Meta-analysis of small for gestational age births and disinfection byproduct exposures.

BACKGROUND: Some epidemiological studies show associations between disinfection byproducts (DBPs) and adverse developmental outcomes. OBJECTIVES: We undertook a meta-analysis of epidemiological studies on maternal exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) and risk of small for gestational age (SGA) birth. METHODS: We identified forty-five publications including two reports and five theses via a 2020 literature search. Nineteen study populations from 16 publications met the inclusion criteria and were systematically evaluated. Effect measures were pooled using random effects meta-analytic methods along with cumulative, sub-group and meta-regression analyses to examine between-study heterogeneity and variation in risk across different DBP measures. RESULTS: We detected a small increased risk for SGA with exposure to the sum of four (i.e., THM4) THM4 (odds ratio (OR) = 1.07; 95%CI: 1.03, 1.11), chloroform (OR = 1.05; 95%CI: 1.01, 1.08), bromodichloromethane (OR = 1.08; 95%CI: 1.05, 1.11) and the sum of the brominated THM4 (OR = 1.05; 95%CI: 1.02, 1.09). Larger ORs were detected for the sum of five haloacetic acids (i.e., HAA5) (OR = 1.12; 95%CI: 1.01, 1.25), dichloroacetic acid (OR = 1.25; 95%CI: 1.01, 1.41) and trichloroacetic acid (OR = 1.21; 95%CI: 1.07, 1.37). We detected larger SGA risks for several THM4 among the prospective cohort and case-control studies compared to retrospective cohorts and for the SGA3/5% (vs. SGA10%) studies. The THM4 meta-regression showed associations between SGA and the total quality score based on categorical or continuous measures. For example, an OR of 1.03 (95%CI: 1.01, 1.06) was detected for each 10-point increase in the study quality score based on our systematic review. CONCLUSIONS: We detected a small increased risk of SGA based on 18 THM4 study populations that was comparable to a previous meta-analysis of eight THM4 study populations. We also found increased risks for other THM4 and HAA measures not previously examined; these results were robust after accounting for outliers, publication bias, type of SGA classification, different exposure windows, and other factors.

Lung transplantation as rescue therapy in patients too sick to be discharged from acute care.

BACKGROUND: There is an increasing demand for lung transplantation in patients in advanced respiratory failure. Although many of these patients do not require mechanical ventilation or extracorporeal membrane oxygenation, an increasing number are critically ill. In this single-center study, we have analyzed our experience with lung transplantation in subjects who were inpatients at the time of their transplant and not expected to survive to discharge. METHODS: Between July 2006 and March 2012, we performed 274 bilateral sequential lung transplants and 34 single-lung transplants. Twenty-six patients who were inpatients at the time of their transplant, and were not expected to survive to hospital discharge, formed the inpatient group in this retrospective review. The remaining 281 outpatient lung transplant patients formed the comparison group. RESULTS: The inpatient group spent significantly fewer days on the waiting list compared to the outpatient group. Postoperative survival was significantly poorer in the inpatient group compared to the outpatient group (P = .001), and this was most noticeable in the first 90 days. There was no significant difference in survival between the inpatient transplant cohort and a historically comparable wait list cohort (P = .614). CONCLUSION: Lung transplantation in critically ill inpatients, although associated with a survival advantage compared to not transplanting them, does give poorer survival results compared to postoperative survival in outpatient patients.

Age-specific differences in binding of heparin to plasma proteins.

BACKGROUND: Clinically significant age-related differences in the anticoagulation effect of heparin have previously been established in vitro as well as in different clinical settings in vivo. These differences were hypothesized to be due to the age-specific differences in binding of heparin to plasma proteins. OBJECTIVES: The aim of this project was to investigate global age-related differences in heparin binding to plasma proteins. PATIENTS/METHODS: Heparin-binding proteins were identified by incubating heparin-coated magnetic beads with plasma samples from neonates, children and adults, and purifying the proteins that were bound to the beads in this reaction system. RESULTS: These results provide the first preliminary evidence of age-related differences in the total number and concentration of proteins bound to heparin. The results also suggest, for the first time, that there are age-related differences of heparin binding to antithrombin and thrombin. CONCLUSIONS: The results of this study, although preliminary, support and contribute to the explanation of the mechanism of age-related differences in the effect of heparin observed previously in vitro and in vivo.

The effect of different snake venoms and anti-venoms on thrombin clotting time in human plasma.

