The Goiânia incident, the semiotics of danger, and the next 10,000 years.

THE GOIÂNIA INCIDENT: In September 1987, two men in Goiânia, Brazil, discovered an abandoned international standard capsule containing less than 100 g of cesium-137 chloride. The material was unguarded, and the warning systems were inadequate and inscrutable. The men took the capsule and sold it for scrap, and within days the city would be contaminated with highly radioactive material. Within weeks, 112,000 individuals would be screened for radioactive contamination, 249 would be exposed to radioactive materials, 46 would receive medical treatment for radioactive contamination, and four would die from acute radiation sickness. The citywide radioactive contamination occurred, in part, due to arbitrary and unfamiliar written warning systems. The individuals who discovered the cesium-137 capsule were illiterate and unfamiliar with the radiation trefoil logo, which was first used in 1946 in California, United States of America. As a result, written language and visual symbols were useless warnings against the dangerous contents of the capsule. MANAGEMENT OF CESIUM-137 EXPOSURE IN 2023: Cesium-137 enters the body through ingestion or inhalation. This isotope emits beta and gamma radiation, both forms of ionizing radiation which damage living tissues. The radiation dose lethal to 50% of an exposed population within 60 days (LD50/60) is approximately 3.5 to 4 Gray (Gy) without medical intervention. However, this dose increases to around 6-7 Gy when medical support is provided, which typically includes antibiotics, blood transfusions, granulocyte-macrophage colony-stimulating factor, and Prussian blue. Prussian blue binds to cesium, thereby facilitating its elimination from the body. LESSONS LEARNED REGARDING RADIOACTIVE WASTE DISPOSAL AND THE NEXT 10,000 YEARS: The radiological disaster in Goiânia was due in large part to the failures of various agencies to warn of danger and minimize access to radioactive material. Barriers to risk communication included a lack of a universal semiotic language regarding radioactive hazards, which was compounded by the illiteracy of the scrappers and their inability to recognize the radioactivity warning trefoil. There is no society in which every member understands written language or recognizes every symbol. Given that the teletherapy unit was abandoned in an urban environment, there were no administrative or engineering controls in place to prevent human beings from becoming exposed to radioactive material. CONCLUSIONS: As little as 100 g of highly radioactive material, such as cesium-137, may lead to massive environmental contamination, fatalities and permanent disability due to acute radiation sickness, wreak havoc, and disrupt society on a scale that is challenging for public health officials to manage. Thousands of tons of radioactive materials from the waste products of nuclear weapons and power plant manufacture will have to be stored for at least 100,000 years to prevent danger to human life and society. Public health officials and governments must build systems to keep humans safe and physically isolated from these radioactive materials for as long as possible.

Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19.

BACKGROUND: US poison control centers reported increased cases of ivermectin toxicity during the COVID-19 pandemic. Previous descriptions of ivermectin toxicity have evaluated heterogeneous groups with a variety of ivermectin sources and dosage patterns. We sought to compare the clinical effects of ivermectin toxicity in patients taking human- vs. veterinary-formulations and acute- vs. chronic-ingestion patterns. METHODS: We performed a retrospective analysis of cases from the Oregon Poison Center of ivermectin exposures for the prevention or treatment of COVID-19 that resulted in a healthcare visit over a 24-week period (14 August 2021 - 31 January 2022). RESULTS: We identified 37 cases of ivermectin toxicity. The median age of patients was 64 years, and most patients were male. The majority of patients were hospitalized (21) or treated in an emergency department (13). A minority were treated in an outpatient setting (3) and one patient died. Seventeen ingested veterinary formulations and fifteen ingested prescription tablets. Patients reported taking ivermectin for treatment (23) and prevention (14) of COVID-19. Clinical effects included neurotoxicity (30), gastrointestinal symptoms (14), and musculoskeletal complaints (7). Patients taking veterinary products took higher doses of ivermectin and had higher rates of altered mental status than those taking prescription tablets. Patients taking ivermectin chronically took smaller doses (daily dose of 13.5 mg) over a prolonged period (median 3.8 weeks) and developed toxicity that was milder than those with acute ingestions. CONCLUSION: Ivermectin toxicity developed in predominantly male patients >60 years old who ingested higher than recommended doses and developed neurologic symptoms. Patients who took a veterinary formulation of ivermectin ingested large single doses or large daily doses for several days and developed rapid onset of neurotoxicity. Patients with chronic toxicity developed milder symptoms and tended to take typical therapeutic doses, but continued therapy for weeks rather than days.

