Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill.

Background: In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis. Summary: Current research into CBD-derived cannabinoids is mainly limited to Δ8-tetrahydrocannabinol (Δ8-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of Δ8-THC or Δ9-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than Δ9-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field. Key Messages: The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic.

Treatment Utilization Pattern of Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The aim of this study was to identify patterns of ADHD care, including factors that guide selection and sequencing of treatments in a large nationwide sample of preschool-aged youth over the past 6 years. METHOD: A retrospective cohort study utilizing a large electronic health record (TriNetX) of nearly 24,000 children ages 3 to 6 diagnosed with ADHD. RESULTS: One in three preschoolers with ADHD were prescribed psychotropic medication, most commonly methylphenidate and guanfacine. One in 10 had at least one psychotherapy billing code during the entire assessment with most youth starting medication before psychotherapy. Rates of most treatments, including polypharmacy, increased with comorbid psychiatric disorders or sleep problems and over the course of the coronavirus pandemic. CONCLUSION: Rates of treatment have increased over time but are still largely inconsistent with published care guidelines that advise therapy before medication. Clinicians appear to prioritize psychiatric comorbidity and sleep problems when selecting treatments.

Offering recovery rather than punishment: Implementation of a law enforcement-led pre-arrest diversion-to-treatment program for adults with substance use disorders.

BACKGROUND: The opioid epidemic has strained the US criminal justice system. Law enforcement frequently encounters persons with substance use disorder (SUD). Law enforcement-led, pre-arrest diversion programs linking individuals with SUD to addiction treatment instead of arrest and prosecution has the potential to reduce crime, overdoses, and other community harms. We implemented a pre-arrest diversion-to-treatment program-the Madison Addiction Recovery Initiative (MARI)-from September 2017 to August 2020, and describe the key components of MARI's effective implementation. METHODS: Adults who committed an eligible, drug use-related crime were offered a 6-month MARI participation with referral to treatment in lieu of arrest; criminal charges for that crime were "voided" upon the successful MARI completion. Formative evaluation, with stakeholder feedback and team meeting minutes, assessed key factors influencing implementation. Process evaluation consisted of tracking participant referrals, enrollment, and engagement. Police officers, MARI participants, and treatment center staff members were surveyed about program experiences and attitudes. The study used descriptive statistics to describe quantitative survey responses; thematic qualitative analysis identified major themes in qualitative responses. RESULTS: Of 263 participants, 160 initiated program engagement, with 100 successfully completing MARI. Interim evaluations and community partner feedback informed program protocol adjustments to increase participant enrollment, retention and diversity, streamline the referral processes, and transition to telehealth during the COVID-19 pandemic. CONCLUSION: Rigorous evaluation and community partner feedback are essential components of effective implementation and sustainability of a law enforcement-led pre-arrest diversion-to-treatment program, which has the potential to both reduce crime and overdose, and change the lives of people with SUD.

Micro-doppler radar to evaluate risk for musculoskeletal injury: Protocol for a case-control study with gold standard comparison.

BACKGROUND: Beyond causing significant morbidity and cost, musculoskeletal injuries (MSKI) are among the most common reasons for primary care visits. A validated injury risk assessment tool for MSKI is conspicuously absent from current care. While motion capture (MC) systems are the current gold standard for assessing human motion, their disadvantages include large size, non-portability, high cost, and limited spatial resolution. As an alternative we introduce the Micro Doppler Radar (MDR); in contrast with MC, it is small, portable, inexpensive, and has superior spatial resolution capabilities. While Phase 1 testing has confirmed that MDR can identify individuals at high risk for MSKI, Phase 2 testing is still needed. Our aims are to 1) Use MDR technology and MC to identify individuals at high-risk for MSKI 2) Evaluate whether MDR has diagnostic accuracy superior to MC 3) Develop MDR algorithms that enhance accuracy and enable automation. METHODS AND FINDINGS: A case control study will compare the movement patterns of 125 ACL reconstruction patients to 125 healthy controls. This study was reviewed and approved by the Pennsylvania State University Human Research Protection Program (HRPP) on May 18, 2022, and the IRB approval number is STUDY00020118. The ACL group is used as a model for a "high risk" population as up to 24% will have a repeat surgery within 2 years. An 8-camera Motion Analysis MC system with Cortex 8 software to collect MC data. Components for the radar technology will be purchased, assembled, and packaged. A micro-doppler signature projection algorithm will determine correct classification of ACL versus healthy control. Our previously tested algorithm for processing the MDR data will be used to identify the two groups. Discrimination, sensitivity and specificity will be calculated to compare the accuracy of MDR to MC in identifying the two groups. CONCLUSIONS: We describe the rationale and methodology of a case-control study using novel MDR technology to detect individuals at high-risk for MSKI. We expect this novel approach to exhibit superior accuracy than the current gold standard. Future translational studies will determine utility in the context of clinical primary care.

