Key Opportunities to Replace, Reduce, and Refine Regulatory Fish Acute Toxicity Tests.

Fish acute toxicity tests are conducted as part of regulatory hazard identification and risk-assessment packages for industrial chemicals and plant protection products. The aim of these tests is to determine the concentration which would be lethal to 50% of the animals treated. These tests are therefore associated with suffering in the test animals, and Organisation for Economic Co-operation and Development test guideline 203 (fish, acute toxicity) studies are the most widely conducted regulatory vertebrate ecotoxicology tests for prospective chemical safety assessment. There is great scope to apply the 3Rs principles-the reduction, refinement, and replacement of animals-in this area of testing. An expert ecotoxicology working group, led by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research, including members from government, academia, and industry, reviewed global fish acute test data requirements for the major chemical sectors. The present study highlights ongoing initiatives and provides an overview of the key challenges and opportunities associated with replacing, reducing, and/or refining fish acute toxicity studies-without compromising environmental protection. Environ Toxicol Chem 2020;39:2076-2089. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Preliminary findings: 25(OH)D levels and PTH are indicators of rapid bone accrual in pubertal children.

OBJECTIVE: The objective of this study was to evaluate the role of serum levels of 25(OH)D and PTH on the accumulation of whole body bone mass in a cohort of children. METHODS: This was a longitudinal study (1.98 +/- 0.07 y) of sixty-nine children (89% Caucasian, 44% male) enrolled in a calcium supplementation trial. Bone area, bone mineral content (BMC) and density (BMD) of the whole body and radius were assessed using a QDR 2000 (Hologic, Inc) dual energy x-ray absorptiometer. Serum PTH and 25(OH)D were measured using radioimmunoassays. RESULTS: Vitamin D stores were inversely related gain in bone area (p < 0.002), BMC (p < 0.002) BMD (p < 0.027), as well as to PTH levels (p < 0.0001). Compared to those with adequate vitamin D stores (>34 ng/ml), those who had consistently low vitamin D stores (18 ng/ml) had a 8% larger gain in bone area (p < 0.05); 11% in BMC (p < 0.05) and no differences in gain in BMD; after adjusting for baseline bone measurements, race, gender, season measured, Tanner stage, and calcium intake. CONCLUSIONS: High normal PTH with low-normal 25(OH)D stores and moderate to high calcium intake may be beneficial to accruing larger bone size and BMC during puberty.

Relationship between patient age and duration of physician visit in ambulatory setting: does one size fit all?

OBJECTIVES: To determine whether patient age, the presence of comorbid illness, and the number of prescribed medications influence the duration of a physician visit in an ambulatory care setting. DESIGN: A cross-sectional study of ambulatory care visits made by adults aged 45 and older to primary care physicians. SETTING: A probability sample of outpatient follow-up visits in the United States using the National Ambulatory Medical Care Survey (NAMCS) 2002 database. PARTICIPANTS: Of 28,738 physician visits in the 2002 NAMCS data set, there were 3,819 visits by adults aged 45 and older included in this study for analysis. MEASUREMENTS: The primary endpoint was the time that a physician spent with a patient at each visit. Covariates included for analyses were patient characteristics, physician characteristics, visit characteristics, and source of payment. Visit characteristics, including the number of diagnoses and the number of prescribed medications, the major diagnoses, and the therapeutic class of prescribed medications, were compared for different age groups (45-64, 65-74, and > or =75) to determine the complexity of the patient's medical conditions. Endpoint estimates were computed by age group and were also estimated based on study covariates using univariate and multivariate linear regression. RESULTS: The mean time+/-standard deviation spent with a physician was 17.9+/-8.5 minutes. There were no differences in the duration of visits between the age groups before or after adjustment for patient covariates. Patients aged 75 and older had more comorbid illness and were prescribed more medications than patients aged 45 to 64 and 65 to 74 (P<.001). Patients aged 75 and older were also prescribed more medications that require specific monitoring and counseling (warfarin, digoxin, angiotensin-converting enzyme inhibitors, diuretics, and levothyroxine) than were patients in other age groups (P<.001). Hypertension, coronary artery disease, atrial fibrillation, congestive heart failure, cerebrovascular disease, and transient ischemic attack were more common in patients aged 75 and older than in other age groups (P<.001). Despite these differences, there were no differences in unadjusted or adjusted duration of physician visit between the age groups. CONCLUSION: Although patients aged 75 and older had more medical conditions and were at higher risk for drug-related problems than younger patients, the duration of physician visits was similar across the age groups. These findings suggest that elderly patients may require a multidisciplinary approach to optimize patient care in the ambulatory setting.