Drugs and Drug Classes Involved in Overdose Deaths Among Females, United States: 1999-2017.

Background: Drug overdose deaths among U.S. women have risen steadily from 1999 to 2017, especially among certain ages. Various studies report involvement of drugs and drug classes in overdose deaths. Less is known, however, regarding the combinations that are most often indicated on death certificates, particularly among females. Analyzing mutually, exclusive drug/drug class combinations listed on death certificates of females are the objective of this study. Materials and Methods: Mortality data for U.S. female residents were obtained from the 1999 to 2017 National Vital Statistics System (n = 260,782). Analyses included deaths with an underlying cause of death based on International Classification of Diseases, 10th Revision (ICD-10) codes for drug overdoses. The drug/drug class involved included individual 4-digit ICD-10 codes in the range T36.0-T50.9, including poisoning deaths due to all drugs, excluding alcohol. Years from 1999 to 2017 were grouped in six 3-year categories with the most recent year (2017) left separate for analysis. All drug overdose deaths were analyzed in mutually exclusive categories. Results: From 1999 to 2017, the top-listed drug/drug class overall and by year grouping was solely "other and unspecified drugs, medicaments and biological substances"; however, that listing dropped from 25.8% from the 1999 to 2001 period to 14.1% in 2017. Overall, the next most frequent single drug/drug class mentions were "natural and semisynthetic opioids" (20,951; 8.0%) and "cocaine" (10,882; 4.2%). Two of the top five drug/drug class combinations included benzodiazepines ("natural and semisynthetic opioids"/"benzodiazepines" and "methadone"/"benzodiazepines"). Conclusions: Analyzing trends in drugs and drug classes involved in female drug overdose deaths is a critical foundation for developing gender-responsive public health interventions. Reducing high-risk drug use by improving prescribing practices, preventing drug use initiation, and addressing use of multiple drugs can help prevent overdose deaths.

Characteristics and correlates of U.S. clinicians prescribing buprenorphine for opioid use disorder treatment using expanded authorities during the COVID-19 pandemic.

BACKGROUND: To determine how clinicians with a DATA waiver to prescribe buprenorphine for opioid use disorder (OUD) adapted during the COVID-19 pandemic to emergency authorities, including use of telehealth to prescribe buprenorphine, the challenges faced by clinicians, and strategies employed by them to manage patients with OUD. METHODS: From June 23, 2020 to August 19, 2020, we conducted an electronic survey of U.S. DATA-waivered clinicians. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Among 10,238 respondents, 68 % were physicians, 25 % nursing-related providers, and 6% physician assistants; 28 % reported never prescribing or not prescribing in the 12 months prior to the survey. Among the 72 % of clinicians who reported past 12-month buprenorphine prescribing (i.e. active practitioners during the pandemic) 30 % reported their practice setting closed to in-person visits during COVID-19; 33 % reported remote prescribing to new patients without an in-person examination. The strongest predictors of remote buprenorphine prescribing to new patients were prescribing buprenorphine to larger numbers of patients in an average month in the past year and closure of the practice setting during the pandemic; previous experience with remote prescribing to established patients prior to COVID-19 also was a significant predictor. Among clinicians prescribing to new patients without an in-person examination, 5.5 % reported difficulties with buprenorphine induction, most commonly withdrawal symptoms. CONCLUSIONS: Telehealth practices and prescribing to new patients without an in-person examination were adopted by DATA-waivered clinicians during the first six months of COVID-19. Permanent adoption of these authorities may enable expanded access to buprenorphine treatment.

Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Severe illness associated with reported use of synthetic cannabinoids: a public health investigation (Mississippi, 2015).

STUDY OBJECTIVES: In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC. METHODS: A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). RESULTS: Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05). CONCLUSION: SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 µg/g to 152·0 µg/g and MCPG ranged from 44·9 µg/g to 220·0 µg/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention.

Bongkrekic Acid-a Review of a Lesser-Known Mitochondrial Toxin.

INTRODUCTION: Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning. METHODS: We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index ( http://id.portalgaruda.org/ ), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive. CONCLUSIONS: Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.

Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse - New York, 2008-2016.

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Medical Toxicology and Public Health-Update on Research and Activities at the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry : Environmental Exposures among Arctic Populations: The Maternal Organics Monitoring Study in Alaska.

