Blood Lead Levels in Females of Childbearing Age in Flint, Michigan, and the Water Crisis.

OBJECTIVE: To compare blood lead levels in females of childbearing age, 12-50 years, living within and adjacent to Flint, Michigan, before, during, and after the Flint River water exposure and compare the levels to those that have been shown to cause fetal loss and preterm birth. METHODS: The switch in the community water source to the Flint River occurred on April 25, 2014, and was reverted to the original source on October 15, 2015. Using a retrospective cross-sectional study design using geocoded blood lead levels obtained from all females of childbearing age available from a single hospital database, we compared blood lead levels for the following 18-month time periods: April 25, 2012-October 15, 2013 (PRE), April 25, 2014-October 15, 2015 (DURING), and April 25, 2016-October 15, 2017 (POST). RESULTS: Results are reported as geometric mean (95% CI). Within Flint, PRE blood lead levels in females of childbearing age were 0.69 micrograms/dL (95% CI 0.63-0.75), DURING blood lead levels were 0.65 micrograms/dL (95% CI 0.60-0.71), and POST blood lead levels were 0.55 micrograms/dL (95% CI 0.54-0.56). DURING Flint River water exposure blood lead levels were not significantly different than the PRE Flint River water time period. POST Flint River water exposure blood lead levels were significantly lower than both PRE and DURING levels. Overall, lower blood lead levels were found outside the Flint boundary in all cohorts. CONCLUSION: Blood lead levels in Flint females of childbearing age did not increase during the Flint River water exposure and subsequent 18-month time period. Mean blood lead levels during the Flint River water exposure are not consistent with the markedly higher blood lead levels reported in the literature to be associated with fetal loss, low birth weight, or preterm birth.

Analysis of blood lead levels of young children in Flint, Michigan before and during the 18-month switch to Flint River water.

Background: The toxicity of lead, like any xenobiotic, is directly linked to the duration of exposure and toxin concentration in the body. The elevation in blood lead levels (BLLs) in young Flint, Michigan children noted in time-periods before, and during the 18-month exposure to Flint River water (FRW) from 25 April 2014 to 15 October 2015 is well-known internationally. The length of time BLLs were elevated is unknown, yet key in understanding the potential health impact of the event. The objective of this study was to evaluate whether BLLs in Flint children were increased during the entire 18-month FRW exposure compared to similar earlier time periods. Methods: We conducted a retrospective study analyzing BLLs from Flint children aged 5 years and under. The geometric mean (GM) BLLs and percentages of BLLs ≥5.0 µg/dL in Period I: 25 April 2006 to 15 October 2007 (earliest timeframe available for study) and Period II: 25 April 2012 to 15 October 2013 (timeframe immediately before the water switch), were compared to Period III, 25 April 2014 to 15 October 2015 (FRW exposure). Results: There were 5663 BLLs available for study. GM ± SE BLLs decreased from 2.19 ± 0.03 µg/dL in Period I to 1.47 ± 0.02 µg/dL in Period II [95% CI, 0.64, 0.79]; p<.001 and decreased further to 1.32 ± 0.02 µg/dL during the FRW Period III [95% CI, 0.79, 0.95]; p<.001. The percentage of BLLs ≥5.0 µg/dL decreased from Period I (10.6%) to Period II (3.3%) [95% CI, 5.7, 8.8]; p<.001 and from Period I to Period III (3.9%) [95% CI, 5.0, 8.2]; p=.002. The 0.6% increase from Period II to Period III was not statistically significant [95% CI, -1.9, 0.57]; p=.30. Conclusion: Analyses of GM and percentages ≥5.0 µg/dL of BLLs do not support the occurrence of a global increase in BLLs in young children of Flint during the entire 18-month period of FRW exposure.

Blood Lead Levels of Children in Flint, Michigan: 2006-2016.

OBJECTIVE: We evaluated the increases in blood lead levels (BLLs) observed in young children in Flint, Michigan, during their exposure to corrosive Flint River water during the years 2014 and 2015 and compared their BLLs to those of Flint children measured during the years 2006-2013 and 2016. STUDY DESIGN: This was a retrospective study design using BLLs extracted from databases from 2006 to 2016. We analyzed a population sample of 15 817 BLLs from children aged ≤5 years with potential exposure to contaminated Flint River water. Percentages of BLLs ≥5.0 µg/dL and geometric mean (GM) BLLs were analyzed over time. RESULTS: A significant decline in the percentages of BLLs ≥5.0 µg/dL from 11.8% in 2006 to 3.2% in 2016 was observed (P < .001). GM ± SE BLLs decreased from 2.33 ± 0.04 µg/dL in 2006 to 1.15 ± 0.02 µg/dL in 2016 (P < .001). GM BLLs increased twice: from 1.75 ± 0.03 µg/dL to 1.87 ± 0.03 µg/dL (2010-2011) and from 1.19 ± 0.02 µg/dL to 1.30 ± 0.02 µg/dL (2014-2015). Overall, from 2006 to 2016, there was a 72.9% decrease in the percentage of children with BLLs ≥5.0 µg/dL and a 50.6% decrease in GM BLLs. CONCLUSION: These findings suggest that the 11 year trend of annual decreases in BLLs in children in Flint, Michigan, reversed to a degree consistent with random variation from 2010 to 2011, and again during the exposure to Flint River water in 2014-2015. Historically, public health efforts to reduce BLLs of young children in Flint have been effective over the 11-year period studied.