BACKGROUND: Crotaline snake species, or pit vipers, are distributed throughout Asia and America. While much is known about the clinical effect of these snake venoms, there is a lack of evidence related to the various anti-venoms available and their effectiveness in reversing the effect of different venoms. AIM: This study aimed to determine the interaction of the venoms of the following species: Crotalus unicolor, Crotalus adamanteus, Crotalus vegrandis, Trimeresurus spp, Calloselasma rhodostoma, Bothriechis schlegelii and Agkistrodon and the following anti-venoms: Anticrotalico, Antivipmyn, Antibotropico, Antifidico and SAIMR by evaluating their effect on the thrombin clotting time in human plasma. METHOD: The interactions of venoms and anti-venoms were evaluated using thrombin clotting time in human plasma. RESULTS: The results demonstrate that Anticrotalico anti-venom was most effective for the Crotalid species (Crotalus unicolor, Crotalus adamanteus, Crotalus vegrandis). Anticrotalico extended the time to clot formation 2.7 fold for Crotalus Unicolor, 3 fold for Crotalus Adamanteus and 4.6 fold for Crotalus Vegrandis. The anti-venoms most efficient in reversing the effect of the Trimeresurus spp venom, were Anticrotalico, Antivipmyn, Antibotropico and Antifidico anti-venoms, which all completely reversed the effect of clot formation as evident by no clot formation within the 999 seconds measurement limit. Bothriechis schlegelii venom was neutralized by all anti-venoms tested. Calloselasma rhodostoma venom was neutralized by Antifidico as well as Anticrotalico. The most efficient anti-venoms against the Agkistrodon venom were Anticrotalico and Antibotropico. In general, monovalent anti-venoms had improved efficiency for their corresponding snake species, depending highly on the composition of the snake venom. This study confirms the importance of considering the choice of anti-venom in a clinical setting, to reverse the effect of specific snake venoms. In addition, this study suggests that some anti-venoms can be considered for use against a variety of snake-venoms.

Age-related plasma reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4.

This study was conducted to establish age-related reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4 (PF4)--and to determine if the quantitative values of these proteins may contribute to the reported age-dependent effect of unfractionated heparin (UFH). Plasma samples were obtained from healthy children aged between 1 month and 16 years and from healthy adult volunteers. Two commercial kits were used to measure plasma vitronectin and PF4 levels. Results were reported as mean and boundaries including 95% of the population. Plasma vitronectin levels for children aged 1-5 years were significantly higher compared with adults. Plasma PF4 levels for infants <1 year of age were significantly lower compared with adults. The differences between reference values for both proteins in all other age-groups were not statistically significant. This study for the first time has established age-related reference ranges for vitronectin and PF4. In establishing these ranges, the quantitative values of these proteins do not appear to be the major contributory cause for the age-dependent variation in UFH effect. Future studies are required to evaluate the possible impact of age-dependent differences in binding between heparin-binding proteins and UFH.

Refinement and feasibility testing of a manual micro-method for protamine titration.

Current clinical recommendations for unfractionated heparin (UFH) therapy suggest target APTT ranges should reflect heparin concentrations of 0.2-0.4 IU/ml by protamine titration or 0.35-0.7 IU/m by an anti-Xa assay. Historically, performance of a manual protamine titration assay has been labour intensive and required a large plasma sample. However, recent studies have described difficulties with standardizing anti-Xa assays and demonstrated poor correlation of anti-Xa assays in children. This study aimed to refine and test the feasibility of a modified protamine titration assay using 100 microl of plasma. The resultant method produced reliable and repeatable results in adult plasma pools spiked with UFH. The feasibility of this method was proven by testing of in vivo heparinised samples obtained from children. This protamine titration method may offer an alternative to anti-Xa assays for clinical monitoring of children on heparin therapy, and will enhance clinical studies investigating paediatric-specific management of UFH therapy.

The differences of platelet response to snake venoms: a comparative study of children and adults.

Platelets play a vital role in the coagulation, yet the potential for differences in platelet function, between adults and children, remains underexplored. This is despite the age-related variation in haemostatic proteins, that is encompassed by the term Developmental Haemostasis. Hemotoxins found in the venoms of Australian snakes mimic human blood coagulation factors. The effects of Australian snake venoms on platelets, as well as the possible differential response in adults and children were subject of this study.

Thrombin generation: the functional role of alpha-2-macroglobulin and influence of developmental haemostasis.

Currently available chromogenic and fluorogenic substrates for endogenous thrombin potential (ETP) measurement are cleaved by both free (active) and alpha-2-macroglobulin-bound (inactive) thrombin, leading to an overestimation of ETP. Commercial methods for ETP measurement determine this using a mathematical algorithm, which assumes the contribution of alpha-2-macroglobulin to the ETP. This limits application of such methods to populations where variation in alpha-2-macroglobulin concentrations is observed, primarily children. This study examined the contribution of alpha-2-macroglobulin-bound thrombin to the ETP measurement in neonates, children and adults, to determine whether automated methods are appropriate for use in neonates and children.