Evidence suggests that in-utero exposure to environmental chemicals, such as persistent organic pollutants (POPs), heavy metals, and radionuclides, that might bioaccumulate in the mother may increase a newborn's risk of adverse developmental, neurological, and immunologic effects. Chemical contamination of bodies of water and strong ocean currents worldwide can drive these chemicals from lower latitudes to Arctic waters where they accumulate in common traditional subsistence foods. In response to concerns of the people from Alaska of the effects of bio-accumulated chemicals on their children, the Maternal Organics Monitoring Study(MOMS) was developed. The objective of the study was to assess the risks and benefits associated with the population's subsistence diet. Data analysis of biological samples at the CDC's NCEH laboratory and maternal questionnaires is ongoing. Results will be provided to Alaska Native communities to help support public health actions and inform future interventions and research.

Exposure Calls to U. S. Poison Centers Involving Electronic Cigarettes and Conventional Cigarettes-September 2010-December 2014.

INTRODUCTION: E-cigarette use is increasing, and the long-term impact on public health is unclear. We described the acute adverse health effects from e-cigarette exposures reported to U.S. poison centers. METHODS: We compared monthly counts and demographic, exposure, and health effects data of calls about e-cigarettes and conventional cigarettes made to poison centers from September 2010 through December 2014. RESULTS: Monthly e-cigarette calls increased from 1 in September 2010, peaked at 401 in April 2014, and declined to 295 in December 2014. Monthly conventional cigarette calls during the same period ranged from 302 to 514. E-cigarette calls were more likely than conventional cigarette calls to report adverse health effects, including vomiting, eye irritation, and nausea. Five e-cigarette calls reported major health effects, such as respiratory failure, and there were two deaths associated with e-cigarette calls. CONCLUSION: E-cigarette calls to U.S. poison centers increased over the study period, and were more likely than conventional cigarettes to report adverse health effects. It is important for health care providers and the public to be aware of potential acute health effects from e-cigarettes. Developing strategies to monitor and prevent poisonings from these novel devices is critical.

Long-term renal and neurologic outcomes among survivors of diethylene glycol poisoning.

IMPORTANCE: At least 13 medication-associated diethylene glycol (DEG) mass poisonings have occurred since 1937. To our knowledge, this is the first longitudinal study characterizing long-term health outcomes among survivors beyond the acute poisoning period. OBJECTIVE: To characterize renal and neurologic outcomes among survivors of a 2006 DEG mass-poisoning event in Panama for 2 years after exposure. DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal study used descriptive statistics and mixed-effects repeated-measures analysis to evaluate DEG-poisoned survivors at 4 consecutive 6-month intervals (0, 6, 12, and 18 months). Case patients included outbreak survivors with a history of (1) ingestion of DEG-contaminated medication, (2) hospitalization for DEG poisoning, and (3) an unexplained serum creatinine level of 1.5 mg/dL or higher (to convert to micromoles per liter, multiply by 88.4) during acute illness or unexplained exacerbation of preexisting end-stage renal disease. MAIN OUTCOMES AND MEASURES: Demographics, mortality, dialysis dependence, renal function, neurologic signs and symptoms, and nerve conduction studies. RESULTS: Of the 32 patients enrolled, 5 (15.6%) died and 1 was lost to follow-up, leaving 26 patients at 18 months. Three (9.4%) missed 1 or more evaluations. The median age was 62 years (range, 15-88 years), and 59.4% were female. Three (9.4%) patients had preexisting renal failure. Enrollment evaluations occurred at a median of 108 days (range, 65-154 days) after acute illness. The median serum creatinine level for the 22 patients who were not dialysis dependent at time 0 was 5.9 mg/dL (range, 1.8-17.1 mg/dL) during acute illness and 1.8 mg/dL (range, 0.9-5.9 mg/dL) at time 0. Among non-dialysis-dependent patients, there were no significant differences in the log of serum creatinine or estimated glomerular filtration rate over time. The number of patients with subjective generalized weakness declined significantly over time (P < .001). A similar finding was observed for any sensory loss (P = .05). The most common deficits at enrollment were bilateral lower extremity numbness in 13 patients (40.6%) and peripheral facial nerve motor deficits in 7 (21.9%). All patients with neurologic deficits at enrollment demonstrated improvement in motor function over time. Among 28 patients (90.3%) with abnormal nerve conduction study findings at enrollment, 10 (35.7%) had motor axonal involvement, the most common primary abnormality. CONCLUSIONS AND RELEVANCE: Neurologic findings of survivors tended to improve over time. Renal function generally improved among non-dialysis-dependent patients between acute illness and the first evaluation with little variability thereafter. No evidence of delayed-onset neurologic or renal disease was observed.