Blood Lead Concentrations of Children in the United States: A Comparison of States Using Two Very Large Databases.

OBJECTIVES: To determine whether there are substantial differences by state between 2 large datasets in the proportion of children with elevated blood lead levels (BLLs); to identify states in which the percentage of elevated BLLs is high in either or both datasets; and to compare the percentage of elevated BLLs in individual states with those of children living in Flint, Michigan, during the months when these children were exposed to lead-contaminated drinking water. STUDY DESIGN: Tables of BLLs for individual states from the Quest Diagnostics and the Centers for Disease Control and Prevention datasets for 2014-2015, containing more than 3 million BLLs of young children?

Mad honey sex: therapeutic misadventures from an ancient biological weapon.

STUDY OBJECTIVE: "Mad honey" poisoning occurs from ingestion of honey produced from grayanotoxin-containing nectar, often in the setting of use as an alternative medicine. This study is designed to assess the clinical effects, demographics, and rationale behind self-induced mad honey poisoning. METHODS: The study consisted of 2 components: a standardized chart review of the signs, symptoms, and treatment of patients with mad honey ingestion, treated in our emergency department between December 2002 and January 2008; and a cross-sectional survey of a convenience sample of beekeepers specializing in the production and distribution of mad honey. RESULTS: We identified 21 cases. Patients were overwhelmingly men (18/21) and older (mean [SD]), 55 [11] years. Local beekeepers (N=10) ranked sexual performance enhancement as the most common reason for therapeutic mad honey consumption in men aged 41 through 60 years. Symptoms began 1.0 hour (SD 0.6 hour) after ingestion and included dizziness, nausea, vomiting, and syncope. Abnormal vital signs included hypotension (mean arterial pressure 58 mm Hg [SD 13 mm Hg]) and bradycardia (mean 45 beats/min [SD 9 beats/min]). Seventeen patients had sinus bradycardia and 2 had junctional rhythm. Nine patients were treated with atropine; 1 patient received dopamine. All patients were discharged 18 to 48 hours after admission. CONCLUSION: A dietary and travel history should be included in the assessment of middle-aged men presenting with bradycardia and hypotension. A mad honey therapeutic misadventure may be the cause rather than a primary cardiac, neurologic, or metabolic disorder.

Diagnosis of loxoscelism in two Turkish patients confirmed with an enzyme-linked immunosorbent assay (ELISA) and non-invasive tissue sampling.

Confirmed envenomations due to Loxosceles reclusa have not been previously documented in Turkey, to our knowledge. This brief report describes two Turkish patients with suspected envenomation by Loxosceles spider bites on the eyelids. Material obtained by swabbing the lesions with gauze was tested using a venom-specific enzyme-linked immunosorbent assay (ELISA). Both patients tested positive for the presence of Loxosceles venom.

Diagnosis of loxoscelism in a child confirmed with an enzyme-linked immunosorbent assay and noninvasive tissue sampling.

BACKGROUND: Confirmation of mild bites caused by Loxosceles reclusa with swab testing has not been previously documented, to our knowledge. METHODS: We report a case using an enzyme-linked immunosorbent assay (ELISA) test. RESULTS: A lesion lacking necrosis or other specific signs of loxoscelism was confirmed by identification of the Loxosceles venom and further confirmed by identification of a spider found in the patient's bed. LIMITATIONS: This is a pilot single-case report for this enzyme-linked immunosorbent assay test. CONCLUSIONS: A sensitive and specific enzyme-linked immunosorbent assay designed to detect Loxosceles venom, using a specimen obtained by swabbing the lesion, can aid in diagnosis of loxoscelism.

Detection of Loxosceles species venom in dermal lesions: a comparison of 4 venom recovery methods.

