scholarly journals Application of benchmark analysis for mixed contaminant exposures: Mutual adjustment of two perfluoroalkylate substances associated with immunotoxicity

2017 ◽  
Author(s):  
Esben Budtz-Jøergensen ◽  
Philippe Grandjean,
Keyword(s):  
Serum Concentrations ◽  
Postnatal Exposure ◽  
Confidence Bounds ◽  
Igg Antibody ◽  
Benchmark Analysis ◽  
Equal Degree ◽  
Related Substances ◽  
Before And After ◽  
Childhood Vaccines ◽  
Lower Confidence Bounds

AbstractBackgroundDevelopmental exposure to perfluorinated substances is associated with deficient IgG antibody responses to childhood vaccines as an indication of depressed immune system functions. As this outcome may represent a critical effect of these substances, calculation of benchmark dose (BMD) results would be useful for standards setting to protect exposed populations against adverse effects. However, in the mixed exposure setting of most epidemiological evidence, the two major and inter-related substances associated with this adverse effect have shown similar benchmark results that raise concerns about possible confounding.MethodsWith the aim of better characterizing the immunotoxicity impact of the two major perfluorinated substances in the mixed exposures, we carried out BMD calculations on prospective data from two prospective birth cohort studies from the Faroe Islands with a total of 1,146 children. Exposure data included serum concentrations of perfluorooctane sulfonate and perfluorooctanoate at birth and at age 5 years and, as outcome parameters, the serum concentrations of specific IgG antibodies against tetanus and diphtheria at ages 5 and 7. We calculated the BMDs and their lower confidence bounds (BMDLs) and included mutual adjustment for the two compounds.ResultsThe BMDLs for the two immunotoxicants were of similar magnitude before and after adjustment. Both substances showed lower results for a logarithmic dose-response model, which also provided a slightly better fit than a linear dose model for both antibodies. We also used a broken curve shape that allowed a different slope below the median exposure. Postnatal exposure as represented by the age 5 serum concentration, showed a stronger association with the antibody outcomes than the prenatal exposure. Due to the correlation between the two immunotoxicants, the mutual adjustment resulted in elevated BMD results and p values. However, the BMDL values were virtually unchanged.ConclusionsAdjustment for co-exposure to another immunotoxicant increased the variance and the BMD values, but affected the BMDL values only to a negligible extent. These calculations are in accordance with an interpretation that, when two toxicants appear to affect an outcome to an almost equal degree and none of them is known to be solely responsible, the exposures should both be considered responsible and attract equal regulatory attention until further evidence shows otherwise.

scholarly journals Using geospatial models to map zero-dose children: factors associated with zero-dose vaccination status before and after a mass measles and rubella vaccination campaign

2021 ◽  
Author(s):  
Rohan Arambepola ◽  
Yangyupei Yang ◽  
Kyle Hutchinson ◽  
Francis D Mwansa ◽  
Julie Ann Doherty ◽  
...  
Keyword(s):  
Vaccination Campaign ◽  
Fine Scale ◽  
Healthcare Facilities ◽  
Factors Associated ◽  
Catchment Areas ◽  
Before And After ◽  
Childhood Vaccines ◽  
A Prospective Study ◽  
Vaccination Campaigns ◽  
The Impact