Notes from the field: calls to poison centers for exposures to electronic cigarettes--United States, September 2010-February 2014.

Electronic nicotine delivery devices such as electronic cigarettes (e-cigarettes) are battery-powered devices that deliver nicotine, flavorings (e.g., fruit, mint, and chocolate), and other chemicals via an inhaled aerosol. E-cigarettes that are marketed without a therapeutic claim by the product manufacturer are currently not regulated by the Food and Drug Administration (FDA). In many states, there are no restrictions on the sale of e-cigarettes to minors. Although e-cigarette use is increasing among U.S. adolescents and adults, its overall impact on public health remains unclear. One area of concern is the potential of e-cigarettes to cause acute nicotine toxicity. To assess the frequency of exposures to e-cigarettes and characterize the reported adverse health effects associated with e-cigarettes, CDC analyzed data on calls to U.S. poison centers (PCs) about human exposures to e-cigarettes (exposure calls) for the period September 2010 (when new, unique codes were added specifically for capturing e-cigarette calls) through February 2014. To provide a comparison to a conventional product with known toxicity, the number and characteristics of e-cigarette exposure calls were compared with those of conventional tobacco cigarette exposure calls.

Clinical, laboratory, diagnostic, and histopathologic features of diethylene glycol poisoning--Panama, 2006.

STUDY OBJECTIVE: Diethylene glycol is a toxic industrial solvent responsible for more than 13 mass poisonings since 1937. Little is known about the clinical spectrum, progression, and neurotoxic potential of diethylene glycol-associated disease because of its high mortality and the absence of detailed information in published mass poisoning reports. This incident includes the largest proportion of cases with neurotoxic signs and symptoms. We characterize the features of a diethylene glycol mass poisoning resulting from a contaminated cough syrup distributed in Panama during 2006. METHODS: This was a retrospective chart review and descriptive analysis in a tertiary level, urban health care facility. A case was a person admitted to the Social Security Metropolitan Hospital in Panama City between June 1 and October 22, 2006, with unexplained acute kidney injury and a serum creatinine level of greater than or equal to 2 mg/dL, or unexplained chronic renal failure exacerbation (>2-fold increase in baseline serum creatinine level) and history of implicated cough syrup exposure. Main outcomes and measures were demographic, clinical, laboratory, diagnostic, histopathologic, and mortality data with descriptive statistics. RESULTS: Forty-six patients met inclusion criteria. Twenty-four (52%) were female patients; median age was 67 years (range 25 to 91 years). Patients were admitted with acute kidney injury or a chronic renal failure exacerbation (median serum creatinine level 10.0 mg/dL) a median of 5 days after symptom onset. Forty patients (87%; 95% confidence interval [CI] 74% to 95%) had neurologic signs, including limb (n=31; 77%; 95% CI 62% to 89%) or facial motor weakness (n=27; 68%; 95% CI 51% to 81%). Electrodiagnostics in 21 patients with objective weakness demonstrated a severe sensorimotor peripheral neuropathy (n=19; 90%; 95% CI 70% to 99%). In 14 patients without initial neurologic findings, elevated cerebrospinal fluid protein concentrations without pleocytosis were observed: almost all developed overt neurologic illness (n=13; 93%; 95% CI 66% to 100%). Despite use of intensive care and hemodialysis therapies, 27 (59%) died a median of 19 days (range 2 to 50 days) after presentation. CONCLUSION: A high proportion of patients with diethylene glycol poisoning developed progressive neurologic signs and symptoms in addition to acute kidney injury. Facial or limb weakness with unexplained acute kidney injury should prompt clinicians to consider diethylene glycol poisoning. Elevated cerebrospinal fluid protein concentrations without pleocytosis among diethylene glycol-exposed persons with acute kidney injury may be a predictor for progressive neurologic illness.

Passive multistate surveillance for neutropenia after use of cocaine or heroin possibly contaminated with levamisole.

