National Prevalence of Alcohol and Other Substance Use Disorders Among Emergency Department Visits and Hospitalizations: NHAMCS 2014-2018.

BACKGROUND: Acute healthcare utilization attributed to alcohol use disorders (AUD) and other substance use disorders (SUD) is rising. OBJECTIVE: To describe the prevalence and characteristics of emergency department (ED) visits and hospitalizations made by adults with AUD or SUD. DESIGN, SETTING, AND PARTICIPANTS: Observational study with retrospective analysis of the National Hospital Ambulatory Medical Care Survey (2014 to 2018), a nationally representative survey of acute care visits with information on the presence of AUD or SUD abstracted from the medical chart. MAIN MEASURES: Outcome measured as the presence of AUD or SUD. KEY RESULTS: From 2014 to 2018, the annual average prevalence of AUD or SUD was 9.4% of ED visits (9.3 million visits) and 11.9% hospitalizations (1.4 million hospitalizations). Both estimates increased over time (30% and 57% relative increase for ED visits and hospitalizations, respectively, from 2014 to 2018). ED visits and hospitalizations from individuals with AUD or SUD, compared to individuals with neither AUD nor SUD, had higher percentages of Medicaid insurance (ED visits: AUD: 33.1%, SUD: 35.0%, neither: 24.4%; hospitalizations: AUD: 30.7%, SUD: 36.3%, neither: 14.8%); homelessness (ED visits: AUD: 6.2%, SUD 4.4%, neither 0.4%; hospitalizations: AUD: 5.9%, SUD 7.3%, neither: 0.4%); coexisting depression (ED visits: AUD: 26.3%, SUD 24.7%, neither 10.5%; hospitalizations: AUD: 33.5%, SUD 35.3%, neither: 13.9%); and injury/trauma (ED visits: AUD: 51.3%, SUD 36.3%, neither: 26.4%; hospitalizations: AUD: 31.8%, SUD: 23.8%, neither: 15.0%). CONCLUSIONS: In this nationally representative study, 1 in 11 ED visits and 1 in 9 hospitalizations were made by adults with AUD or SUD, and both increased over time. These estimates are higher or similar than previous national estimates using claims data. This highlights the importance of identifying opportunities to address AUD and SUD in acute care settings in tandem with other medical concerns, particularly among visits presenting with injury, trauma, or coexisting depression.

NAloxone CARdiac Arrest Decision Instruments (NACARDI) for targeted antidotal therapy in occult opioid overdose precipitated cardiac arrest.

BACKGROUND: We have recently demonstrated that a significant proportion of fatal out-of-hospital cardiac arrests (OHCAs) are precipitated by occult overdose, which could benefit from antidote therapy administered adjunctively with other cardiac resuscitation measures. We sought to develop simple decision instruments that EMS providers and other first responders can use to rapidly identify occult opioid overdose-associated OHCAs. METHODS: We examined data from February 2011 through December 2017 in the Postmortem Systematic Investigation of Sudden Cardiac Death study, in which San Francisco (California) County EMS-attended OHCA deaths received autopsy and expert panel adjudication of cause of death. Using classification tree analyses, we derived highly sensitive and specific decision instruments that predicted our primary outcome of occult opioid OD-associated OHCA. We then calculated screening performance characteristics of these instruments. RESULTS: Of 767 OHCA deaths, 80 (10.4%) were associated with occult opioid overdose. Of the eight models with 100% sensitivity for opioid overdose-associated cardiac arrest, the highest specificity model (23.4%, 95% confidence interval [CI] 20.3-26.7%) was age < 60 years OR race = black or non-Latinx white OR arrest in public place. The highest specificity instrument (96.3%, 95% CI 94.6-97.5%) consisting of age < 60 years AND race = black or non-Latinx white AND unwitnessed arrest AND female sex had 25% (95% CI 16-35.9%) sensitivity. CONCLUSIONS: We have derived simple decision instruments that can identify patients whose OHCA precipitant was occult opioid overdose. These instruments may be used to guide selective administration of the antidote naloxone in OHCA resuscitations.

Severe Methemoglobinemia and Death From Intentional Sodium Nitrite Ingestions.

BACKGROUND: Sodium nitrite is known to induce methemoglobinemia and hypotension when ingested, but reports of intentional ingestion remain rare. CASE SERIES: We report five cases of severe methemoglobinemia secondary to large sodium nitrite ingestion that were reported to and managed by the California Poison Control System in 2019, resulting in three fatalities. The estimated doses ingested ranged from 15 grams to 113 grams, with one patient surviving after an ingestion of 60 grams. The highest documented methemoglobin level was 73%. The 2 patients who survived received methylene blue early in their clinical course. One patient required higher doses of methylene blue compared with other cases of nitrite-associated methemoglobinemia. In the patients who survived, all symptoms resolved within 24 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These cases highlight the severe toxicity associated with intentional large sodium nitrite ingestion. In management, consideration should be given to administering higher initial or more frequent doses of methylene blue compared with standard practice. Given that sodium nitrite is readily accessible through online vendors, and is being circulated through various suicide forums, it has the potential to be more commonly encountered in the emergency department.

