Impact of Faculty Incentivization on Resident Evaluations.

INTRODUCTION: In the Program Requirements for Graduate Medical Education in Emergency Medicine, the Accreditation Council for Graduate Medical Education requires frequent and routine feedback. It is a common challenge for program leadership to obtain adequate and effective summative evaluations. METHODS: This is a retrospective, case-crossover, interventional study conducted in an academic medical center. This study occurred over a two-year period, with an intervention between years one and two. Throughout year two of the study, faculty incentive compensation was linked to completion of end-of-shift evaluations. We compared pre- an post-implementation data using paired sample t-tests with the significance level P < .05 applied. RESULTS: After implementation of the incentive metric there was an increase in the number of total evaluations by 42% (P = .001). The mean number of evaluations submitted by each faculty per shift increased from 0.45 to 0.86 (SD 0.56, P < .001). Overall, 32 of the 38 faculty members (84.2%) had an increase in the number of evaluations submitted per shift during the intervention period with an average increase of 0.5 evaluations per shift (range 0.01-1.54). CONCLUSION: Incentivizing faculty to submit resident evaluations through use of bonus compensation increased the number of evaluations at our institution. This information may be applied by other programs to increase resident evaluations.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Sex Differences in Substance Use and Misuse: A Toxicology Investigators' Consortium (ToxIC) Registry Analysis.

BACKGROUND: Variations between male and female populations are previously reported in classes of harmfully used/misused drugs, severity of substance use disorder and risk of relapse. The aim of this study was to provide a review of bedside medical toxicologist managed, sex-specific poisonings in adults that present with harmful drug use/misuse. METHODS: ToxIC Registry cases ≥19 and ≤65 years old, with harmful drug use or misuse during the timeframe June 2010-December 2016, were studied. Demographics, primary agents of toxic exposure, administration route and complications were analyzed. Descriptive methods were used in the analysis. RESULTS: The database included 51,440 cases. Of these, 3426 cases were analyzed in which the primary reason for the encounter was harmful substance use/misuse. Females were found to harmfully use/misuse pharmaceutical drugs (N=806, 65.6%) more than nonpharmaceutical drugs (N=423, 34.4%). Males more frequently used nonpharmaceutical drugs (N=1189, 54.1%) than pharmaceutical drugs (1008, 45.9%). Analgesics were used by females (N= 215, 18.2%) and males (N=137, 6.6%). Sedative hypnotics were used by females (N=165, 14%) and males (N=160, 7.8%). Psychoactive agents were used by males (N=325, 15.8%) and females (N=67, 5.7%). Sympathomimetics were used by males (N=381, 18.5%) and females (N=151, 12.8%). The majority of both male and female participants, 1712 (57.9%), utilized an oral route of administration. However, 312 (16.5%) of males utilized inhalation vs 73 (6.8%) of females inhaled their substance. CONCLUSION: There were sex-specific differences among patients evaluated for harmful substance use/misuse by toxicologists. Considering these differences in regards to management and preventive approaches may be indicated.

Sex Differences in Pediatric Poisonings by Age Group: a Toxicology Investigators' Consortium (ToxIC) Analysis (2010-2016).

OBJECTIVE: To review pediatric poisonings evaluated at the bedside by medical toxicologists and reported in the ToxIC registry, by sex and age group. METHODS: Pediatric poisoning cases age ≤18 years, reported between January 2010 and December 2016, were reviewed. Descriptive statistics were used to describe study variables by age group and sex. RESULTS: A total of 12,699 cases were analyzed. There were 7517 females and 5182 males. Those < 2 years old represented 12.5% of the study group (n = 1584), 17.2% were 2-6 years old (n = 2178), 8.6% were 7-12 years old (n = 1097), and 61.7% were 13-18 years old (n = 7840). The most common primary reasons for encounter were intentional pharmaceutical with 4900 females and 1836 males; intentional non-pharmaceutical with 952 females and 1213 males; unintentional pharmaceutical with 539 females and 644 males; and unintentional non-pharmaceutical with 435 females and 593 males. Overall, pharmaceuticals were the most commonly involved agents, including analgesics (20.9% of cases) and antidepressants (11% of cases): 27.8% of females and 10.7% of males were reportedly exposed to an analgesic.13.7% of females and 7.0% of males were reportedly exposed to an antidepressant. Among 1584 cases under 2 years, there were 747 females and 837 males; among 2178 cases aged 2-6 years, there were 954 females and 1224 males; among 1097 cases aged 7-12 years, there were 555 females and 542 males; and among 7840 cases aged 13-18 years, there were 5261 females and 2579 males. Death was reported in 0.7% of the cases: 20 females and 18 males. 6.1% of cases were managed with intubation: 421 females and 351 males. CONCLUSIONS: Sex-based characteristics of poisonings varied by age group among pediatric poisoning presentations reported to the ToxIC registry and further research is needed to determine implications for education and prevention efforts.