STUDY OBJECTIVE: To characterize the demographic, clinical, and epidemiologic features of levamisole-associated neutropenia in cocaine or heroin users. METHODS: State health departments were recruited for participation when the Centers for Disease Control and Prevention (CDC) was notified of potential cases by a clinician, a health department official, or a poison center between October 15, 2009, and May 31, 2010. A case was defined as a person with an absolute neutrophil count less than 1,000 cells/µL (or a WBC count <2,000 cells/µL) and a self-reported history or laboratory confirmation of cocaine or heroin use. Health department officials abstracted data from medical charts, attempted a patient interview, and submitted data to CDC for descriptive analysis. RESULTS: Of the 46 potential cases reported from 6 states, half met eligibility criteria and had medical chart abstractions completed (n=23; 50%). Of these, close to half of the patients were interviewed (n=10; 43%). The average age was 44.4 years; just over half were men (n=12; 52%). The majority of patients presented to emergency departments (n=19; 83%). More than half presented with infectious illnesses (n=12; 52%), and nearly half reported active skin lesions (n=10; 44%). The majority of interview respondents used cocaine greater than 2 to 3 times a week (n=9; 90%), used cocaine more than 2 years (n=6; 60%), and preferred crack cocaine (n=6; 60%). All were unaware of exposure to levamisole through cocaine and of levamisole's inherent toxicity (n=10; 100%). CONCLUSION: Physicians should suspect levamisole exposure in patients using illicit drugs, cocaine in particular, who present with unexplained neutropenia. Most patients reported chronic cocaine use and were unaware of levamisole exposure. Cocaine use is more prevalent among men; however, our results identified a higher-than-expected proportion of female users with neutropenia, suggesting women may be at higher risk. Emergency physicians and practitioners are uniquely positioned to recognize these patients early during their hospital course, elucidate a history of cocaine or other drug exposure, and optimize the likelihood of confirming exposure by arranging for appropriate drug testing.

Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

BACKGROUND: During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. METHODS: Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. RESULTS: Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 µg/ml (n = 91, range <0.002-0.051 µg/ml) and 0.02 µg/ml (n = 32, range <0.004-0.069 µg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %). CONCLUSION: Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Consumption of pesticide-treated wheat seed by a rural population in Malawi.

An outbreak of typhoid fever in rural Malawi triggered an investigation by the Malawi Ministry of Health and the Centers for Disease Control and Prevention in July 2009. During the investigation, villagers were directly consuming washed, donated, pesticide-treated wheat seed meant for planting. The objective of this study was to evaluate the potential for pesticide exposure and health risk in the outbreak community. A sample of unwashed (1430 g) and washed (759 g) wheat seed donated for planting, but which would have been directly consumed, was tested for 365 pesticides. Results were compared with each other (percentage change), the US Environmental Protection Agency's (EPA) health guidance values and estimated daily exposures were compared with their Reference dose (RfD). Unwashed and washed seed samples contained, respectively: carboxin, 244 and 57 p.p.m.; pirimiphos methyl, 8.18 and 8.56 p.p.m.; total permethrin, 3.62 and 3.27 p.p.m.; and carbaryl, 0.057 and 0.025 p.p.m.. Percentage change calculations (unwashed to washed) were as follows: carboxin, -76.6%; pirimiphos methyl, +4.6%; total permethrin, -9.7%; and carbaryl -56.1%. Only carboxin and total permethrin concentration among washed seed samples exceeded US EPA health guidance values (285 × and seven times, respectively). Adult estimated exposure scenarios (1 kg seed) exceeded the RfD for carboxin (8 × ) and pirimiphos methyl (12 × ). Adult villagers weighing 70 kg would have to consume 0.123, 0.082, 1.06, and 280 kg of washed seed daily to exceed the RfD for carboxin, pirimiphos methyl, permethrins, and carbaryl, respectively. Carboxin, pirimiphos methyl, permethrins, and carbaryl were detected in both unwashed and washed samples of seed. Carboxin, total permethrin, and carbaryl concentration were partially reduced by washing. Health risks from chronic exposure to carboxin and pirimiphos methyl in these amounts are unclear. The extent of this practice among food insecure communities receiving relief seeds and resultant health impact needs further study.

Mercury exposure among artisanal gold miners in Madre de Dios, Peru: a cross-sectional study.