Potential problems and solutions of opioid-based treatment in neonatal opioid withdrawal syndrome (NOWS): a scoping review protocol.

INTRODUCTION: Rates of neonatal opioid withdrawal syndrome (NOWS) have paralleled the rise of opioid use during pregnancy. While short-term phenotypic symptoms of NOWS are well defined, molecular implications and long-term effects are not well understood. Preferred and first-line of treatment for NOWS includes non-pharmacological interventions; however, more than half of the NOWS neonates will need pharmacologics, with opioids as the primary pharmacological treatment. While effective at reducing symptoms, treating NOWS with opioids is paradoxical given that molecular and long-term developmental consequences with such exposure are unknown. There is a pressing need for a synthesis of current and potential/ novel treatment options for NOWS. METHODS AND ANALYSIS: Following a published framework, a scoping review will be conducted to evaluate NOWS treatment, including established treatment methods and novel methods that may warrant future research and consideration. Using broad search terms, as well as Medical Subject Headings terms, a comprehensive search of PubMed, Cochrane Library, Google Scholar, CINAHL, Web of Science and Scopus, as well as references of selected literature, will take place, followed by a screening procedure to identify included and excluded articles. Included studies must address NOWS treatment, or opioid withdrawal treatment of any age group, that may or may not have been tested in preclinical or clinical models. Results will summarise the current pharmacological and non-pharmacological treatment methods for NOWS, as well as potential novel treatments with a specific interest in non-opioid pharmacological interventions. ETHICS AND DISSEMINATION: This scoping review aims to broadly search preclinical and clinical literature as it relates to treatment of NOWS, including potential novel treatments with a specific interest in non-opioid pharmacological interventions. Given that this study does not directly involve human subjects or animal subjects research, Institutional Review Board (IRB) or Institutional Animal Care and Use Committee (IACUC) approval is not required. Results of this scoping review will be disseminated at conferences and submitted for publication in a peer-reviewed journal.

Dose titration with the glucagon-like peptide-1 agonist, liraglutide, reduces cue- and drug-induced heroin seeking in high drug-taking rats.

Opioid use disorder (OUD), like other substance use disorders (SUDs), is widely understood to be a disorder of persistent relapse. Despite the use of three FDA-approved medications for OUD, typically in conjunction with behavioral treatments, relapse rates remain unacceptably high. Whereas medication assisted therapy (MAT) reduces the risk of opioid overdose mortality, the benefits of MAT are negated when people discontinue the medications. Currently approved medications present barriers to efficient use, including daily visits to a treatment center or work restrictions. With spiking increases in opioid relapse and death, it is imperative to identify new treatments that can reduce the risk of relapse. Recent evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently FDA-approved to treat obesity and type two diabetes, may be promising candidates to reduce relapse. GLP-1RAs have been shown to reduce relapse in rats, whether elicited by cues, drug, and/or stress. However, GLP-1RAs also can cause gastrointestinal malaise, and therefore, in humans, the medication typically is titrated up to full dose when initiating treatment. Here, we used a rodent model to test whether cue- and drug-induced heroin seeking can be reduced by the GLP-1RA, liraglutide, when the dose is titrated across the abstinence period and prior to test. The results show this titration regimen is effective in reducing both cue-induced heroin seeking and drug-induced reinstatement of heroin seeking, particularly in rats with a history of high drug-taking. Importantly, this treatment regimen had no effect on either circulating glucose or insulin. GLP-1RAs, then, appear strong candidates for the non-opioid prevention of relapse to opioids.

Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats.