Sex differences in patients with suicidal intent that are managed by toxicologists: An analysis of the Toxicology Investigators' Consortium (ToxIC) Registry.

INTRODUCTION: The Toxicology Investigator's Consortium (ToxIC) maintains a prospective case registry of all patients that have been managed at the bedside by medical toxicologists. We set out to characterize the differences in toxicological suicide attempts between men and women among adult patients with poisonings managed by medical toxicologists. METHODS: ToxIC database consults for adults aged 19-65 whose primary reasons for encounter were classified as suicide attempt were used for this study (1/2010-12/2016). Data used for analysis included primary agents of toxic exposure, routes of administration, and complications. The statistical analysis was limited to descriptive methods. RESULTS: Out of 51,440 registry cases, 33,259 cases remained for analysis after applying the ages 19-65 and removing those without complete data. Of these, there were 4827 suicide attempts (14.5% of toxicological exposures) which were sub classified by gender. There were more females (F) than males (M) whose toxicology consults were due to suicidal attempts (57.6% versus 42.4%). We also found that more males used alcohol as their primary agent (2.8%M v 1.5%F) or a nonpharmaceutical (%7.4 M v %2.3 F). CONCLUSIONS: In our study, we found that there were more females than males who attempted suicide by self-poisoning; and more of them used pharmaceuticals than males. In contrast, a greater number of males used nonpharmaceuticals such as alcohol. We did not find large sex-differences in suicide completion rates, routes of administration, or subsequent symptomologies. In summary, sex-based differences were observed between adult patients with suicidal-intent exposures/ingestions managed at the bedside by medical toxicologists.

Interest in and barriers to participation in a Facebook-delivered weight loss program among female cancer survivors with overweight or obesity.

BACKGROUND: Although excess body weight is linked to post-treatment complications for cancer survivors, obesity rates have increased rapidly among adult cancer survivors. Innovative approaches to weight loss programs, such as via social media, are needed to engage female cancer survivors. The purpose of this study is to explore important components of a Facebook-delivered weight loss program for female cancer survivors. METHODS: Female cancer survivors who are overweight or obese and finished active treatment completed a web-based, mixed-methods survey. RESULTS: Participants (N=96) were on average 54.3±9.6 years old, 89% white, 66% obese, and 87% tried to lose weight in the last year. Health concerns were the most important reason (88%) for wanting to lose weight. Barriers to weight loss included other health issues (52%) and perceived sacrifice/burden of weight loss process (35%). Qualitative themes for barriers included inability to make dietary changes (19%), lack of motivation (18%), and physical limitations (13%). Participants were most interested in a weight loss program delivered via Facebook (81%), led by a weight loss counselor (78%), provided healthy recipes (73%) and exercise videos (72%). Qualitative themes included information on cancer treatment effects (25%), calorie tracker (21%), and exercise modifications (17%). Qualitatively, concerns about weight loss included fear of cancer recurrence (20%) and lack of confidence in weight loss efforts (17%). CONCLUSIONS: While female cancer survivors are interested in a Facebook-delivered weight loss program, additional research needs to address customization and delivery to address specific barriers experienced by cancer survivors.

Sex Differences in Poisonings Among Older Adults: An Analysis of the Toxicology Investigators Consortium (ToxIC) Registry, 2010 to 2016.

