Research Articles (Chemical Pathology)
Permanent URI for this collection
Browse
Recent Submissions
Now showing 1 - 5 of 48
- ItemPioneering BRCA1/2 Point-Of-Care Testing for Integration of Germline and Tumor Genetics in Breast Cancer Risk Management: A Vision for the Future of Translational Pharmacogenomics(Frontiers Media S.A, 2021-09) Mampunye, Lwando; Van der Merwe, Nerina C.; Grant, Kathleen A.; Peeters, Armand V.; Torrorey-Sawe, Rispah; French, David J.; Moremi, Kelebogile E.; Kidd, Martin; Van Eeden, Petrus C.; Pienaar, Fredrieka M.; Kotze, Maritha J.Research performed in South African (SA) breast, ovarian and prostate cancer patients resulted in the development of a rapid BRCA point-of-care (POC) assay designed as a time- and cost-effective alternative to laboratory-based technologies currently used for first-tier germline DNA testing. In this study the performance of the new assay was evaluated for use on a portable screening device (ParaDNA), with the long-term goal to enable rollout at POC as an inventive step to meet the World Health Organization’s sustainable development goals for Africa. DNA samples for germline testing were obtained retrospectively from 50 patients with early-stage hormone receptor-positive breast cancer referred for genomic tumor profiling (MammaPrint). Currently, SA patients with the luminal-type breast cancer are not routinely selected for BRCA1/2 testing as is the case for triple-negative disease. An initial evaluation involved the use of multiple control samples representing each of the pathogenic founder/recurrent variants included in the BRCA 1.0 POC Research Assay. Comparison with a validated laboratory-based first-tier real-time polymerase chain reaction (PCR) assay demonstrated 100% concordance. Clinical utility was evident in five patients with the founder BRCA2 c.7934delG variant, identified at the 10% (5/50) threshold considered cost-effective for BRCA1/2 testing. BRCA2 c.7934delG carrier status was associated with a significantly younger age (p=0.03) at diagnosis of breast cancer compared to non-carriers. In three of the BRCA2 c.7934delG carriers a high-risk MammaPrint 70-gene profile was noted, indicating a significantly increased risk for both secondary cancers and breast cancer recurrence. Initiating germline DNA testing at the POC for clinical interpretation early in the treatment planning process, will increase access to the most common pathogenic BRCA1/2 variants identified in SA and reduce loss to follow-up for timely gene-targeted risk reduction intervention. The ease of using cheek swabs/saliva in future for result generation within approximately one hour assay time, coupled with low cost and a high BRCA1/2 founder variant detection rate, will improve access to genomic medicine in Africa. Application of translational pharmacogenomics across ethnic groups, irrespective of age, family history, tumor subtype or recurrence risk profile, is imperative to sustainably implement preventative healthcare and improve clinical outcome in resource-constrained clinical settings.
- ItemAssessment of the association of plant- based diets with cardiovascular disease risk profile in Africa: a systematic review and meta-analysis protocol(BMJ Publishing, 2020-06) Lopes, Tatum; Zemlin, Annalise E.; Erasmus, Rajiv T.; Faber, Mieke; Kengne, Andre P.Introduction Cardiovascular disease (CVD) is currently the leading cause of death worldwide. In Africa where infectious diseases are still the leading cause of death, the contribution of non-communicable diseases led by CVDs has significantly increased in recent years. The rise of CVDs in Africa is attributed at least in part to the adoption of sedentary behaviours and unhealthy eating habits, which are linked with urbanisation and westernisation of cultures. Dietary attributes associated with CVD risk have been less investigated in Africa. However, evidence from developed nations has reported a protective effect of healthy dietary patterns such as plant-based diets (PBDs) on cardiometabolic health. The current protocol is for a review aiming to assess existing evidence on the association of PBDs with CVD risk profile in African populations. Methods and analysis This protocol was developed following the 2015 guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. We will conduct a comprehensive search of the literature for published studies on PBDs in relation to CVD risk profile in African populations. Observational studies published between January 1990 and December 2019 will be screened. A search strategy using keywords and medical subject headings terms will be applied across multiple scientific databases including PubMed-Medline, Scopus and EBSCOhost and the African Journals Online platform. Manual searches of reference lists from relevant articles will be performed. Citations will be traced using the ISI Web of Science to further identify eligible studies. Grey literature will also be screened for relevant abstracts from conference proceedings, and experts in the field will be contacted where appropriate. Two investigators will independently screen all the titles and abstracts to determine which records are eligible for full-text review. Subsequently, two investigators will review the eligible full text using the selection criteria. A third investigator will be consulted to resolve any discrepancies. Data will be extracted from studies that are eligible for the review. Meta-analysis will be performed for studies with similar or comparable methods and reported outcome measures. This will be performed overall, and by major study-level characteristics. Heterogeneity in the estimates across studies will be assessed and quantified with the use of Cochrane Q and I2 statistics, respectively. Publication biases will be investigated through funnel plots and Egger test of bias. Relevant sensitivity analyses will be performed to confirm the robustness of the findings