Substance use disorder is challenging to treat due to its relapsing nature. In the last decade, opioid use disorder has been a threat to public health, being declared an epidemic by the Centers for Disease Control and Prevention. This is a tragic situation, considering there currently are only three effective, yet not ideal, treatments to prevent relapse to opioids. Recent research has shown that hormones that modulate hunger and satiety also can modulate motivated behavior for drugs of abuse. For example, the short-acting analog of glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates homeostatic feeding, has been shown to reduce responding for rewarding stimuli such as food, cocaine, heroin, and nicotine when administered over several days or weeks. This may serve as an effective adjuvant during treatment; however, whether it would be effective when used acutely to bridge a patient between cessation of use and onset of medication for the treatment of an opioid addiction is unknown. Here, we tested the acute effects of the longer acting GLP-1 analog, liraglutide, on heroin-seeking. In rats with heroin self-administration experience, we found that subcutaneous administration of an acute dose of 0.3-mg/kg liraglutide was effective in preventing drug-seeking after exposure to three major precipitators: drug-associated cues, stress (yohimbine-induced), and the drug itself. Finally, we confirmed that the reduction in drug-seeking is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. As such, acute use of GLP-1 analogs may serve as a new and effective nonopioid bridge to treatment.

The relationship between police contacts for drug use-related crime and future arrests, incarceration, and overdoses: a retrospective observational study highlighting the need to break the vicious cycle.

BACKGROUND: Individuals with substance use disorder often encounter law enforcement due to drug use-related criminal activity. Traditional policing approaches may not be effective for reducing recidivism and improving outcomes in this population. Here, we describe the impact of traditional policing approach to drug use-related crime on future recidivism, incarceration, and overdoses. METHODS: Using a local Police Department (PD) database, we identified individuals with a police contact with probable cause to arrest for a drug use-related crime ("index contact"), including for an opioid-related overdose, between September 1, 2015, and August 31, 2016 (Group 1, N = 52). Data on police contacts, arrests, and incarceration 12 months before and after the index contact were extracted and compared using Fisher's exact or Wilcoxon signed-rank tests. County-level data on fatal overdoses and estimates of time spent by PD officers in index contact-related responses were also collected. To determine whether crime-related outcomes changed over time, we identified a second group (Group 2, N = 263) whose index contact occurred between September 1, 2017, and August 31, 2020, and extracted data on police contacts, arrests, and incarceration during the 12 months prior to their index contact. Pre-index contact data between Groups 1 and 2 were compared with Fisher's exact or Mann-Whitney U tests. RESULTS: Comparison of data during 12 months before and 12 months after the index contact showed Group 1 increased their total number of overdose-related police contacts (6 versus 18; p = 0.024), incarceration rate (51.9% versus 84.6%; p = 0.001), and average incarceration duration per person (16.2 [SD = 38.6] to 50 days [SD = 72]; p < 0.001). In the six years following the index contact, 9.6% sustained a fatal opioid-related overdose. For Group 1, an average of 4.7 officers were involved, devoting an average total of 7.2 h per index contact. Comparison of pre-index contact data between Groups 1 and 2 showed similar rates of overdose-related police contacts and arrests. CONCLUSIONS: The results indicated that the traditional policing approach to drug use-related crime did not reduce arrests or incarceration and was associated with a risk of future overdose fatalities. Alternative law enforcement-led strategies, e.g., pre-arrest diversion-to-treatment programs, are urgently needed.

Attachment Style and Burn Pain.

Pain management is a challenge when treating patients with burn injuries. Understanding the behavioral and interpersonal aspects of the experience of burn pain may aid in its management. Attachment style-which influences how an individual relates to other people-is one aspect that may affect the experience of burn pain. Past research has shown a relationship between an individual's attachment style and certain types of pain and disorders. The study builds upon that past work to investigate specifically how attachment style affects the experience of acute burn pain. Participants were at least 18 years old and admitted to an American Burn Association verified burn center with burns encompassing 30% or less TBSA. Participants completed demographic questionnaires and a standardized measure of adult attachment style. Data regarding use of analgesics, daily pain scores, and burn-related information were collected through medical chart review. Participants who reported a secure attachment style required less pain medication and reported less pain compared with participants who reported an insecure attachment style. There was no difference in burn-related variables between participants with secure and insecure attachment styles, suggesting that these differences were not due to burn-related factors. Attachment, therefore, may play a role in an individual's perception of acute burn pain, which impacts analgesic requirements needed to manage the pain. These results have potential implications for the use of psychosocial interventions to reduce the experience of pain and the amount of pain medication needed to manage acute burn pain.