Efficacy of lipid emulsion therapy in treating cardiotoxicity from diphenhydramine ingestion: a review and analysis of case reports.

INTRODUCTION: Lipid emulsion therapy (LET) has been most thoroughly studied to reverse local anesthetic systemic toxicity (LAST). Case reports suggest that LET can successfully rescue cardiovascular collapse from bupropion, amitriptyline, and propranolol. The efficacy of LET against refractory hypotension and dysrhythmias from diphenhydramine, a commonly ingested lipophilic cardiotoxic agent, is less well described. OBJECTIVE: Summarize the evidence that LET rescues cardiac ion channel blockade (QRS, QTc widening) or hypotension attributable to diphenhydramine overdose. METHODS: We searched MEDLINE, EMBASE, and Google Scholar for English-language full-length case reports of diphenhydramine (DPH) intoxication in patients 17 years of age or older. We extracted data with a PRISMA-compliant protocol, dividing the case reports into two groups, one that received LET and one that did not. We performed a pooled analysis to compare the change in mean arterial pressure (MAP), QRS duration, and QTc duration between the two groups. RESULTS: We identified 23 reports (25 patients). Lipid emulsion therapy (LET) was used in 6 cases because the patient suffered from hypotension refractory to traditional resuscitation. Those who received LET and those who did not were comparable in age, gender, amount ingested, and frequency of seizures. The mean arterial pressure (MAP) decreased by 4.5 ± 11.5 mm Hg in those who did not receive LET compared to an increase in MAP 37 ± 17.5 mm Hg in those who did receive LET. The QRS narrowed by 29 ± 33.9 ms (no LET group) vs 68 ± 49.5 ms (LET group) and QTc by 168.5 ± 126.75 ms (no LET group) vs 134 ± 88 ms (LET group). All values are expressed as median ± interquartile range. One out of the 6 patients who received LET died after withdrawal of care. In the group that did not receive LET 4 out of 19 died and 3 had no outcome reported. DISCUSSION: LET may improve MAP in patients with hypotension refractory to vasopressors due to diphenhydramine toxicity. We found no significant effect of LET on QRS or QTc duration. These results are limited by a small sample size, reporting bias of case reports, incomplete data, and heterogeneity. CONCLUSION: An analysis of pooled case reports suggests that LET may rescue hypotension when other methods have failed in patients with hypotension attributable to diphenhydramine overdose.

Death due to sepsis in patients diagnosed with prostate cancer.

BACKGROUND: To examine the prevalence and determinants of death due to sepsis in patients diagnosed with prostate cancer (Pca). PATIENTS AND METHODS: We performed a retrospective analysis of 910 986 patients diagnosed with Pca between 1992 and 2010 identified from the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence of death due to sepsis after diagnosis was determined. Trends in incidence-based mortality rate (IBMR) due to sepsis were compared with those of patients diagnosed with other common cancers. Competing risk analysis was utilized to examine the determinants of the endpoint of sepsis-specific death (SSD) in Pca patients. RESULTS: Of the Pca patients examined, 2593 died because of sepsis. Sepsis-related IBMR in Pca patients increased by 19-folds from 0.62/1000 000 in 1992-12.26/1000 000 in 2010. Compared with other selected cancers, patients with Pca had the highest IBMR due to sepsis post-cancer diagnosis, and the highest annual percentage change in IBMR due to sepsis (average annual percentage change, 13.1%; 95%CI, 9.4-16.9%). Age, race, education, marital status, and definitive therapy were all significant predictors of death due to sepsis after Pca diagnosis (all P values < 0.05). CONCLUSION: Patients diagnosed with Pca are at increased risk of dying from sepsis, and the sepsis-related IBMR in these patients is increasing over time. There are significant disparities in the outcome of sepsis among Pca patients that require further research.

