Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. METHODS AND FINDINGS: In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. CONCLUSIONS: Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary

Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.

We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings

Recommendations for Medical Management of Adult Lead Exposure

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 μg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 μg/dL or if two successive blood lead concentrations measured over a 4-week interval are ≥ 20 μg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 μg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 μg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 μg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 μg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application

Abstract Background Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. Methods Participants (ages 25–45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15–30%). Results The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. Conclusions The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use