Glucagon-like peptide-1 receptor agonist, liraglutide, reduces heroin self-administration and drug-induced reinstatement of heroin-seeking behaviour in rats.

Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP-1 analogue, liraglutide (LIR), in reducing heroin addiction-like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self-administration, prevents escalation of heroin self-administration and reduces drug-induced reinstatement of heroin-seeking behaviour in rats. A 1-h pretreatment time, however, was too short to reduce cue-induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR-paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin-naïve or heroin-experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.

Diabetes, Drug Treatment, and Mortality in COVID-19: A Multinational Retrospective Cohort Study.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe coronavirus disease 2019 (COVID-19) outcomes possibly because of dysregulated inflammatory responses. Glucose-regulating medications, such as glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and pioglitazone, are known to have anti-inflammatory effects that may improve outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 56 large health care organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days after a COVID-19 diagnosis. After matching for age, sex, race, ethnicity, BMI, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions (GLP-1R: 15.7% vs. 23.5%, risk ratio [RR] 0.67 [95% CI 0.57-0.79; P < 0.001]; pioglitazone: 20.0% vs. 28.2%; RR 0.71 [95% CI 0.54-0.93; P = 0.01]). Use of GLP-1R agonists was also associated with reductions in respiratory complications (15.3% vs. 24.9%, RR 0.62 [95% CI 0.52-0.73]; P < 0.001) and incidence of mortality (1.9% vs. 3.3%, RR 0.58 [95% CI 0.35-0.97]; P = 0.04). Use of DPP-4 inhibitors was associated with a reduction in respiratory complications (24.0% vs. 29.2%, RR 0.82 [95% CI 0.74-0.90]; P < 0.001), and continued use of DPP-4 inhibitors after hospitalization was associated with a decrease in mortality compared with those who discontinued use (9% vs. 19%, RR 0.45 [95% CI 0.28-0.72]; P < 0.001). In conclusion, use of glucose-regulating medications, such as GLP-1R agonists, DPP-4 inhibitors, or pioglitazone, may improve COVID-19 outcomes for patients with T2DM; randomized clinical trials are needed to further investigate this possibility.

Multisite 11-year experience of less-intensive vs intensive therapies in acute myeloid leukemia.

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Vagotomy increases alcohol intake in female rats in diet dependent manner: Implications for increased alcohol use disorder after roux-en-y gastric bypass surgery.

A variety of weight loss surgeries have been developed to fight the obesity epidemic, with Roux-en-Y gastric bypass (RYGB) being one of the most effective and popular procedures. However, the underlying mechanisms behind its efficacy are still not well understood. Furthermore, growing clinical evidence suggests that RYGB may result in increased risk for development of alcohol use disorder (AUD). The vagus nerve is a potentially critical contributor to increased risk of AUD following RYGB due to the potential for significant damage to the vagus during surgery, which has been confirmed in rodent studies. Studies aiming at the mechanisms underlying development of alcohol or substance use disorders following the surgery have exclusively used male rats, despite the majority of RYGB patients being female. Thus, the current study had two objectives: 1) to investigate the effect of RYGB on ethanol (EtOH) intake in female rats using a protocol previously established in male rats, and 2) to test the effect of vagal damage and high fat diet (HFD) on EtOH intake in female rats. In the first study, 22 female rats were maintained on HFD for four weeks and then split into two surgical groups, RYGB (n = 10) and Sham (n = 12). All rats then underwent a two-bottle choice test of increasing EtOH concentrations: 2%, 4%, 6%, 8%. Rats were then forced to abstain from EtOH for two weeks, after which access to 8% EtOH was reinstated. The RYGB female rats significantly increased their intake for low concentrations of EtOH (2% and 4%) and during the reinstatement period for 8%. These results mirror those seen in male rats, and thus, confirms RYGB in female rats as an equally viable model to males. In the second study, 40 female rats were separated into four groups: HFD/Sham, HFD/Vagotomy, normal diet (ND)/Sham, and ND/Vagotomy. All rats then were subjected to the same two-bottle choice test protocol as in the previous study. Rats in the vagotomy condition had significantly greater preference for 2% and 4% EtOH compared with Sham-operated controls. EtOH intake, either in ml or adjusted for body weight, was greater in rats maintained on ND compared with rats maintained on HFD. These data suggest that vagal damage may, at least in part, contribute to increased preference for EtOH. Furthermore, this increase in EtOH preference is counter to the blunting effect of HFD. In conclusion, the data presented here suggest a role for vagal damage in risk of AUD after weight loss surgery.