Introduction: Despite gains in global coverage of childhood vaccines, many children remain undervaccinated. Vaccination campaigns also known as Supplemental Immunization Activity (SIA) are commonly conducted to reach those who are undervaccinated. However, reaching these children even during an SIA is challenging. We evaluated the effectiveness of an SIA in reaching zero dose children. Methods: We conducted a prospective study in 10 health center catchment areas in Southern province, Zambia in November 2020. About 2 months before the measles and rubella SIA we developed aerial satellite maps which were then used to enumerate and survey households. Zero dose children were identified during this exercise. After the SIA, households with zero dose children identified before the SIA were targeted for mop up vaccination and to assess if they were vaccinated during the SIA. A Bayesian geospatial model was used to identify factors associated with zero-dose status before the campaign and produce fine-scale prevalence maps. Models were used to identify factors associated with measles zero-dose children reached in the campaign and identify optimal locations for additional vaccination sites. Results: Before the vaccination campaign, 4% of children under 9 months were DTP zero-dose and 17% of children 9-60 months were measles zero-dose. Of the 461 measles zero-dose children identified before the vaccination campaign, 338 (73.3%) were vaccinated during the campaign, 118 (25.6%) were reached by a targeted mop-up activity. The presence of other children in the household, younger age, greater travel time to health facilities, and living between health facility catchment areas were associated with zero-dose status. Mapping zero-dose prevalence revealed substantial heterogeneity, both within and between catchment areas. Several potential locations were identified for additional vaccination sites. Conclusion: Fine-scale variation in zero-dose prevalence and the impact of accessibility to healthcare facilities on vaccination coverage were identified. Geospatial modeling can aid targeted vaccination activities.

Lack of Oxidative Damage in Serum Polyunsaturated Fatty Acids before and after Dialysis in Chronic Uremic Patients

1989 ◽  
Vol 12 (8) ◽  
pp. 515-518 ◽  
Author(s):  
M. Taccone-Gallucci ◽  
R. Lubrano ◽  
A. Belli ◽  
G. Citti ◽  
M. Morosetti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oxidative Damage ◽  
Polyunsaturated Fatty Acids ◽  
Fatty Acid Pattern ◽  
Chronic Hemodialysis ◽  
Serum Concentrations ◽  
Serum Fatty Acid ◽  
Before And After ◽  
Uremic Patients ◽  
Mononuclear Blood Cells

We described previously that in the erythrocytes and mononuclear blood cells from uremic patients on chronic hemodialysis, the membrane concentrations of malonyldialdehyde (MDA), resulting from peroxidation of polyunsaturated fatty acids (PUFA) in the membrane itself increased, and the concentrations of vitamin E (VIT E), the major antioxidizing agent, were lower. In the present study we analysed whether similar oxidative damage is seen in the serum from hemodialysis patients and whether the serum fatty acid pattern is affected. No evidence was found of oxidative damage in the serum during hemodialysis, serum concentrations of MDA and VIT E remaining constant before and after dialysis. No change was observed in serum pattern of PUFA, particularly linoleic acid. We therefore assume that the oxidative damage described in uremic patients is mainly intracellular.

Management of posaconazole-induced pseudohyperaldosteronism

2020 ◽  
Vol 75 (12) ◽  
pp. 3688-3693
Author(s):  
Matthew R Davis ◽  
Minh-Vu H Nguyen ◽  
Thomas J Gintjee ◽  
Alex Odermatt ◽  
Brian Y Young ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Dose Reduction ◽  
Serum Potassium ◽  
Continuous Monitoring ◽  
Therapeutic Interventions ◽  
Serum Concentrations ◽  
Average Decrease ◽  
Before And After ◽  
Repeat Assessment

Abstract Background Posaconazole-induced pseudohyperaldosteronism (PIPH) has been associated with elevated posaconazole serum concentrations. Clinicians are faced with the difficult task of managing patients with PIPH while maintaining the efficacy of antifungal therapy. Commonly, modifications to posaconazole therapy are utilized in managing PIPH, including dosage reduction of posaconazole or switch to an alternative antifungal. Objectives To characterize the management of patients diagnosed with PIPH and their response to various therapeutic interventions. Methods We retrospectively reviewed 20 consecutive adult patients diagnosed with PIPH. Patient data collected included blood pressure, electrolytes, endocrine laboratory values and posaconazole serum concentrations collected before and after therapeutic intervention. Results Of 20 patients included, 17 patients (85%) underwent therapeutic modification, with posaconazole dose reduction (n = 11) as the most common change. Other modifications included discontinuation (n = 3), switch to an alternative antifungal (n = 2) and addition of spironolactone (n = 1). Clinical improvement (decrease in systolic blood pressure and increase in serum potassium) was observed in 9 of 17 patients (52.9%). An average decrease in systolic blood pressure of 7.1 mmHg and increase in serum potassium of 0.22 mmol/L was observed following therapeutic modification. Conclusions We report our experience with PIPH management, for which there is no universally effective strategy. We utilized a stepwise approach for management, starting with posaconazole dose reduction and repeat assessment of clinical and laboratory parameters. If resolution of PIPH is not achieved, an alternative triazole antifungal or the addition of an aldosterone antagonist are additional potential interventions. It is possible for PIPH to persist after therapeutic modification despite these interventions. Thus, early diagnosis and continuous monitoring is warranted.