INTRODUCTION: Exposure to mercury, a toxic metal, occurs primarily from inhaling mercury vapors or consuming methylmercury-contaminated fish. One third of all anthropogenic mercury emissions worldwide are from artisanal gold mining, which uses mercury to extract gold. Although recent reports suggest that the Madre de Dios region in Peru (with >30,000 artisanal miners) has extensive mercury contamination, residents had never been assessed for mercury exposure. Thus, our objective was to quantify mercury exposure among residents of an artisanal mining town in Madre de Dios and to assess risk factors for exposure. METHODS: We conducted a cross-sectional assessment of 103 residents of an artisanal gold mining town in July 2010. Each participant provided a urine and blood sample and completed a questionnaire assessing potential exposures and health outcomes. We calculated geometric mean (GM) urine total mercury and blood methylmercury concentrations and compared log-transformed concentrations between subgroups using linear regression. RESULTS: One third (34.0 %) of participants were gold miners. All participants had detectable urine total mercury (GM, 5.5 µg/g creatinine; range, 0.7-151 µg/g creatinine) and 91 % had detectable blood methylmercury (GM, 2.7 µg/L; range, 0.6-10 µg/L); 13 participants (13 %) reported having kidney dysfunction or a neurological disorder. Urine total mercury concentrations were higher among people who heated gold-mercury amalgams compared with people who never heated amalgams (p < 0.05); methylmercury concentrations were higher among fish consumers compared with nonfish consumers (p < 0.05). CONCLUSION: Our findings suggest that mercury exposure may be widespread in Huaypetue.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

BACKGROUND: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. METHODS: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). RESULTS: We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. CONCLUSIONS: The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Characterization of Animal Exposure Calls Captured by the National Poison Data System, 2000-2010.

OBJECTIVE: Our objective was to characterize the data captured in all animal exposure calls reported to the National Poison Data System (NPDS), a national poison center reporting database, from 1 January 2000 through 31 December 2010 and identify Poison Center usage and needs in animal exposure calls. DESIGN: We calculated descriptive statistics characterizing animal type, exposure substance, medical outcome, year and month of call, caller location, and specific state for all animal exposure call data in NPDS from 1 January 2000 to 31 December 2010. SAS version 9.2 was used for the analysis. RESULTS: There were 1,371,095 animal exposure calls out of 28,925,496 (4.7%) total human and animal exposure calls in NPDS during the study period. The majority involved companion animal exposures with 88.0% canine exposures and 10.4% feline exposures. Pesticides were the most common exposure substance (n=360,375; 26.3%), followed by prescription drugs (n=261,543; 18.6%). The most common outcome reported was 'Not followed, judged as nontoxic exposure or minimal clinical effects possible' (n=803,491; 58.6%), followed by 'Not followed, judged potentially toxic exposure' (n=263,153; 19.2%). There were 5,388 deaths reported. Pesticide exposures were responsible for the greatest number of deaths (n=1,643; 30.4%). CONCLUSIONS AND CLINICAL RELEVANCE: Approximately 1 in 20 calls to PCs are regarding potentially toxic exposures to animals, suggesting a need for veterinary expertise and resources at PCs. Pesticides are one of the greatest toxic exposure threats to animals, both in numbers of exposures and severity of clinical outcomes, and is an important area for education, prevention, and treatment.

Organizational and command aspects for coordinating the public health response to an outbreak of acute renal failure, Republic of Panama, 2006.

The Ministry of Health of Panama (MINSA) received several reports of ill persons who had clinical presentations of acute renal insufficiency or failure during September and October 2006. On 01 October 2006, the MINSA formally asked the Pan-American Health Organization (PAHO) and the US Centers for Disease Control and Prevention (CDC) to assist with the investigation. Additional agencies involved in the response included the US Food and Drug Administration (FDA), the Gorgas Institute for Health Studies (GIHS), and the Social Security Health System (SSHS) of Panama. Through a joint effort, the MINSA, CDC, FDA, GIHS, SSHS, and PAHO were able to characterize the illness, identify the etiological agent, identify the population-at-risk, and launch an unprecedented media and social mobilization effort to prevent additional cases.International outbreak responses may require familiarity with basic emergency management principles beyond technical or scientific considerations. The management, logistical capabilities, team interaction, and efficiency of outbreak investigations can be enhanced substantially by having staff already familiar with common operational frameworks for incident responses. This report describes the inter-agency coordination and organizational structure implemented during an international response to identify the cause of an outbreak of acute renal failure in Panama.