PURPOSE: Adults aged >65 years are susceptible to intentional and unintentional poisoning, with contributing factors that include polypharmacy, comorbidity, susceptibility to medication error, and gaps in research. Although toxicologists are often tasked with managing and preventing poisoning among older adults, little is known about sex differences in these poisonings. The aim of this study was to review sex differences in poisonings among older adults managed at the bedside by medical toxicologists. METHODS: All case subjects aged >65 years in the Toxicology Investigators Consortium (ToxIC) registry between January 2010 and December 2016 were reviewed. Data included reasons for exposure and consultation, exposure agents and routes, presenting clinical findings, and treatment provided. Cases missing age, sex, or primary reason for toxicology consultation data were excluded. We used χ2 tests to assess differences in distribution of study variables according to participant sex. FINDINGS: Among 51,441 total registry cases, 542 (1.05%) were excluded because of missing data. Among the remaining 50,899 cases, 2930 (5.8%) were included for age >65 years; 52.3% of older adults were female. Race was missing or unknown for 49.2% of cases. Adverse drug reactions were more commonly encountered in female subjects than in their male counterparts (9.6% vs 6.4%; P = 0.001). No statistically significant sex differences were observed for total numbers of intentional, unintentional pharmaceutical, and nonpharmaceutical exposures. The most common medications involved were cardiovascular (16.8%) and analgesics/opioids (14.8%). Female subjects were more likely than male subjects to be evaluated by a toxicologist for cardiovascular medications (18.7% vs 14.7%; P = 0.004) and analgesics/opioids (17.6% vs 11.8%; P < 0.001). Male subjects were more likely than female subjects to be evaluated for ethanol toxicity (7.4% vs 1%; P < 0.001) and for envenomations (4.2% vs 1.8%; P < 0.001). The most common route of exposure was oral ingestion (81.3%). Signs/symptoms were noted in 54.8% of cases, with the most common abnormal vital sign being bradycardia (17.2%). Pharmacologic support was the most common intervention and was more common in male subjects than in female subjects (17.7% vs 12.3%; P < 0.001). Deaths were reported in 38 female subjects (2.45%) and 46 male subjects (3.34%); there was no statistically significant difference in death rate according to sex (P = 0.148). IMPLICATIONS: Older female adults were more commonly evaluated by a medical toxicologist for an adverse drug reaction than older male adults. Female patients were more likely than male patients to be evaluated for poisoning related to analgesic/opioids and cardiovascular medications, and older male patients more frequently received pharmacologic support than older female patients. No significant sex differences were observed in numbers of toxicology consultations for intentional, unintentional pharmaceutical, and nonpharmaceutical exposures.

SoMe and Self Harm: The use of social media in depressed and suicidal youth.

Increased access and use of social media on smartphones and tablets have changed interpersonal communication styles. Because of the ease of social media access and the ability to reach a large number of individuals, social media is an ever more important modality that connects individuals. Importantly, adolescents have adopted social media platforms to discuss issues related to mental health. There is little existing data regarding how adolescents who are depressed or suicidal use social media prior to treatment in the emergency department (ED) for medical care of their psychiatric illness. In this paper, we present formative evidence of social media behaviors in 29 adolescents seeking emergency care for depression or suicidal ideation. Participants were surveyed regarding social media use and motivations to post content regarding depression, death or dying. Among the participants who allowed the research team to view their social media accounts, 40% (n=6) posted content related to depression, death or dying, while 20% (n=3) wrote that they felt depressed and 13.3% (n=2) posted that they wanted to die. Qualitative discussions with participants provided description of reasons for posting content on social media about depression, death and dying, or reasons that individuals refrained from posting online. Despite methodological and technical challenges in research, social media may prove be valuable in detection and intervention of adolescents who are depressed and contemplating suicide.

Methods for Evaluating the Content, Usability, and Efficacy of Commercial Mobile Health Apps.

Commercial mobile apps for health behavior change are flourishing in the marketplace, but little evidence exists to support their use. This paper summarizes methods for evaluating the content, usability, and efficacy of commercially available health apps. Content analyses can be used to compare app features with clinical guidelines, evidence-based protocols, and behavior change techniques. Usability testing can establish how well an app functions and serves its intended purpose for a target population. Observational studies can explore the association between use and clinical and behavioral outcomes. Finally, efficacy testing can establish whether a commercial app impacts an outcome of interest via a variety of study designs, including randomized trials, multiphase optimization studies, and N-of-1 studies. Evidence in all these forms would increase adoption of commercial apps in clinical practice, inform the development of the next generation of apps, and ultimately increase the impact of commercial apps.

Drugs and Medical Devices: Adverse Events and the Impact on Women's Health.

A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women.

Unsuspected Clenbuterol Toxicity in a Patient Using Intramuscular Testosterone.