scholarly journals Effect of a Padel Match on Biochemical and Haematological Parameters in Professional Players with Regard to Gender-Related Differences

2020 ◽  
Vol 12 (20) ◽  
pp. 8633
Author(s):  
Francisco Pradas ◽  
Alejandro García-Giménez ◽  
Víctor Toro-Román ◽  
Bernardino Javier Sánchez-Alcaraz ◽  
Nicolae Ochiana ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Fluid Intake ◽  
Serum Concentrations ◽  
Protein Catabolism ◽  
Glutamic Oxaloacetic Transaminase ◽  
Before And After ◽  
Baseline Values ◽  
Ad Libitum ◽  
High Level ◽  
Match Effect

Haematological and biochemical parameters have not yet been analysed in professional padel players. The aim of this study was to determine the basal values of these parameters and to observe the effect of a simulated competition on them, including gender-related differences. A total of 14 male professional players (age: 28.2 ± 7.9 years), and 16 female professional players (age: 29.7 ± 3.7 years) participated in this study. Players were allowed to hydrate ad libitum during the matches. Haematological and biochemical values were obtained before and after a simulated competitive padel match. The men’s group showed higher baseline values in red blood cells, haematocrit, haemoglobin, urea, creatinine, uric acid, albumin, glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH) and creatine kinase (CK) (p < 0.01) than the women’s group. Attending to match effect, significant differences were obtained in urea, creatinine, CK and glucose (p < 0.05). Finally, the group x match interaction revealed significant differences in serum concentrations of sodium and chloride (p < 0.05). In conclusion, high-level padel matches provoke several changes in biochemical parameters related to muscle damage and protein catabolism. Recovery and fluid intake strategies could be added regarding gender. The results obtained could be due to the differences in the intensity and volume of the simulated competition.

Altered serum levels of thyroxine, triiodothyronines and diiodothyronines in endogenous depression

1981 ◽  
Vol 96 (2) ◽  
pp. 199-207 ◽  
Author(s):  
C. Kirkegaard ◽  
J. Faber
Keyword(s):  
Similar Pattern ◽  
Serum Levels ◽  
Endogenous Depression ◽  
Serum Concentrations ◽  
Electroconvulsive Treatment ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Before And After ◽  
Altered Serum

Abstract. Serum levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were studied in 80 patients with endogenous depression before and after electroconvulsive treatment (ECT). Compared to the values found after recovery, the patients when depressed had significant increased serum levels of T4, rT3, 3,3'-T2 and 3',5'-T2. Serum concentrations of T3 and 3,5-T2 were not significantly altered. Similarly the free T4 index (FT4I) was increased, while the free T3 index (FT3I) was unaffected. Previous studies have shown a reduced TSH response to TRH in patients with endogenous depression and that the long-term outcome after ECT is strongly related to changes in the TSH response. However, patients with increased TSH response to TRH (n = 23) had a pattern of serum iodothyronine concentrations similar to those (n = 57) with an unchanged TSH response. A similar pattern was also found in 7 patients with non-endogenous psychosis, in whom the TSH response to TRH was unchanged after recovery. It is concluded that the alterations of the TSH response to TRH found in endogenous depression cannot be explained by changes of FT4I or FT3I.

scholarly journals Concentration of Serum Thyroid Hormone Binding Proteins after 131I Treatment of Hyperthyroidism