Real-time comprehensive toxicology testing in the clinical management of accidental pediatric capecitabine ingestion.

INTRODUCTION: Capecitabine is an orally bioavailable prodrug of the chemotherapeutic agent, fluorouracil. Fluorouracil is converted to several active metabolites that induce a cytotoxic effect. Capecitabine toxicity can be life-threatening with a delayed presentation from ingestion. An oral antidote, uridine triacetate, exists but requires the administration of 20 total doses over a course of five days. CASE REPORT: In this report, we describe a case where timely coordination with a clinical toxicology laboratory was utilized to drive clinical decision making and management. Two children were brought to the emergency department shortly after suspected capecitabine ingestion. MANAGEMENT AND OUTCOME: Patients were admitted to the hospital and started on uridine triacetate. Real-time comprehensive toxicology testing of the children's blood was used to rule out capecitabine toxicity and prevent several unnecessary days of hospitalization and doses of antidote. Patients were discharged safely. DISCUSSION: Real-time comprehensive toxicology testing on a patient's blood may be a valuable resource in ruling out or confirming toxic exposure in accidental pediatric ingestion of chemotherapeutic agents like capecitabine when performed in a timely manner.

An interprofessional clinical toxicology advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: Clinical toxicology is a blend of science, research, and patient management practices involving human poisonings from exposure to natural and synthetic toxins. The objective of this study was to describe the components of an elective advanced pharmacy practice experience (APPE) in clinical toxicology at California Poison Control System (CPCS). EDUCATIONAL ACTIVITY AND SETTING: The APPE requirements included a mix of active participation in case management and supplemental educational exercises, case presentations and consultations, and a structured self-study component consisting of readings and on-line modules. In addition, there were two active learning activities, high acuity poisoning simulation scenarios utilizing a high-fidelity mannequin, and an antidote tasting session. FINDINGS: From April 2012 to October 2017, 82 student pharmacists completed this APPE. Pharmacy students completed 85 pre-simulation surveys and 80 post-simulation surveys. Survey results showed an increase in pharmacy student beliefs that a clinical pharmacist should be involved in the differential diagnosis and management of patients (60% pre-simulation vs. 78.8% post-simulation, p = 0.009). APPE pharmacy students completed an evaluation of the preceptors(s), site, and learning experience. The average score for all areas on the preceptor and site evaluations was >4.5 on a 5-point Likert scale. Qualitative data themes included student satisfaction with opportunities, feedback, and the interprofessional and collaborative environment. SUMMARY: An APPE in the CPCS was successfully designed and implemented. The APPE provides an interprofessional collaborative learning environment that allows student pharmacists to understand the unique role of the pharmacist in this setting.

Electrophysiologic similarities of overdose between digoxin and bufadienolides found in a Chinese aphrodisiac.

Classically derived from toad venom, bufadienolides are a group of cardioactive steroids with properties similar to digoxin. Some traditional Chinese medications, including several aphrodisiacs, contain bufadienolides. Owing to their physiologic similarities to digoxin, bufadienolides have been shown to produce a toxic profile similar to that of digoxin and there have been multiple case reports of the use of these aphrodisiacs resulting in death. This report will describe a case that illustrates the electrophysiologic similarities between bufadienolide toxicity and digoxin toxicity as well as the treatment of bufadienolide toxicity.

Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations.

BACKGROUND: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. CASE REPORT: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. CONCLUSION: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.

Can biochemical abnormalities predict symptomatology in patients with primary hyperparathyroidism?

