p = 0.0006), whilst for HbA1c levels (log) they were HIV infection (ß = -0.03, p = 0.03), BMI (ß = 0.004, p = 0.0005), statin use (ß = 0.04, p = 0.002) and glucose levels (ß = 0.01, p<0.0005). In HIV-positive subjects, CD4 counts were negatively associated with glucose levels (ß = -0.0002, p = 0.03). The risk factors for albuminuria were (odds ratio [95% CIs]) dyslipidaemia (1.94 [1.09, 3.44], p = 0.02) and HbA1c levels (1.24 [1.12, 1.38], p<0.0001). DISCUSSION: These data suggest that glycaemic control is worse in type 2 diabetic subjects with HIV infection and that HbA1c underestimates glycaemia in these patients. Albuminuria was not associated with HIV-positivity. The negative relationship of CD4 counts with glucose levels may reflect viral removal and easing of the associated inflammatory response. It is possible that the association of statin and anti-hypertensive therapies with high HbA1c and glucose levels, respectively, is due to such therapies being given largely to subjects with poor glycaemic control.