- ItemA method comparison study of a point-of-care blood gas analyser with a laboratory auto-analyser for the determination of potassium concentrations during hyperkalaemia in patients with kidney disease(2020-07) Chothia, Yazied; Kassum, Patricia; Zemlin, Annalise EIntroduction: Hyperkalaemia is a common electrolyte disorder that may cause life-threatening cardiac arrythmias. We aimed to determine the agreement of potassium concentrations between GEM premier 3500 point-of-care blood gas analyser (POC-BGA) and Roche Cobas 6000 c501 auto-analyser in patients with hyperkalaemia. Methods: A prospective, cross-sectional study of all consecutive adult patients referred to the Renal Unit with a serum potassium concentration ≥ 5.5 mmol/L was performed. A total of 59 paired venous blood samples were included in the final statistical analysis. Passing-Bablok regression and Bland Altman analysis were used to compare the two methods. Results: The median laboratory auto-analyser potassium concentration was 6.1 (5.9-7.1) mmol/L as compared to the POC-BGA potassium concentration of 5.7 (5.5-6.8) mmol/L with a mean difference of - 0.43 mmol/L and 95% upper and lower limits of agreement of 0.35 mmol/L and - 1.21 mmol/L, respectively. Regression analysis revealed proportional systematic error. Test for linearity did not indicate significant deviation (P = 0.297). Conclusion: Although regression analysis indicated proportional systematic error, on Bland Altman analysis, the mean difference appeared to remain relatively constant across the potassium range that was evaluated. Therefore, in patients presenting to the emergency department with a clinical suspicion of hyperkalaemia, POC-BGA potassium concentrations may be considered a surrogate for laboratory auto-analyser measurements once clinicians have been cautioned about this difference.
- ItemIncrease in blood pressure over a 7-year period in a mixed-ancestry South African population(Health & Medical Publishing Group, 2019) Davids, S. F. G.; Matsha, T. E.; Peer, N.; Erasmus, R. T.; Kengne, A. P.Background. An increase in the prevalence of high blood pressure (BP) has been reported globally and in the South African (SA) population. Objectives. To investigate temporal changes in absolute BP levels and hypertension prevalence in the mixed-ancestry South Africans. Methods. Participants were from two independent cross-sectional surveys conducted during 2008/09 (N=928) and 2014/16 (N=1 969) in Bellville South, Cape Town, SA. Participants’ eligibility was based on several criteria, including age >20 years and neither bedridden nor pregnant. Data were obtained by administered questionnaires, clinical measurements (BP and anthropometry) and biochemical assessments (oral glucose tolerance tests and cotinine levels). Known hypertension was based on a self-reported history of doctor-diagnosed hypertension and ongoing treatment. Comparison across years was based on the crude prevalence of hypertension as well as direct age-standardised prevalence, based on the SA 2011 mixed-ancestry population distribution, in 10-year age increments. Results. In all, 708 participants (76.3%) in 2008/09 and 1 488 (75.6%) in 2014/16 were female. Between 2008/09 and 2014/16, mean systolic BP increased from 124 to 136 mmHg (absolute mean difference 15 mmHg) and mean diastolic BP from 75 to 85 mmHg (absolute mean difference 9 mmHg) in the overall sample. The prevalence of screen-detected hypertension increased from 11.6% to 24.8%, with a similar increase in males and females, while the prevalence of known cases remained stable. These changes remained significant after adjustment for age and gender. Conclusions. A rightward shift in absolute BP translated into a significant increase in the prevalence of hypertension over time in this population. The predominant increases in screen-detected hypertension suggest that the deteriorating profile was not matched by efforts to detect and manage individuals with higher-than-optimal BP levels.
- ItemCase report : an index of suspicion in hyponatraemia(Hrvatsko društvo za medicinsku biokemiju, 2019) Barkhuizen, Marizna; Hoffmann, Mariza; Zöllner, Ekkehard W. A.; Erasmus, Rajiv T.; Zemlin, Annalise E.Serum indices can give valuable information and should be interpreted as a result. Lipaemia can influence results through different mechanisms, an important one being the electrolyte exclusion effect. A case of pseudohyponatraemia due to this is reported. A 15-year-old female with type 2 diabetes was seen for follow-up. Her biochemistry results revealed severe hyponatraemia of 118 mmol/L. Her capillary glucose concentration was 13.7 mmol/L with a corrected sodium of 122 mmol/L. A lipaemic index of 3+ (absolute value 1320) was noted, which was not flagged by the laboratory information system, as it was below the critical lipaemia limit for sodium determination. Repeated analysis of the same sample using a direct ion selective electrode method, the serum sodium concentration was 134 mmol/L (sodium corrected for glucose = 138 mmol/L). A triglyceride concentration was requested, which was severely raised (100.1 mmol/L). The electrolyte exclusion effect is an analytical phenomenon that causes falsely low electrolyte concentrations in the presence of severe lipaemia or hyperproteinaemia when using indirect analytical methods. These methods are used on many modern-day automated chemistry analysers and should be considered in a patient with asymptomatic hyponatraemia.