Clenbuterol is a beta-agonist that has been abused by fitness-oriented individuals for muscle growth and weight loss. We report a case of a 46-year-old man who presented tachycardic, hypokalemic, and hyperglycemic after injecting testosterone obtained from Brazil. He developed refractory hypotension and was started on an esmolol infusion for suspected beta-agonist toxicity. Laboratory analysis showed a detectable clenbuterol serum concentration. Analysis of an unopened ampule contained boldenone undecylenate, clenbuterol, and vitamin E. This case illustrates a novel exposure that caused beta-agonist toxicity and was treated successfully with rapid-onset beta blocker.

False-negative chest radiographs in emergency department diagnosis of pneumonia.

BACKGROUND: Emergency department (ED) patients frequently undergo chest x-ray (CXR) to evaluate for pneumonia. The rate of false-negative CXR in patients with pneumonia is unclear. OBJECTIVES: Identify patients admitted with pneumonia who were diagnosed by CT despite nondiagnostic CXR. METHODS: Retrospective analysis of quality improvement data on adult ED patients admitted with pneumonia over 21 months. Primary outcome was percent of patients diagnosed by CT despite normal CXR. Patients were classified as CXR-diagnosed if they had CXR and no CT, or if antibiotics were ordered after CXR and before CT. CT-based diagnosis was indicated by administration of antibiotics only after CT was completed. RESULTS: 49 patients (11.4%) were diagnosed by CT (p<0.001). These patients were younger (p<0.001) and more often complained of chest pain (p<0.001). CONCLUSIONS: Patients with pneumonia may present with normal or nondiagnostic CXR, although false negatives may be less common than previously reported.

Central respiratory failure during acute organophosphate poisoning.

Organophosphate (OP) pesticide poisoning is a global health problem with over 250,000 deaths per year. OPs affect neuronal signaling through acetylcholine (Ach) neurotransmission via inhibition of acetylcholinesterase (AChE), leading to accumulation of Ach at the synaptic cleft and excessive stimulation at post-synaptic receptors. Mortality due to OP agents is attributed to respiratory dysfunction, including central apnea. Cholinergic circuits are integral to many aspects of the central control of respiration, however it is unclear which mechanisms predominate during acute OP intoxication. A more complete understanding of the cholinergic aspects of both respiratory control as well as neural modification of pulmonary function is needed to better understand OP-induced respiratory dysfunction. In this article, we review the physiologic mechanisms of acute OP exposure in the context of the known cholinergic contributions to the central control of respiration. We also discuss the potential central cholinergic contributions to the known peripheral physiologic effects of OP intoxication.

Tension pneumoperitoneum during routine colonoscopy.

Colonoscopy is generally a safe and effective means to detect, diagnose, and treat colonic abnormalities. Although the overall complication rate is low, the morbidity and mortality following perforation approach 50%. Here we present a case of a 49-year-old woman undergoing routine colonoscopy when she suffered bowel perforation and tension pneumoperitoneum. This is a seldom occurrence and may result following bowel perforation with the rapid accumulation of free air into the peritoneal cavity. It is a life-threatening complication and a surgical emergency.

Expression of the NF-kappaB-responsive gene BTG2 is aberrantly regulated in breast cancer.

BTG2, a p53-inducible antiproliferative gene, is stimulated in breast cancer cells by activation of nuclear factor kappa B (NF-kappaB). In rat mammary glands, BTG2 is expressed in epithelial cells and levels decreased during pregnancy and lactation but recovered during involution. Estrogen and progestin suppress BTG2 expression, suggesting that these steroids, which stimulate proliferation and lobuloalveolar development of mammary epithelial cells, may downregulate BTG2 in the mammary gland during pregnancy. Consistent with the report that BTG2 inhibits cyclin D1 expression, suppression of BTG2 mRNA in the mammary gland during gestation, and by estrogen and progestin, correlated with stimulation of cyclin D1. Ectopic expression of BTG2 inhibited breast cancer cell growth by arresting cells in the G1 phase, an effect reversed by cyclin D1. BTG2 expression was very low or undetectable in human breast cancer cell lines compared with nontumorigenic mammary epithelial cells, and nuclear expression of BTG2 was absent in 65% of human breast tumors compared with adjacent matched normal glands. Spontaneous mammary tumors arising in a mouse model with targeted expression of the early region of the SV40 large tumor Ag demonstrated loss of BTG2 protein very early during the tumorigenic process. Thus deregulation of BTG2 may be an important step in the development of mammary tumors.