Rabies Vaccination Compliance and Reasons for Incompletion.

INTRODUCTION: Rabies is a fatal disease with a 91% mortality rate in the United States. Current treatment of rabies consists of post-exposure prophylaxis treatment involving a complicated vaccination regimen. Studies conducted in other countries have found that patients do not complete their rabies vaccination treatment due to forgetting about their treatment, lack of time for visits, and the financial burden of treatment. However, little is known about why patients do not complete the rabies series in the US. The objective of this study was to determine the reasons why patients in the US do not complete rabies treatment. METHODS: We performed a retrospective study to evaluate rabies post-exposure prophylaxis completion in the emergency department of an academic suburban hospital between June 2014- July 2017. Further review was performed for patients who received inadequate vaccination to determine the cause of treatment incompletion. We conducted additional follow-up by phone survey for those patients who did not complete their rabies treatment but had no explanation for discontinuation available in the medical chart review. RESULTS: Results indicated 198 patients received rabies post-exposure treatment during the inclusion period. Of these, 145 patients completed the rabies vaccination regimen. Reasons for treatment incompletion were found for 29 patients, and 24 patients were lost to follow-up. Of the 29 patients for which discontinuation was assessed, 23 patients (79.3%) stopped treatment due to appropriate reasons - either the animal involved tested negative for the rabies virus or the patient had prior rabies treatment and only required two booster shots. Reasons for not completing the series when medically indicated included the patient deciding to not return for treatment, lack of awareness of the full vaccination regimen, and the patient declining initiation of rabies vaccination. CONCLUSION: Most patients in the US discontinue their rabies vaccination treatment for appropriate reasons; however, there is a proportion of patients who discontinue rabies vaccination when further treatment is medically indicated. This subset of patients is particularly at risk of rabies-related mortality, and additional measures need to be taken to ensure increased treatment compliance.

Regimen-intensity per count-recovery and hospitalization index: A new tool to assign regimen intensity for AML.

BACKGROUND: Low-intensity regimens have been increasingly used to treat older patients with acute myeloid leukemia (AML). Recent studies, however, suggest older patients can tolerate and potentially benefit from intensive chemotherapeutic regimens. The ability to compare the utility of varying regimen intensities in AML is hindered by the lack of a standardized definition of "regimen intensity." METHODS: We conducted a survey asking AML physicians which of 38 regimens they would consider intensive vs less-intensive. Electronic medical records of 592 patients receiving many of these regimens were used to design a model characterizing regimens as intensive vs less-intensive as identified by ≥75% physician consensus. Variables included frequency and length of hospitalizations, intensive care unit admissions, severe gastrointestinal toxicities, time to nadir, and recovery of neutrophil/platelet count. RESULTS: Physicians agreed at a rate of 75%-100% on the assignment of degree of intensity to the majority (n = 28) of these regimens, while the level of agreement was <75% for the remaining 10 regimens (26%). Logistic regression analyses identified number and length of hospitalizations to be significantly associated with intensive regimens and count recovery with less-intensive regimens. We created the "regimen-intensity per count-recovery and hospitalization" (RICH) index with an AUC of 0.87. Independent model validation yielded an AUC of 0.75. CONCLUSIONS: We were able to generate a novel model that defines regimen intensity for many therapies used to treat AML. Results facilitate a future randomized study comparing intensive vs less-intensive regimens.

Analgesic use in contemporary burn practice: Applications to burn mass casualty incident planning.

BACKGROUND: Determining the amount of analgesics required will help burn centers improve their ability to plan for a burn mass casualty incident (BMCI). We sought to quantify the amount of analgesics needed in an inpatient burn population. We hoped that assessing the analgesic use in daily burn care practice will potentially help estimate opioid needs in a burn mass casualty incident (BMCI). METHODS: We included patients with burns covering equal to or less than 30% total body surface area (TBSA), admitted from spring 2013 to spring 2015. Patient records were reviewed for analgesics and adjuncts, pain scores, age and TBSA. The doses of the different opioids administered were converted into morphine equivalent doses (MED). RESULTS: We enrolled 141 acute burn survivors with a mean TBSA of 8.2±0.6%. The lowest daily average MED per person was 24.6±2.0mg MED, recorded on the day of injury. The daily average MED per person increased until it peaked at 52.5±5.6mg MED at day 8 post-burn. Then, it declined to 24.6±3.4mg MED by day 14. Bivariate regression analysis of average MED by TBSA showed a significant positive correlation (p<0.001). The analysis of average MED by age showed a significant negative correlation (p<0001). CONCLUSION: Our study quantified opioid requirements in an inpatient burn population and identified TBSA (positively) and age (negatively) as significant predictors.

Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams.

Evidence indicates that obesity can be promoted by chemical 'obesogens' that drive adiposity, hunger, inflammation and suppress metabolism. Dioctyl sodium sulfosuccinate (DOSS), a lipid emulsifier and candidate obesogen in vitro, is widely used in processed foods, cosmetics and as stool softener medicines commonly used during pregnancy. In vivo testing of DOSS was performed in a developmental origins of adult obesity model. Pregnant mice were orally administered vehicle control or DOSS at times and doses comparable to stool softener use during human pregnancy. All weaned offspring consumed only standard diet. Adult male but not female offspring of DOSS-treated dams showed significantly increased body mass, overall and visceral fat masses, and decreased bone area. They exhibited significant decreases in plasma adiponectin and increases in leptin, glucose intolerance and hyperinsulinemia. Inflammatory IL-6 was elevated, as was adipose Cox2 and Nox4 gene expressions, which may be associated with promoter DNA methylation changes. Multiple significant phospholipid/sterol lipid increases paralleled profiles from long-term high-fat diet induced obesity in males. Collectively, developmental DOSS exposure leads to increased adult adiposity, inflammation, metabolic disorder and dyslipidemia in offspring fed a standard diet, suggesting that pharmaceutical and other sources of DOSS taken during human pregnancy might contribute to long-term obesity-related health concerns in offspring.

U.S. Soldiers and Foreign Language School: Stressors and Health.

INTRODUCTION: While previous studies have examined the stress of the military training environment, studies have not systematically examined the stress associated with attending the Defense Language Institute Foreign Language Center (DLIFLC). Service members assigned to DLIFLC endure intense academic pressure to succeed while meeting military requirements. Thus, not only are traditional academic stressors likely to be of concern but there are other academic and military-related stressors that have to managed by students. The goal of the present study was to characterize the stressors facing military students, document their mental health status and well-being, and identify mitigating factors such as coping, social support, time management, and the classroom environment. MATERIALS AND METHODS: Data were obtained from a cross-sectional survey administered in March of 2016. Study participants were 759 active-duty U.S. soldiers enrolled in DLIFLC, with a consent rate of 87.7%. Surveys were administered in classroom settings. Survey topics included demographics, student experience (e.g., classroom hours, stressors), mental health (e.g., depression, anxiety, hazardous alcohol use) and burnout, and mitigating factors (e.g., coping, social support, time management, classroom environment). Multiple logistic regressions were used to identify which variables in the predictor set were significantly associated with each of the five outcomes while controlling for the presence of all other variables. RESULTS: In terms of behavioral health, 7.2% met screening criteria for depression, 9.4% for anxiety, and 17.1% for hazardous alcohol use; 43.4% reported high/very high levels of burnout. About one-third of the sample who had taken a test failed at least one (32.2%). In terms of common stressors more than half reported high or very high-stress levels from meeting academic expectations, not getting enough sleep, and pressure to succeed from civilian language instructors. For depression and anxiety, regression results found that denial coping was a risk factor whereas positive social interaction and classroom climate were protective factors. For hazardous alcohol use, denial coping and higher rank were risk factors and acceptance and time management were protective factors. In terms of academic burnout, in-class and military work hours were risk factors, whereas time management and classroom climate were protective. Finally, lower educational attainment, time spent in the classroom and times spent on military duties predicted exam failure. CONCLUSION: Individual coping, social connection, and classroom climate are each associated with better DLIFLC student adjustment. Denial coping appears to impede individuals from assembling the personal resources needed to study a foreign language. In contrast, acceptance appears to support healthier adjustment, perhaps freeing individuals to focus on the task at hand rather than expend valuable energy resisting the demands being placed on them. Positive social interaction also appears to provide an important resource for students, and positive classroom climate is also associated with better mental health. These findings suggest that there are measures that individuals and the school can take to improve the DLIFLC experience and support students as they manage a myriad of stressors given the significance of their success to individual students and to the larger organization.