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BACKGROUND: Researchers recently created a new scoring system for characterizing organ dysfunction in critically ill pediatric patients, named the pSFOA (pediatric sequential organ failure assessment). Support for applying this scoring system in pediatric patients who suffer from cyanotic and acyanotic congenital heart diseases has not been evaluated. OBJECTIVES: To compare the pSOFA scores between pediatric patients with acyanotic and cyanotic congenital heart disease (CHD). Exampine the pSOFA results of CHD patients with pediatric patients who underwent hematopoietic stem cell transplantations. METHODS: A retrospective case-study of pediatric patients with congenital heart disease admitted to the CICU at Boston Children’s Hospital in 2018. Patients were included if between 1 and 5 years of age, neonates of less than a month old were excluded. A total of 101 patients were reviewed, 50 with cyanotic CHD and 51 with acyanotic CHD. Patient vital signs were assessed using the pSOFA scoring system, with scores assigned based on indices of respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal system function. Scores were analyzed using two-tailed nonparametric Mann-Whitney tests with an alpha of 0.05. The pSOFA scores of CHD patients were then compared to patients who were admitted to the ICU at Boston Children’s Hospital after they received a hematopoietic stem cell transplantation (HSCT). Dunn’s multiple comparisons tests were performed for the two CHD groups and the HSCT patients. An alpha value of 0.05 was also used for these tests. RESULTS: Parameters determined to be statistically significant between the cyanotic and acyanotic CHD patients were, Total High Direct score, Total Average Direct score, Total Low Indirect Score, Total High Indirect score, Neurologic High score, Average Neurologic score, Renal High score, Average Renal score, and Hepatic Low Indirect score. The parameters that were statistically different between the CHD groups and the HSCT group were Age, Maximum Coagulation, Maximum Renal, Maximum Hepatic, and Maximum Total pSOFA scores. Parameters that were significantly different only between cyanotic CHD and HSCT were Maximum Cardiovascular and Maximum Respiratory. Scores that were significantly different between acyanotic CHD and HSCT were Maximum Neurologic. CONCLUSIONS: There were significant differences in pSOFA scores between children with cyanotic CHD and acyanotic CHD, specifically regarding total direct, total indirect, neurologic, and renal scores. Additional research is required to explain these scores differences and validation of these scores in predicting morbidity and mortality outcomes in these patient populations. / 2022-06-02T00:00:00Z

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Coronary Heart Disease (CETO) is one of the most common causes of mortality in industrialised societies, and it has been demonstrated elsewhere that shift workers have an increased risk of developing CHD compared to day-workers. One possible explanation for this increased risk is that a shift worker may show inappropriate postprandial responses to a night-time meal, when their biological clock is not adapted to the night shift. This could lead to an elevation in the circulating levels of certain hormones and metabolites, such as triacylglycerol (TAG) and insulin, which are known to be risk factors for CHD. This thesis investigated the relationships between meal times and postprandial hormone and metabolic responses in simulated and real-life shift-workers. The work is presented as three major clinical trials. In the first of these, a combination of timed bright light and darkness/sleep was used to induce a gradual 9-hour phase advance in 12 healthy subjects, who then underwent a rapid 9-hour phase delay. Three meal study days were arranged, to occur during the baseline condition, immediately after the rapid phase delay, so that the subjects effectively had "simulated jet lag", and two days later. Blood parameters measured included plasma glucose, insulin, proinsulin, C-peptide, non-esterified fatty acids (NEFA), TAG and glucose- dependent insulinotropic polypeptide (GIP). Substantial differences in plasma TAG and NEFA were observed in the postprandial responses when the subjects consumed an identical meal immediately after the rapid phase delay, compared with during the baseline conditions. Two days after the rapid phase delay, subjects showed inteimediate hormone and metabolite levels, suggesting that the biological clock had a major effect on these postprandial responses. In the second study, day and night-time postprandial responses were compared in a simulated shift work environment, and the effectiveness of a number of potentially beneficial procedures was investigated. These included alterations to the content of the meal consiraied prior to the night shift, bright light exposure during the night shift, and a daytime rest period prior to the night shift. As in the first study, significant differences were seen in a number of hormones and metabolites on the night shift. compared with during the day. The content of the previous meal, bright light exposure and a daytime rest period prior to the night shift all had significant effects on the night-time postprandial responses. The most exciting discovery made was that a single 8-hour night-time bright light exposure significantly lowered the TAG postprandial responses on the simulated night shift. As all the work conducted up until this point had utilised simulated conditions, it was important to illustrate that similar differences in postprandial responses at night-time could be demonstrated in "real-life shift workers". Thus, nine midwives were recruited from the Royal Surrey County Hospital, and studied on four occasions. This allowed comparison of postprandial responses on both day and night shifts, and also allowed further investigation of the effect of altering the content of the previous meal. Significant differences were again found in a number of blood parameters when the night-time and day-time responses to the test meal were compared, with the most striking being a delayed NEFA rise on the night shift, compared with during the day. In conclusion, this series of studies have illustrated that the human body responds differently to a meal consumed at night-time, compared with during the day, both in a simulated and a real-life environment. This results in variations in the levels of a number of known CHD risk factors, and may be linked with the elevated CHD risk reported in shift workers. Alteration to the meal prior to the night shift, exposure to bright light during the night shift, and instituting a rest period prior to the night shift, were all shown to be potentially beneficial in reducing the variation between day and night-time responses.

