Reductions in spice lead levels in the republic of Georgia: 2020-2022.

Spice adulteration using yellow lead chromate-based pigments has been documented as a growing global health concern. Spices from the Republic of Georgia with extremely high levels of lead, up to an order of magnitude higher than any other spices worldwide, have been implicated as sources of child lead poisoning. The objectives of this study were to 1) evaluate lead concentrations in spices sampled across the country of Georgia between 2020 and 2022, and 2) assess factors associated with spice adulteration, specifically the role of spice quality and regulatory enforcement. Spice samples were collected from 29 cities nationwide. The most populous cities were selected in each administrative region as well as those of importance to the spice supply chain. Sampling was carried out at the largest spice bazaars in each city. The regions of Adjara and Imereti were the focus of qualitative interviews conducted in 2021 with key businesspeople selling spices with very high and low levels of lead. The same cities and bazaars were visited at each of three sampling periods between 2020 and 2022. In total, 765 spice samples were collected. Lead concentrations in spices decreased over time, with a maximum of 14,233 µg/g in 2020 down to 36 µg/g in the final sampling round of 2022. A logistic regression determined that sampling round, region and spice type were associated with elevated lead in samples. Samples from Adjara and those containing marigold had the highest lead levels. Interviews with eighteen prominent spice vendors revealed difficulties sourcing sufficient quantities of high quality, brightly colored marigold, and concerns about adulteration. Interviews with two authorities from the National Food Authority highlighted the increased attention on regulating lead in spices since 2018. Continued monitoring and periodic regulatory enforcement may adequately disincentivize further adulteration with lead chromate in the spice industry in Georgia.

Substance use during hospitalisation requiring an urgent clinical response: an opportunity for intervention.

BACKGROUND: There are few reports on drug use in patients while hospitalised and none regarding management or clinical outcomes. AIMS: To describe cases of drug use by inpatients requiring an urgent clinical response. METHODS: We retrospectively reviewed cases at a teaching hospital in Sydney, Australia, from February 2019 to March 2021. RESULTS: Thirty cases were identified, with no deaths. Two patient groups were identified: (i) substance use disorders, using illicit drugs and (ii) self-harm history, using prescribed or over-the-counter drugs. Management involved cardiac monitoring (40%), intensive care (30%), charcoal (20%), antidotes (20%) and intubation (13%). Discharge was planned in 22 of 30 patients, against medical advice in four and directed by medical staff in four. CONCLUSIONS: Inpatient drug use requiring an urgent clinical response was infrequently recognised but presents a risk of harm to patients and staff and increases service utilisation and costs. Both harm reduction and systematic approaches guided by institutional policy are recommended. Using these events as reachable moments to address driving factors may modify patients' risk from future events.

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.

Child lead exposure near abandoned lead acid battery recycling sites in a residential community in Bangladesh: Risk factors and the impact of soil remediation on blood lead levels.

Lead is a potent neurotoxin that is particularly detrimental to children's cognitive development. Batteries account for at least 80% of global lead use and unsafe battery recycling is a major contributor to childhood lead poisoning. Our objectives were to assess the intensity and nature of child lead exposure at abandoned, informal used lead acid battery (ULAB) recycling sites in Kathgora, Savar, Bangladesh, as well as to assess the feasibility and effectiveness of a soil remediation effort to reduce exposure. ULAB recycling operations were abandoned in 2016 due to complaints from residents, but the lead contamination remained in the soil after operations ceased. We measured soil and blood lead levels (BLLs) among 69 children living within 200 m of the ULAB recycling site once before, and twice after (7 and 14 months after), a multi-part remediation intervention involving soil capping, household cleaning, and awareness-raising activities. Due to attrition, the sample size of children decreased from 69 to 47 children at the 7-month post-intervention assessment and further to 25 children at 14 months. We conducted non-parametric tests to assess changes in soil lead levels and BLLs. We conducted baseline surveys, as well as semi-structured interviews and observations with residents throughout the study period to characterize exposure behaviors and the community perceptions. We conducted bivariate and multivariate regression analyses of exposure characteristics to determine the strongest predictors of baseline child BLLs. Prior to remediation, median soil lead concentrations were 1400 mg/kg, with a maximum of 119,000 mg/kg and dropped to a median of 55 mg/kg after remediation (p < 0.0001). Among the 47 children with both baseline and post-intervention time 1 measurements, BLLs dropped from a median of 21.3 µg/dL to 17.0 µg/dL at 7 months (p < 0.0001). Among the 25 children with all three measurements, BLLs dropped from a median of 22.6 µg/dL to 14.8 µg/dL after 14 months (p < 0.0001). At baseline, distance from a child's residence to the nearest abandoned ULAB site was the strongest predictor of BLLs and baseline BLLs were 31% higher for children living within 50 m from the sites compared to those living further away (n = 69, p = 0.028). Women and children spent time in the contaminated site daily and relied on it for their livelihoods and for recreation. Overall, this study highlights the intensity of lead exposure associated with the ULAB recycling industry. Additionally, we document the feasibility and effectiveness of a multi-part remediation intervention at a contaminated site embedded within a residential community; substantially reducing child BLLs and soil lead concentrations.