Mutually antagonistic effects of androgen and activin in the regulation of prostate cancer cell growth.

Activin, a member of the TGFbeta superfamily, is expressed in the prostate and inhibits growth. We demonstrate that the effects of activin and androgen on regulation of prostate cancer cell growth are mutually antagonistic. In the absence of androgen, activin induced apoptosis in the androgen-dependent human prostate cancer cell line LNCaP, an effect suppressed by androgen administration. Although activin by itself did not alter the cell cycle distribution, it potently suppressed androgen- induced progression of cells into S-phase of the cell cycle and thus inhibited androgen-stimulated growth of LNCaP cells. Expression changes in cell cycle regulatory proteins such as Rb, E2F-1, and p27 demonstrated a strong correlation with the mutually antagonistic growth regulatory effects of activin and androgen. The inhibitory effect of activin on growth was independent of serine, serine, valine, serine motif phosphorylation of Smad3. Despite their antagonistic effect on growth, activin and androgen costimulated the expression of prostate-specific antigen through a Smad3-mediated mechanism. These observations indicate the existence of a complex cross talk between activin and androgen signaling in regulation of gene expression and growth of the prostate.

Mullerian Inhibiting Substance induces NFkB signaling in breast and prostate cancer cells.

The MIS type II receptor is expressed at high levels in the Mullerian duct and in Sertoli cells and granulosa cells of the embryonic and adult gonads. The presence of MIS type II and type I receptors in tissues and cell lines derived from breast and prostate suggests that the prostate and mammary glands may be additional targets for MIS action. In both breast and prostate cancer cells, MIS activated NFkB DNA binding activity and induced IEX-1, an immediate early gene which regulates cell growth and apoptosis. Exposure of cells to MIS inhibited growth by increasing the fraction of cells in the G1 phase of the cell cycle and by inducing apoptosis. These results suggest that MIS may be a putative mediator of growth regulatory signals in the breast and prostate.

Mullerian inhibiting substance promotes interferon gamma-induced gene expression and apoptosis in breast cancer cells.

This report demonstrates that in addition to interferons and cytokines, members of the TGF beta superfamily such as Mullerian inhibiting substance (MIS) and activin A also regulate IRF-1 expression. MIS induced IRF-1 expression in the mammary glands of mice in vivo and in breast cancer cells in vitro and stimulation of IRF-1 by MIS was dependent on activation of the NF kappa B pathway. In the rat mammary gland, IRF-1 expression gradually decreased during pregnancy and lactation but increased at involution. In breast cancer, the IRF-1 protein was absent in 13% of tumors tested compared with matched normal glands. Consistent with its growth suppressive activity, expression of IRF-1 in breast cancer cells induced apoptosis. Treatment of breast cancer cells with MIS and interferon gamma (IFN-gamma) co-stimulated IRF-1 and CEACAM1 expression and synergistic induction of CEACAM1 by a combination of MIS and IFN-gamma was impaired by antisense IRF-1 expression. Furthermore, a combination of IFN-gamma and MIS inhibited the growth of breast cancer cells to a greater extent than either one alone. Both reagents alone significantly decreased the fraction of cells in the S-phase of the cell cycle, an effect not enhanced when they were used in combination. However, MIS promoted IFN-gamma-induced apoptosis demonstrating a functional interaction between these two classes of signaling molecules in regulation of breast cancer cell growth.

Mullerian-inhibiting substance regulates NF-kappa B signaling in the prostate in vitro and in vivo.

Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor beta superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes restricted to the most caudal ends that fuse to form the prostatic utricle. In this article, we have demonstrated MIS type II receptor expression in the normal prostate, human prostate cancer cell lines, and tissue derived from patients with prostate adenocarcinomas. MIS induced NF-kappaB DNA binding activity and selectively up-regulated the immediate early gene IEX-1S in both androgen-dependent and independent human prostate cancer cells in vitro. Dominant negative IkappaBalpha expression ablated both MIS-induced increase of IEX-1S mRNA and inhibition of growth, indicating that activation of NF-kappaB signaling was required for these processes. Androgen also induced NF-kappaB DNA binding activity in prostate cancer cells but without induction of IEX-1S mRNA, suggesting that MIS-mediated increase in IEX-1S was independent of androgen-mediated signaling. Administration of MIS to male mice induced IEX-1S mRNA in the prostate in vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF-kappaB signaling and growth in the prostate gland.