BACKGROUND: Primary hyperparathyroidism presents with a myriad of symptoms, which range in severity. The cause of these symptoms is not well understood. We sought to determine if the severity of preoperative biochemical abnormalities (calcium, parathyroid hormone, vitamin D levels) correlated with symptomatology in patients undergoing surgical treatment for primary hyperparathyroidism. STUDY DESIGN: Over 15 months, 229 consecutive patients with primary hyperparathyroidism completed a symptom questionnaire before parathyroidectomy. The symptom profiles of patients with significant hypercalcemia at initial presentation (≥11.2 mg/dL) and those with baseline calcium levels (<11.2 mg/dL) were compared. The patients were also categorized based on parathyroid hormone (< or ≥130 pg/mL) and vitamin D (< or ≥30 ng/mL) and analyzed in a similar manner. RESULTS: Seventy-eight patients (34%) had a baseline calcium ≥11.2 mg/dL, but compared with patients with calcium <11.2 mg/dL, only the incidence of nephrolithiasis was more common in those patients with significant hypercalcemia (18% vs 9%, p = 0.04). Conversely, depression, bone or joint pain, and constipation were all significantly more common in patients with calcium <11.2mg/dL (p = 0.006, 0.001, and 0.031, respectively). Patients analyzed based on parathyroid hormone and vitamin D levels showed no significant difference in symptom presentation. CONCLUSIONS: These data indicate that the degree of parathyroid hormone elevation and the presence of vitamin D deficiency do not correlate with the presence of symptoms in patients with primary hyperparathyroidism. Significant hypercalcemia was associated with nephrolithiasis, but interestingly, patients with milder hypercalcemia had significantly more depression, bone or joint pain, and constipation, suggesting that these symptoms are likely not mediated by hypercalcemia.

Neurocognitive dysfunction: a predictor of parathyroid hyperplasia.

BACKGROUND: To determine whether a symptomatic presentation was associated with parathyroid hyperplasia, we retrospectively examined pre-operative symptom profiles of patients who underwent parathyroidectomy. METHODS: From October 2007 to July 2008, 111 patients with primary hyperparathyroidism completed a preoperative symptom questionnaire prior to parathyroidectomy. The symptom profiles of patients with and without hyperplasia were compared. RESULTS: Neurocognitive symptoms occurred in 51.4% of patients. Patients with 1 neurocognitive symptom had a 25% risk of parathyroid hyperplasia. Additional neurocognitive symptoms increased the risk of hyperplasia linearly, with hyperplasia occurring in 38% of patients reporting 2 neurocognitive symptoms (P < .001) and 61% of patients reporting 3 or more of these symptoms (P < .001). A negative sestamibi scan was associated with a 33% risk of hyperplasia. Coupled with at least 1 neurocognitive symptom, the risk of hyperplasia was 53.3% (P < .001). Of patients with 3 or more neurocognitive symptoms and a negative localizing scan, 100% were found to have parathyroid hyperplasia (P < .001). CONCLUSION: The presence of neurocognitive dysfunction in a patient with hyperparathyroidism may be used as a predictor of hyperplastic disease. Three or more of these symptoms, coupled with a negative sestamibi scan, was 100% predictive of parathyroid hyperplasia in our cohort.

Older age and larger tumor size predict malignancy in hürthle cell neoplasms of the thyroid.

BACKGROUND: Hürthle cell neoplasms (HCNs) are rare tumors of the thyroid gland. The definitive treatment for Hürthle cell carcinoma (HCC) is total thyroidectomy, while thyroid lobectomy is adequate for Hürthle cell adenoma (HCA). However, differentiating HCC from HCA either before or during surgery is a challenge. The purpose of this study was to identify factors that predict malignancy in patients with HCN. METHODS: Between May 1994 and January 2007, 1,199 patients underwent thyroid surgery at an academic medical center. Medical records of 55 consecutive patients who underwent thyroid resections for the preoperative diagnosis of HCN were reviewed. RESULTS: Of the 55 patients with HCN, 46 (84%) had adenomas and 9 (16%) had carcinomas. Patients with HCC were significantly older than those with HCA (66 +/- 6 years versus 53 +/- 2 years, P = 0.01). Patients with carcinoma also had significantly larger thyroid nodules (4.5 +/- 0.7 cm versus 2.5 +/- 0.2 cm, P < 0.001). All HCNs less than 2 cm in diameter were benign. The malignancy rate increased with nodule size: 18% of nodules measuring 2-4 cm, and 44% of those larger than 4 cm were HCC. One patient with HCC had recurrence of the disease, but there were no disease-related deaths. CONCLUSION: Advanced patient age and larger nodule size are two important factors that predict malignancy in patients with HCN. In patients with these and other known risk factors for HCC, total thyroidectomy should be considered.

Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage.