Paraneoplastic gastrointestinal dysmotility due to non-Hodgkin diffuse large B cell lymphoma: a case report.

Paraneoplastic gastrointestinal dysmotility is a rare entity which occurs in association with malignancy. We present the second case associated with lymphoma, characterised by generalised gastrointestinal dysmotility with constipation, malnutrition, weight loss, and capsule endoscope retention. This case highlights the importance of maintaining a high index of suspicion for malignancy in patients with unexplained gastrointestinal dysmotility.

Evidence of turmeric adulteration with lead chromate across South Asia.

Food adulteration with toxic chemicals is a global public health threat. Lead chromate adulterated spices have been linked with lead poisoning in many countries, from Bangladesh to the United States. This study systematically assessed lead chromate adulteration in turmeric, a spice that is consumed daily across South Asia. Our study focused on four understudied countries that produce >80 % of the world's turmeric and collectively include 1.7 billion people, 22 % of the world's population. Turmeric samples were collected from wholesale and retail bazaars from 23 major cities across India, Pakistan, Sri Lanka, and Nepal between December 2020 and March 2021. Turmeric samples were analyzed for lead and chromium concentrations and maximum child blood lead levels were modeled in regions where samples had detectable lead. A total of 356 turmeric samples were collected, including 180 samples of dried turmeric roots and 176 samples of turmeric powder. In total, 14 % of the samples (n = 51) had detectable lead above 2 µg/g. Turmeric samples with lead levels greater than or equal to 18 µg/g had molar ratios of lead to chromium near 1:1, suggestive of lead chromate adulteration. Turmeric lead levels exceeded 1000 µg/g in Patna (Bihar, India) as well as Karachi and Peshawar (Pakistan), resulting in projected child blood lead levels up to 10 times higher than the CDC's threshold of concern. Given the overwhelmingly elevated lead levels in turmeric from these locations, urgent action is needed to halt the practice of lead chromate addition in the turmeric supply chain.

Rapid Market Screening to assess lead concentrations in consumer products across 25 low- and middle-income countries.

Lead exposure can have serious consequences for health and development. The neurological and behavioral effects of lead are considered irreversible. Young children are particularly vulnerable to lead poisoning. In 2020, Pure Earth and UNICEF estimated that one in three children had elevated blood lead levels above 5 µg/dL. The sources of lead exposure vary around the world and can range from household products, such as spices or foodware, to environmental pollution from nearby industries. The aim of this study was to analyze common products from markets in low- and middle-income countries (LMICs) for their lead content to determine whether they are plausible sources of exposure. In 25 LMICs, the research teams systematically collected consumer products (metal foodware, ceramics, cosmetics, paints, toys, spices and other foods). The items were analyzed on site for detectable lead above 2 ppm using an X-ray fluorescence analyzer. For quality control purposes, a subset of the samples was analyzed in the USA using inductively coupled plasma mass spectrometry. The lead concentrations of the individual product types were compared with established regulatory thresholds. Out of 5007 analyzed products, threshold values (TV) were surpassed in 51% for metal foodware (TV 100 ppm), 45% for ceramics (TV 100 ppm), and 41% for paints (TV 90 ppm). Sources of exposure in LMICs can be diverse, and consumers in LMICs lack adequate protection from preventable sources of lead exposure. Rapid Market Screening is an innovative, simple, and useful tool to identify risky products that could be sources of lead exposure.