A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome.

OBJECTIVE: To quantify reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS), create a demographic of patient reports, and examine the cluster of symptoms to correlate consistency of postfinasteride syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster of sexual, physical, and psychological and/or neurologic symptoms associated with 5-alpha reductase inhibitor use that emerge or continue after discontinuation of medication. MATERIALS AND METHODS: FAERS dataset of 5-alpha reductase inhibitors from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories for completion, but not every report was fully completed. Statistical analysis compared variables of interest between the 2 doses of finasteride (1 mg vs 5 mg). RESULTS: From FAERS, 2048 monotherapy cases were identified: 1581 of finasteride 1 mg, 240 of finasteride 5 mg, and 226 of unreported doses. Possibly related to labeling changes, from 2011 to 2014, there was a significant increase in adverse events (AEs) reported involving 1 mg dosing. Finasteride use was reported with many sexual AEs including diminished libido, erectile dysfunction, and ejaculatory complaints. Other common AEs included dermatologic, metabolic, and psychological and/or neurologic complaints. There were more AE reports with the 1 mg dose than the 5 mg dose. One case of dutasteride reported back pain, not generally attributed to PFS. CONCLUSION: FAERS data suggests that finasteride exposure is reported with a diverse collection of symptoms, particularly in younger men on 1 mg dosage compared to older men on 5 mg. Many of these complaints fall well out of the realm of previously established AEs from long-term controlled studies.

Impact of Urologist Density and County Rurality on the Practice of Retroperitoneal Lymph Node Dissection and Cancer-Specific Death in Patients with Nonseminomatous Germ Cell Tumors.

PURPOSE: To investigate the impact of rural status and urologist density on the practice of retroperitoneal lymph node dissection (RPLND) and cancer-specific death (CSD) in patients with nonseminomatous germ cell tumor (NSGCT). METHODS: Urologist density was determined from 2014 to 2015 Area Health Resource File data, and rural residence was determined using the 2003 Rural-Urban Continuum Codes. All cases of NSGCT within Surveillance, Epidemiology and End Results (SEER) 18 with known county code were used for analysis (n = 9473). Fisher's exact test, t-tests, and Cox proportional hazard analysis were used to examine the association between variables of interest and study endpoints. RESULTS: Overall, 26.7% of cases lived in a county with less than the mean urologist density, 6.23% lived in counties with no urologists, 9.0% lived in a rural county, and 23.1% (n = 2208) had RPLND performed. RPLND was performed more in cases who lived in a county with a urologist and more in cases with urban residence (p < 0.05). The mean number of lymph nodes examined was lower in patients who lived in rural counties and counties with fewer urologists (p < 0.05). There was no difference in the number of positive nodes dependent upon either urologist density categorization or rurality (p > 0.05). Rurality and low urologist density were not associated with a higher risk of CSD related to NSGCT. CONCLUSIONS: Patient's residence and access to urologists affect their surgical NSGCT treatment, and efforts aimed at improving access to high-quality RPLND may be indicated.

Trichloroethylene Is Associated with Kidney Cancer Mortality: A Population-based Analysis.

AIM: To examine the association between the distribution of trichloroethylene (TCE) exposure and mortality from kidney cancer (Kca) across United States counties. MATERIALS AND METHODS: Multiple linear regression was used to assess the association of TCE discharges from industrial sites and age-adjusted incidence and mortality rates for Kca during 2005 through 2010, controlling for confounders. A total of 163 counties were included in analysis. RESULTS: We observed an excess risk of Kca mortality associated with higher amounts of environmental TCE releases. A significant dose-response relationship was observed between TCE releases and Kca mortality in females. Smoking, education, income, hypertension, and obesity were significant predictors of incidence and mortality, consistent with previous research on the epidemiology of Kca. CONCLUSION: TCE exposure may increase the risk of mortality from Kca, an association not highlighted before. There is a need for policy measures to limit TCE discharge to the environment if these results are validated.