Is non-therapeutic aspirin use in children a problem in South Africa?

Background. Aspirin should not be used in children except for specific therapeutic reasons. We report on a severely ill infant who had ingested aspirin contained in a traditional medicine and review 21 other patients with pre-admission non-therapeutic salicylate exposure. Objectives and methods. We reviewed laboratory, clinical and poisons unit records to determine how many children were admitted to our hospital over an 18-month period with evidence of salicylate ingestion not prescribed for therapeutic reasons. We determined the source of the salicylate, elapsed time between ingestion and laboratory assay, morbidity and mortality and final diagnosis. Results. Twenty-one children meeting our criteria, including 9 under 6 months of age, were admitted during this period. The most prevalent source of salicylate was over-the-counter (OTC) aspirin, but some had reportedly only been given traditional medicines. Nineteen were seriously ill, 4 died and 3 had severe brain injury. Two, initially diagnosed with Reye’s syndrome, probably had inherited metabolic disorders. Only 2 patients had salicylate levels that at the time of measurement are normally considered toxic; however, the literature suggests that lower levels may exacerbate illness severity in young children. Conclusions. We found inappropriate use of OTC aspirin in children that requires explanation. There may be policy implications for the content and presentation of patient information; the incorporation of pharmaceuticals in traditional medicines merits further study. Salicylate toxicity should be considered in children with unexplained metabolic acidosis out of keeping with the severity of their acute illness

Type 2 diabetes mellitus and dyslipidaemia: effects of genetic variation in African populations

Background: Low-density lipoproteins (LDL) have been associated with damage to the cardiovascular system in patients with type 2 diabetes mellitus (T2DM). These patients are two (2X) to four (4X) times more likely to develop cardiovascular diseases (CVD) compared to non-diabetic patients due to dysfunctional lipoprotein metabolism. Normal lipid metabolism involves interconversion and transfer of molecules regulated by several enzymes such as Apolipoprotein E (ApoE) and proprotein convertase subtilisin/kexin type 9 (PCSK9). ApoE and PCSK9 are involved in clearance of lipoproteins and therefore, influence lipid profiles. Association between ApoE and T2DM in cardiovascular diseases have been widely reported. PCSK9 on the other hand is emerging as an important player in lipid metabolism but its effects in diabetes are not known. Studies on both ApoE and PCSK9 in African populations are in its infancy. Each year, CVD kills more people than any other cause of death. Many CVDs can be traced back to pathological process of atherosclerosis, in which fatty material collects along walls of arteries, limiting flexibility and obstructing blood flow. T2DM alone has been classified as a major factor for development of CVD and one of its complications is the development of dyslipidaemia. Unlike PCSK9, genetic polymorphisms in ApoE have been well characterised as important dyslipidaemia genetic markers associated with coronary artery disease. The association between ApoE and PCSK9 gene polymorphisms with dyslipidaemia in T2DM was evaluated. Diabetic dyslipidaemia presents as a triad of high triglycerides, high LDL and low high-density lipoprotein (HDL). Aims and Objectives: This study aimed to evaluate the role of genetic variation in genes coding for ApoE2 and PCSK9 on dyslipidaemia in South African diabetic patients. Main objectives’ included recruitment of participants, genetic characterisation of ApoE and PCSK9 and determination of the lipid profiles for the recruited participants. Methods: Two hundred and forty-four (n=244) participants were recruited from the Baragwaneth diabetic clinic, using a retrospective approach. The participants comprised of two groups, (i) dyslipidaemic, and (ii) non-dyslipidaemic (controls). The dyslipidaemic group was further divided into three groups; i) those with high cholesterol only, ii) those with high triglycerides only and iii) those with both high cholesterol and triglycerides which is referred to as the mixed group. Clinical and demographic parameters were retrieved from hospital records with the consent of the participants. Ethical clearance was obtained from the University of Cape Town and University of Witwatersrand. Genetic characterisation of ApoE was carried out using polymerase chain reaction (PCR) coupled to restriction fragment length polymorphism (RFLP) and confirmed through sequencing while characterisation for PCSK9 was carried out through Sanger sequencing. Results: Of the 244 participants, 165 were dyslipidaemic while 79 were not dyslipidaemic. The 165 dyslipidaemic participants were further divided into 33.3% (n=55) those with high cholesterol, 29.1% (n=48) those with high triglycerides and 37.6% and (n= 62) those with high cholesterol and triglycerides (mixed). The cohort comprised of 128 (52%) females, median (IQR) age 56.0 (48.0 – 64.0) years and 116 (48%) males with median (IQR) age of 56.5 (48.0 – 63.0) years. Most of the characteristics between the dyslipidaemic and nondyslipidaemic participants were significantly different as expected in a purposive sampling technique. ApoE3/4 genotype had the highest frequency distribution (41%) while ApoE2/3 genotype had the lowest frequency (7%). An uncharacterised ApoE referred to in the study as ApoE X with a frequency distribution of 6%, was reported for the first time. The selected measured parameters evaluated against a set of variables showed a significant association between HbA1c and age (p=<0.008) is reported. TC (p=0.00092), LDL (p=0.0184) and TG (p=0.0175) were strongly associated with poor glycaemic. Both LDL (p=0.0174 and HDL (p=0.0072) were associated with age. Homozygous ApoE2/2 and heterozygous ApoE2/3 genotypes correlated with poor glycaemic control with a median HbA1c of 10.95% (IQR 5.88-14.98%) and 10.20% (IQR 6.20-15.80%), respectively; while homozygous ApoE4/4 carriers displayed good glycaemic control with a median HbA1c of 6.60% (IQR 5.70 – 2.30%). Carriers of homozygous ApoE3/3 genotype had the highest median TC of 6.06mmol/L (IQR 5.48 -– 6.71mmol/L) while homozygous ApoE4/4 carriers had the highest median triglycerides of (2.94 (IQR 1.75 – 5.13 mmol/L). Carriers of homozygous PCSK9 rs505151 A/A (E670G) genotype had the highest frequency distribution in both groups of participants with dyslipidaemic (55.1%) and non-dyslipidaemic (63. 5%), followed by carriers of heterozygous PCSK9 rs505151G/A at 40.6% and lastly carriers of PCSK9 rs505151G/G at (9.5%). On the other hand, carriers of homozygous PCSK9 rs28362286 C/C genotype were predominantly distributed with a frequency of 94.2% and PCSK9rs28362286C/A had a very small frequency distribution of 5.8% while PCSK9rs28362286A/A was absent in this population. Carriers of PCSK9 rs505151A/A genotype had higher HbA1c with a median of 10.10% (IQR 7.48 – 12.90) compared to PCSK9 rs505151 G/A genotype with a median of 9.00% (IQR 7.03 –11.35). The results show that PCSK9 rs505151G/A with lower HbA1c had non-significantly higher TC, LDL, TG and non-HDL but lower HDL compared to PCSK9 rs505151A/A genotype. The results revealed no direct reciprocal relationship between glycaemic control and level or type of dyslipidaemia. Conclusions: The study showed the effects of ApoE and PCSK9 genetic variation on the dyslipidaemia seen in black South African diabetic participants. Therefore, this study through ApoE and PCSK9 genotypes show that the diabetic dyslipidaemia has an underlying genetic influence. In addition, to the well-characterised ApoE genotypes, an uncharacterised genotype referred to as ApoE X genotype is reported. With these findings, consideration to explore possible underlying genetic predisposition is recommended especially in diabetic patients with dyslipidaemia that responds poorly to standard therapy