1981 ◽  
Vol 18 (4) ◽  
pp. 211-214 ◽  
Author(s):  
John S Harrop ◽  
Malcolm R Hopton ◽  
John H Lazarus
Keyword(s):  
Thyroid Hormone ◽  
Binding Proteins ◽  
Response To Treatment ◽  
Serum Concentrations ◽  
Hormone Binding ◽  
Thyroxine Binding Globulin ◽  
131I Treatment ◽  
Before And After ◽  
Hormone Binding Protein ◽  
Serum Thyroid Hormone

Serum concentrations of the thyroid hormone binding proteins, thyroxine binding globulin, prealbumin, and albumin were determined in 30 thyrotoxic patients before and after 131I treatment. Each patient was placed into one of three groups according to response to treatment. The serum concentration of all three proteins rose significantly in 10 patients who became euthyroid, and a greater increase was seen in 10 patients who developed hypothyroidism. There was no significant change in thyroid hormone binding protein concentrations in 10 subjects who remained hyperthyroid. Changes in the concentration of thyroid hormone binding proteins should be borne in mind when total thyroid hormone concentrations are used to monitor the progress of patients receiving treatment for hyperthyroidism.

Agreement among High School Diving Judges

1982 ◽  
Vol 55 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Michael J. Stewart ◽  
William O. Blair
Keyword(s):  
High School ◽  
Confidence Intervals ◽  
Intraclass Correlation ◽  
Confidence Bounds ◽  
Point Estimates ◽  
Lower Confidence ◽  
Relative Consistency ◽  
Position Type ◽  
Lower Confidence Bounds ◽  
Actual Point

The analysis of aesthetic sports by a panel of judges has received some attention in past literature, but more studies have employed interclass correlations to arrive at judges' agreement or relative consistency. The purpose of this study was to determine raters' agreement and relative consistency of five male diving judges at the Kansas State Boys' Swimming and Diving Championships using intraclass correlation. Furthermore, one-sided confidence intervals were formed for analysis of sample variance. A total of 249 dives were performed and these dives were categorized into 16 position × type combinations for the analysis. Judges' variance was significant for 5 of the 16 type × position combinations. As expected divers' variance was significant for 14 of the 16 type × position combinations. Judges appeared to be somewhat consistent across dives but they were unable to agree upon the score of each dive. In other words the point estimates for consistency were generally greater than the point estimates for raters' agreement. Yet in neither case, consistency or raters' agreement, were lower confidence bounds impressively close to the actual point estimates.

Feasibility of Measuring 5-Fluorouracil Catabolic Potential by Oral Loading

2005 ◽  
Vol 33 (5) ◽  
pp. 501-506 ◽  
Author(s):  
S Watabe ◽  
H Sengoku ◽  
K Kawai ◽  
M Matsuda ◽  
K Sakamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Side Effects ◽  
Load Test ◽  
Serum Concentrations ◽  
Optimum Conditions ◽  
Continuous Administration ◽  
Individual Variations ◽  
Before And After ◽  
Catabolic Potential ◽  
Simple Evaluation

The efficacy of 5-fluorouracil (5-FU) treatment and the incidence of adverse events differ among patients and depend to some extent on individual variations in drug catabolism. This feasibility study aimed to determine the optimum conditions for a 5-FU oral load test, which would allow the simple evaluation of individual differences in 5-FU catabolism. Patients with colon cancer were given oral 5-FU (200 mg/day) for 3 days ( n = 36) or a single 100 mg dose ( n = 14). Serum concentrations of uracil, dihydrouracil, 5-FU and 5-fluoro-5, 6-dihydrouracil were measured before and after 5-FU administration. The results suggested that a decline in 5-FU metabolism was associated with continuous administration and increasing age. We conclude that a continuous load of 5-FU is necessary in order to predict the efficacy and side-effects of the drug. The 3-day regimen, with its ease of administration, merits further study to assess its possible clinical application.

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