Drug-induced liver injury from selective androgen receptor modulators, anabolic-androgenic steroids and bodybuilding supplements in Australia.

BACKGROUND: Reports of DILI due to herbal and dietary supplements have been increasing over time. AIMS: To characterise clinical, laboratory and histopathological phenotypes and outcomes of drug-induced liver injury (DILI) due to anabolic-androgenic steroids (AAS), selective androgen receptor modulators (SARMs), and bodybuilding supplements (BBS) in Australia. METHODS: Retrospective case series. Patients presented to nine Australian tertiary hospitals, 2017-2023. DILI was defined biochemically and patients were included if their treating physician attributed DILI to preceding use of AAS, SARMs or BBS. Primary endpoint was time to normalisation of liver biochemistry. Secondary endpoints were hospitalisation for investigation or management of DILI, death attributable to liver injury, and liver transplantation. RESULTS: Twenty-three cases of DILI were identified, involving 40 drugs: 18 AAS, 14 SARMs and eight BBS. Patients were predominantly male (22/23), with median age 30 years (IQR 26-42). Most were symptomatic (21/23). Median latency of onset was 58 days (IQR 28-112 days) from drug commencement. Most patients (17/23) were admitted to hospital. Based on updated Roussel Uclaf Causality Assessment Method, DILI was possible in 17/23, probable in 2/23 and unlikely in 4/23. Median time to normalisation of liver biochemistry was 175 days (IQR 70-292 days) from presentation. Three (3/23) were treated with corticosteroids, 14/23 were treated for itch, and one (1/23) underwent liver transplantation. There were no deaths. CONCLUSIONS: The prognosis of DILI from AAS, SARMs and BBS is good although liver transplantation may rarely be required. A detailed drug history is important in uncovering DILI due to these supplements.

Alcohol-Associated Liver Disease: Evolving Concepts and Treatments.

Alcohol is a prominent cause of liver disease worldwide with higher prevalence in developed nations. The spectrum of alcohol-associated liver disease (ALD) encompasses a diverse range of clinical entities, from asymptomatic isolated steatosis to decompensated cirrhosis, and in some cases, acute or chronic liver failure. Consequently, it is important for healthcare practitioners to maintain awareness and systematically screen for ALD. The optimal evaluation and management of ALD necessitates a collaborative approach, incorporating a multidisciplinary team and accounting for concurrent medical conditions. A repertoire of therapeutic interventions exists to support patients in achieving alcohol cessation and sustaining remission, with complete abstinence being the ultimate objective. This review explores the existing therapeutic options for ALD acknowledging geographical discrepancies in accessibility. Recent innovations, including the inclusion of alcohol consumption biomarkers into clinical protocols and the expansion of liver transplantation eligibility to encompass severe alcohol-associated hepatitis, are explored.

Bovine lead exposure from informal battery recycling in India.

We provide an estimate of annual bovine lead exposure and attributable mortality at informal lead acid battery recycling sites in India. We use Pure Earth's Toxic Sites Identification Program database, the FAO's Gridded Livestock dataset, and a Poisson plume model of lead particle air dispersion to estimate site-level mortality. We calculate that India suffers 2370 excess bovine fatalities each year, resulting in more than USD $2.1 million of economic damage. The distribution of damages by location is highly skewed. While we find most sites (86.3%) induce no mortalities, 6.2% of sites induce minor damage (1 to 5 fatalities), 4.1% induce moderate damage (6 to 20 fatalities), and 3.4% induce severe damage (21 + fatalities). These findings highlight the importance of geospatial data to prioritize mitigation efforts and identify a previously unquantified burden on the rural poor.

Hippocampal ischaemia from accidental 5-Hydroxytryptophan (5-HTP) overdose case report.