STUDY OBJECTIVE: Loxosceles species spider envenomations may produce necrotic, disfiguring dermal inflammatory lesions resembling neutrophilic dermatoses. With definitive treatment options lacking, clinicians are reluctant to obtain invasive biopsy specimens for diagnostic analysis. We compared less invasive venom collection methods and determined the time limit after inoculation for feasible venom recovery in an animal model. METHODS: Nine New Zealand rabbits were randomized to 1 of 3 groups (n=3). Groups 1 and 2 were inoculated intradermally with 3 microg of L reclusa venom at 5 inoculation sites per rabbit. Albumin (3 microg) was injected intradermally in each rabbit as a negative control. Hair (group 1) and aspirate samples (group 2) were collected (1 time per site) over a 1-week period after inoculation. Group 3 was inoculated with 3 microg of Loxosceles species venom on 1 flank and 3 microg of albumin on the opposite flank. Daily serum specimens were collected over a 7-day period. On day 7, dermal punch biopsy specimens were taken from the venom and control inoculation sites. Hair, aspirate, biopsy, and serum specimens were assayed for venom by using an enzyme-linked immunosorbent assay. A generalized linear model was fit with the generalized estimating equation method to estimate the mean differences between groups. RESULTS: Venom was detected in hair, aspirate, and biopsy specimens on all days of the study period. Hair samples yielded venom recovery on day 1 (median 0.062 ng/100 microL; mean difference 0.054 ng/100 microL; 95% confidence interval [CI] 0.048 to 0.059) through day 7 (median 0.020 ng/100 microL; mean difference 0.020 ng/100 microL; 95% CI 0.013 to 0.027). Aspirates were positive for venom recovery on day 1 (median 0.275 ng/100 microL; mean difference 0.231 ng/100 microL; 95% CI 0.192 to 0.271) through day 7 (median 0.0 ng/100 microL; mean difference 0.032 ng/100 microL; 95% CI -0.18 to 0.078). The highest venom yield was from the biopsy specimens (median 1.75 ng/100 microL; mean difference 0.041 ng/100 microL; 95% CI 0.033 to 0.027). Venom was undetectable in all serum samples. CONCLUSION: Loxosceles species venom is detectable in hair, aspirate, and dermal biopsy specimens at least 7 days after venom inoculation and undetectable in serum by using the rabbit model.

A new assay for the detection of Loxosceles species (brown recluse) spider venom.

STUDY OBJECTIVE: Dermal lesions from unrelated arthropod species and medical causes appear similar to Loxosceles species (brown recluse spider) bites. This may result in delayed diagnosis and treatment. We developed a sensitive Loxosceles species venom enzyme-linked immunosorbent assay (ELISA) and characterized the specificity of the assay by evaluating antigenic cross-reactivity from a variety of North American arthropod venoms. METHODS: North American arthropod (14 spiders, 2 scorpions, and 1 bee) venoms were studied. Three venom amounts (diluted in 100 microL of ELISA buffer) were assayed: 16,000 ng, 2,000 ng, and 40 ng. The latter quantity was selected because this is the observed maximum amount of venom we detect when inoculating dermis with amounts likely to be deposited by a spider bite. The larger venom amounts are overwhelming quantities designed to test the limits of the assay for arthropod venom cross-reactivity. Similar amounts of Loxosceles species venom and bovine albumin served as positive and negative controls, respectively. RESULTS: At the lowest amount of venom tested (40 ng), the ELISA detected only the Loxosceles species positive control. When 2,000 ng was assayed, only Scytodes fusca and Kukulcania hibernalis arachnid venoms (in addition to Loxosceles species) cross-reacted to the assay. Finally, at 16,000 ng, the ELISA assay modestly detected Diguetia canities, Heteropoda venatoria, Tegenaria agrestis, Plectreurys tristes, Dolomedes tenebrosus, and Hadrurus arizonensis arachnid venoms. CONCLUSION: Cross-reactivity was observed in 8 of 17 North American arthropod venoms when large venom amounts were assayed with a Loxosceles species ELISA. By using a relevant quantity of venom, 40 ng, the assay was specific for Loxosceles species venom. The venom specificity of the ELISA may allow clinical application in Loxosceles species endemic regions of North America.

Calcium and beta receptor antagonist overdose: a review and update of pharmacological principles and management.

Calcium channel and beta-adrenergic receptor antagonists are common pharmaceutical agents with multiple overlapping clinical indications. When used appropriately, these agents are safe and efficacious. In overdose, however, these agents have the potential for serious morbidity. Calcium channel blockers and beta blockers share similar physiological effects on the cardiovascular system, such as hypotension and bradycardia, in overdose and occasionally at therapeutic doses. The initial management for symptomatic overdose of both drug classes consists of supportive care measures. Other therapies including administration of glucagon, calcium, catecholamines, phosphodiesterase inhibitors and insulin have been used with varying degrees of success. In addition, intra-aortic balloon pump and extracorporeal membrane oxygenation techniques have been successfully utilized in refractory cases. This article reviews beta blocker and calcium channel blocker pharmacological principles and updates current management strategies.