CONTEXT: TSH is a known thyroid growth factor, but the pathogenic role of TSH in thyroid oncogenesis is unclear. OBJECTIVE: The aim was to examine the relationship between preoperative TSH and differentiated thyroid cancer (DTC). DESIGN: The design was a retrospective cohort. SETTING, PARTICIPANTS: Between May 1994 and January 2007, 1198 patients underwent thyroid surgery at a single hospital. Data from the 843 patients with preoperative serum TSH concentration were recorded. MAIN OUTCOME MEASURES: Serum TSH concentration was measured with a sensitive assay. Diagnoses of DTC vs. benign thyroid disease were based on surgical pathology reports. RESULTS: Twenty-nine percent of patients (241 of 843) had DTC on final pathology. On both univariate and multivariable analyses, risk of malignancy correlated with higher TSH level (P=0.007). The likelihood of malignancy was 16% (nine of 55) when TSH was less than 0.06 mIU/liter vs. 52% (15 of 29) when 5.00 mIU/liter or greater (P=0.001). When TSH was between 0.40 and 1.39 mIU/liter, the likelihood of malignancy was 25% (85 of 347) vs. 35% (109 of 308) when TSH was between 1.40 and 4.99 mIU/liter (P=0.002). The mean TSH was 4.9+/-1.5 mIU/liter in patients with stage III/IV disease vs. 2.1+/-0.2 mIU/liter in patients with stage I/II disease (P=0.002). CONCLUSIONS: The likelihood of thyroid cancer increases with higher serum TSH concentration. Even within normal TSH ranges, a TSH level above the population mean is associated with significantly greater likelihood of thyroid cancer than a TSH below the mean. Shown for the first time, higher TSH level is associated with advanced stage DTC.

Is Hashimoto's thyroiditis a risk factor for papillary thyroid cancer?

BACKGROUND: Hashimoto's thyroiditis (HT) is the most common cause of hypothyroidism and is characterized by gradual autoimmune mediated thyroid failure with occasional goiter development. HT is seven times more likely to occur in women than in men. Papillary thyroid cancer (PTC), the most prevalent form of cancer in the thyroid, is 2.5 times more likely to develop in women than men. Given the relatively high prevalence of these diseases and the increased occurrence in women, we analyzed data from our institution to determine if there is a correlation between Hashimoto's thyroiditis and PTC in women. METHODS: From May 1994 to January 2007, 1198 patients underwent thyroid surgery at our institution. Of these, 217 patients were diagnosed with HT (196 women, 21 men). The data from these patients were statistically analyzed using SPSS. RESULTS: PTC occurred in 63 of 217 (29%) HT patients and 230 of 981 (23%) patients without HT (P = 0.051). Of these groups, 41 (65%) and 158 (69%) patients, respectively, had tumor sizes >/=1.0 cm; 56/196 women (29%) with HT had coexistent PTC compared with 160/730 women (22%) without HT (P = 0.03). Among women with any type of thyroid malignancy, 56/59 cases (95%) with HT had PTC compared with 159/196 cases (81%) in women without HT (P = 0.006). Additionally, female HT patients with goiters had a significantly lower rate of PTC (9% versus 36%, P < 0.001) compared with women without goiters. These differences were not observed in men with HT. CONCLUSIONS: These data demonstrate that HT is associated with an increased risk of developing PTC. Female patients with HT undergoing thyroidectomy are 30% more likely to have PTC. Thus, more aggressive surveillance for PTC may be indicated in patients with HT, especially in women.

Is tumor size the best predictor of outcome for papillary thyroid cancer?

BACKGROUND: There are many risk classification schemes that determine both treatment and outcome for patients with papillary thyroid cancer. Most of these formulas often utilize tumor size as the key predictor of outcome. Furthermore, there is no clear consensus regarding the treatment of small papillary cancers. Therefore, we reviewed our experience in order to determine which factors best predict outcome for papillary thyroid cancer. In addition, we sought to establish a tumor size threshold beyond which papillary cancers require treatment. METHODS: From May 1994 to October 2004, 174 patients underwent surgery for papillary thyroid cancer (PTC) at our institution. These patients were divided into five groups based on tumor size. The data from these groups were analyzed utilizing ANOVA, Chi-square and linear regression analysis. RESULTS: The mean age of the patients was 42 +/- 1 years and 126 (72%) were female. Mean tumor size was 17.2 +/- 1.1 mm. The overall outcome was quite good with a survival rate of 97% and a recurrence rate of 12%. On univariate analysis, there was no difference amongst the groups in regards to age or gender. However, there was a significantly higher incidence of lymph node metastasis amongst those with the largest tumors. Consequently, those patients with the largest tumors were treated more aggressively, with 75% undergoing total thyroidectomies and 85% receiving radioactive iodine therapy. However, on univariate and multivariate analysis, tumor size was not shown to correlate with higher recurrence. Rather, the only factor associated with a greater recurrence rate was the presence of lymph node metastases. CONCLUSION: At our institution, the recurrence rates for PTC were similar for all sizes of tumors. Furthermore, presence of metastatic disease at the time of diagnosis, rather than tumor size, seems to be a better predictor of recurrence and outcome.