We report severe reversible hippocampal ischaemia following an accidental 5-Hydroxytryptophan (5-HTP) overdose. Serious consequences from 5-HTP overdose have not been reported. A 44-year-old previously well man ingested ten times the recommended dose of 5-HTP powder. After four hours he developed marked antegrade and retrograde amnesia, disorientation and confusion in the absence of loss of consciousness, seizure activity or features of serotonin toxicity. Magnetic resonance imaging (MRI) of the brain on day two revealed extensive symmetrical restricted diffusion bilaterally in the hippocampi, suggestive of ischaemia or seizure. Electroencephalogram was normal. Short and long-term memory improved sufficiently to return to work after two months. MRI at eleven months was normal. The most likely mechanism is drug-induced hippocampal ischaemia resulting from marked increase in 5-HTP.

Reverse Takotsubo Cardiomyopathy Precipitated by Chronic Cocaine and Cannabis Use.

This case report describes a 31-year-old man with 10 years of cocaine and cannabis dependence who developed reverse Takotsubo cardiomyopathy (rTC), a rare variant of Takotsubo cardiomyopathy. He presented to the Emergency Department (ED) with severe left temporal headache and vomiting which began whilst smoking cannabis and several hours after smoking methamphetamine and using cocaine via insufflation. Computed tomography and angiography of the brain was normal, and the headache resolved with analgesia. Urine drug screen was positive for benzodiazepines, cannabinoids, cocaine, opiates (attributed to morphine administered in ED) and amphetamines. Three hours later he had a seizure and within 10 min developed cardiogenic shock with antero-inferior ST segment depression on electrocardiogram and troponin-T rise to 126 ng/L. Coronary angiography demonstrated normal coronary arteries. Transthoracic echocardiogram demonstrated severely impaired left ventricular (LV) systolic function with ejection fraction 15-20% and hypokinesis sparing the apex. Thyrotoxicosis, nutritional, vasculitic, autoimmune and viral screens were negative. Cardiac magnetic resonance imaging demonstrated severe LV functional impairment with dilated and hypocontractile basal segments, and T2 hyperintensity consistent with myocardial oedema and rTC. He received supportive management. Proposed mechanisms of rTC include catecholamine cardiotoxicity and coronary artery vasospasm. In this case, multiple insults including severe headache, cannabis hyperemesis and cocaine and methamphetamine-induced serotonin toxicity culminated in a drug-induced seizure which led to catecholamine cardiotoxicity resulting in rTC. Clinicians should be cognizant of stress cardiomyopathy as a differential diagnosis in patients with substance use disorders.

Blood lead levels in low-income and middle-income countries: a systematic review.

BACKGROUND: Since the global phase-out of leaded petrol, reports have suggested that lead exposure remains substantial or is increasing in some low-income and middle-income countries (LMICs). However, few studies have attempted to systematically assess blood lead levels over the full range of LMICs. We aimed to describe values for blood lead level in LMICs. METHODS: In this systematic review, we searched PubMed for studies published between Jan 1, 2010, and Oct 31, 2019, that reported blood lead levels in the 137 countries in World Bank LMIC groupings. Studies were reviewed for inclusion if they contained blood lead level data from human populations residing in any given country; comprised at least 30 participants; presented blood lead level data derived from venous, capillary, or umbilical cord samples of whole blood; had data that were collected after Dec 31, 2004; and were published in English. Data on blood lead level were extracted and pooled, as appropriate, to make country-specific estimates of the distribution of background blood lead levels among children and adults, along with information on specific sources of exposure where available. This study is registered with PROSPERO, number CRD42018108706. FINDINGS: Our search yielded 12 695 studies, of which 520 were eligible for inclusion (1100 sampled populations from 49 countries comprising 1 003 455 individuals). Pooled mean blood lead concentrations in children ranged from 1·66 µg/dL (SD 3·31) in Ethiopia to 9·30 µg/dL (11·73) in Palestine, and in adults from 0·39 µg/dL (1·25) in Sudan to 11·36 µg/dL (5·20) in Pakistan. Background values for blood lead level in children could be pooled in 34 countries and were used to estimate background distributions for 1·30 billion of them. 632 million children (95% CI 394 million-780 million; 48·5%) were estimated to have a blood lead level exceeding the US Centers for Disease Control's reference value of 5 µg/dL. Major sources of lead exposure were informal lead acid battery recycling and manufacture, metal mining and processing, electronic waste, and the use of lead as a food adulterant, primarily in spices. INTERPRETATION: Many children have a blood lead level exceeding 5 µg/dL in LMICs, despite leaded petrol phase-outs. Given the toxicity of lead, even at low amounts of exposure, urgent attention is required to control exposures and to expand population-based sampling in countries with no or scant data. FUNDING: This work was supported by the United States Agency for International Development (Cooperative Agreement number AID-OAA-A-16-00019).