Humic substances are a group of ubiquitous compounds formed during the decay of plant and animal residues in the environment. These substances can be divided into humic acid, fulvic acid and humin on the basis of its solubility in water as a function of pH. Fulvic acid is the fraction that is soluble in water under all pH conditions and is usually extracted from brown coal and is therefore associated with high levels of heavy metals. These heavy metal levels have become a point of concern and a unique method for synthesizing fulvic acid from a carbohydrate source has been subsequently developed and patented in an attempt to address this problem. The purpose of this study was therefore, to test the topical and systemic safety and efficacy of this new carbohydrate derived fulvic acid (CHD-FA) product. Initial in vitro screening using the Kirby-Bauer disk diffusion method indicated that the product was active against the Staphylococcus aureus test organisms used (ATCC 12600 and P3938). Results showed that not only was it as effective as the oxacillin control, but in the case of a more virulent strain of S. aureus, the CHD-FA (3.9% w/v) proved more active. Subsequently, the ability of the product to cross full-thickness skin was ascertained using Franz-type diffusion cells fitted with 100ìm skin disks obtained from rats. At the end of a 12-hr period, results indicated that up to 20% of the CHD-FA at a pH of 2.9 was able to cross the skin barrier. Divided into 6 phases, extensive animal safety studies were conducted on the product. In phase I, toxicity and sensitivity to topical application was examined by applying the product to the ears of mice over a period of 30 days. Phase II and III was undertaken to study the long term effects (6-weeks and 6-months) of CHD-FA ingestion (150 mg/kg body mass) whilst phase IV tested the effects of CHD-FA ingestion on pregnant rats and their off-spring. Phase V was an acute toxicity study in which rats received a single oral dose of CHD-FA (150mg/kg bw) and then observed for a period of 7 days. Phase VI was a 6-week chronic study in which the animals received 100mg/kg bw daily for the duration of the experiment. Results obtained in all studies showed that CHD-FA is safe for topical as well as, oral use at the doses tested. In addition, it is safe for use during pregnancy. Finally, the in vivo anti-microbial efficacy of the CHD-FA was examined using an infected wound healing model. A pilot study indicated that the animals used should be immunocompromised and the wounds inoculated with a Staphylococcus aureus (ATCC 12600) concentration of 1x1010 CFU/ml. Results from the main study showed that topical applications of the CHD-FA (pH 1.98) product at a concentration of 1.75% w/v over the 5-day period produced a wound healing pattern similar to that of the positive fuscidic acid control. In contrast, animals receiving an oral treatment of the product did not produce a pattern different from that of the water control group. In conclusion, CHD-FA has been shown to be safe and effective in treating S. aureus infections in vitro and in animal models. This study indicates that the next phase of human studies is certainly warranted. / Dissertation (MSc)--University of Pretoria, 2009. / Pharmacology / unrestricted

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