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic.Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p &lt; 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p&lt;0.0001 with the smaller species being much higher during pregnancy.Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but mayindicate a predisposition to atherosclerosisKeywords: Apolipoprotein E. Lipids, pregnancy, small dense LDL species, African.Due to errors in the previous PDF especially in the 'Cite as' authors names, the PDF fulltext has been reloaded. This information is now correct

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol. ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity. The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p &lt; 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p&lt;0.0001 with the smaller species being much higher during pregnancy. Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosi

Implementation of POCT in the diabetic clinic in a large hospital

Aim: Point-of-care testing (POCT) is gaining renewed interest, especially in resource-limiting primary health care, due to rise in prevalence of communicable and non-communicable diseases hence POCT needscontinuous appraisal. Methods: Random glucose and glycated haemoglobin (HbA1c) were measured in 104 diabetic patients using standard laboratory multichannel analyzer 917. The utility of venous blood compared to capillary blood in measuring HbA1c was evaluated in a subset of 20 patients using a POCT device, DCA Vantage. Lastly, the POCT was validated against the laboratory multichannel analyser 917, in measurement of HbA1c in a second subset of 46 patients. Results: Random blood glucose levels and HbA1c levels moderately correlated (r2 = 0.56; p &lt; 0.0001). Random glucose tests showed that 41% of the patients had poor glycaemic control while HbA1c showed 74%. Venous and capillary blood in HbA1c showed strong correlation (r2 = 0.89440; p &lt; 0.001. There was also strong correlation (r = 0.9802; p &lt; 0.0001) in HbA1c measured using the DCA Vantage and the standard laboratory analyser, Multichannel Analyser 917. Conclusion: Venous or capillary blood can be used in POCT for HbA1c. POCT is ideal for monitoring glucose control and management of diabetes in resource-limited countries such as South Africa

Apolipoprotein E variants, plasma lipids, lipoproteins and dysApolipoprotein E variants, plasma lipids, lipoproteins and dysβLipoproteinaemia during pregnancy in Zimbabwean women.

Includes bibliographical references (leaves 117-138).This study of pregnant women in Zimbabwe therefore set itself the following aims: To describe lipid and lipoproteins during and after pregnancy, To examine the prevalence of apoE variants, To evaluate dysβlipoproteinaemia in pregnancy, The correlation between dysβplipoproteinaemia and the apoE genotypes. This is the first study to systematically examine lipids and lipoproteins during pregnancy in black Africans

Is non-therapeutic aspirin use in children a problem in South Africa?

Background. Aspirin should not be used in children except for specific therapeutic reasons. We report on a severely ill infant who had ingested aspirin contained in a traditional medicine and review 21 other patients with pre-admission non-therapeutic salicylate exposure. Objectives and methods. We reviewed laboratory, clinical and poisons unit records to determine how many children were admitted to our hospital over an 18-month period with evidence of salicylate ingestion not prescribed for therapeutic reasons. We determined the source of the salicylate, elapsed time between ingestion and laboratory assay, morbidity and mortality and final diagnosis. Results. Twenty-one children meeting our criteria, including 9 under 6 months of age, were admitted during this period. The most prevalent source of salicylate was over-the-counter (OTC) aspirin, but some had reportedly only been given traditional medicines. Nineteen were seriously ill, 4 died and 3 had severe brain injury. Two, initially diagnosed with Reye’s syndrome, probably had inherited metabolic disorders. Only 2 patients had salicylate levels that at the time of measurement are normally considered toxic; however, the literature suggests that lower levels may exacerbate illness severity in young children. Conclusions. We found inappropriate use of OTC aspirin in children that requires explanation. There may be policy implications for the content and presentation of patient information; the incorporation of pharmaceuticals in traditional medicines merits further study. Salicylate toxicity should be considered in children with unexplained metabolic acidosis out of keeping with the severity of their acute illness