Fentanyl and Driving Impairment.

The incidence of fentanyl in forensic toxicology analyses in the USA has dramatically increased over the past several years. The increase in death cases has been well studied; however, little has been reported on the impact to drug impaired driving. Fentanyl driving while under the influence of drugs (DUID) case data from 2014 to 2019 is presented. The data were obtained from three toxicology laboratories in the Northeast, Southeast, and Midwest regions of the USA. Fentanyl whole blood concentrations ranged from 0.1 to 157 ng/mL in living drivers with a 466% to 524% increase in fentanyl-positive DUID cases from 2014 to 2019, depending on the US region. The vast majority of fentanyl cases involved poly-drug use. Twenty case histories are presented where fentanyl was the only drug identified. The mean (standard deviation) fentanyl concentration for these cases was 5.2 ± 3.8 ng/mL with a median of 3.7 ng/mL, and the concentrations ranged from 2.0 to 16 ng/mL. Naloxone administration was documented in exactly half of these cases similar to another study involving carfentanil-impaired driving. The case histories also demonstrate that some recreational opioid users may display limited signs of impairment either due to tolerance or naloxone administration. The top three observations in common among the cases were the driver was found unresponsive behind the wheel, the vehicle left the travel lane or roadway, and the driver was involved in a crash. The increase in fentanyl use not only poses a risk for overdose and death, but is also a significant concern for traffic safety. This study supports the movement of fentanyl from a Tier II drug to Tier I due to its significant potential for impairment and increase in prevalence in impaired driving cases.

Binding characterization of N-(2-chloro-5-thiomethylphenyl)-N'-(3-[3 H]3 methoxy phenyl)-N'-methylguanidine ([3 H]GMOM), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist.

Labeled with carbon-11, N-(2-chloro-5-thiomethylphenyl)-N'-(3-methoxyphenyl)-N'-methylguanidine ([11 C]GMOM) is currently the only positron emission tomography (PET) tracer that has shown selectivity for the ion-channel site of N-methyl-D-aspartate (NMDA) receptors in human imaging studies. The present study reports on the selectivity profile and in vitro binding properties of GMOM. The compound was screened on a panel of 80 targets, and labeled with tritium ([3 H]GMOM). The binding properties of [3 H]GMOM were compared to those of the reference ion-channel ligand [3 H](+)-dizocilpine maleate ([3 H]MK-801), in a set of concentration-response, homologous and heterologous inhibition, and association kinetics assays, performed with repeatedly washed rat forebrain preparations. GMOM was at least 70-fold more selective for NMDA receptors compared to all other targets examined. In homologous inhibition and concentration-response assays, the binding of [3 H]GMOM was regulated by NMDA receptor agonists, albeit in a less prominent manner compared to [3 H]MK-801. Scatchard transformation of homologous inhibition data produced concave upward curves for [3 H]GMOM and [3 H]MK-801. The radioligands showed bi-exponential association kinetics in the presence of 100 µmol L-1 l-glutamate/30 µmol L-1 glycine. [3 H]GMOM (3 nmol L-1 and 10 nmol L-1 ) was inhibited with dual affinity by (+)-MK-801, (R,S)-ketamine and memantine, in both presence and absence of agonists. [3 H]MK-801 (2 nmol L-1 ) was inhibited in a monophasic manner by GMOM under baseline and combined agonist conditions, with an IC50 value of ~19 nmol L-1 . The non-linear Scatchard plots, biphasic inhibition by open channel blockers, and bi-exponential kinetics of [3 H]GMOM indicate a complex mechanism of interaction with the NMDA receptor ionophore. The implications for quantifying the PET signal of [11 C]GMOM are discussed.

Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis.

Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.