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INTRODUCTION: There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores. METHODS: Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC). RESULTS: 90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion. CONCLUSION: Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy). METHODS: Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination. RESULTS: There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedges g= .45). Changes in DUDIT scores were not significantly different between treatment groups. CONCLUSIONS: MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD.

INTRODUCTION: 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning. The acute administration of MDMA in healthy controls modifies recruitment of brain regions involved in the hyperactive fear response in PTSD such as the amygdala, hippocampus, and insula. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients. METHODS: We analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory (trauma and neutral) response before and two-months after MDMA-AT in nine veterans and first-responders with chronic PTSD of 6 months or more. RESULTS: We hypothesized that MDMA-AT would increase amygdala-hippocampus resting-state functional connectivity, however we only found evidence of a trend in the left amygdala-left hippocampus (t = -2.91, uncorrected p = 0.0225, corrected p = 0.0901). We also found reduced activation contrast (trauma > neutral) after MDMA-AT in the cuneus. Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala-left posterior cingulate cortex (PCC), left amygdala-right PCC, left amygdala-left insula, and left isthmus cingulate-left posterior hippocampus. DISCUSSION: Amygdala-insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration. These findings compliment previous research indicating that amygdala, hippocampus, and insula functional connectivity is a potential target of MDMA-AT, and highlights other regions of interest related to memory processes. More research is necessary to determine if these findings are specific to MDMA-AT compared to other types of treatment for PTSD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02102802, identifier NCT02102802.

BackgroundFor young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.MethodsWe did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.FindingsBetween Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to

E-cigarettes are promoted as healthier alternatives to conventional cigarettes. Many cigarette smokers use both products. It is unknown whether the additional use of e-cigarettes among cigarette smokers (dual users) is associated with reduced exposure to tobacco-related health risks. Cross-sectional analysis was performed using baseline data from the Health eHeart Study, among English-speaking adults, mostly from the United States. Cigarette use (# cigarettes/day) and/or e-cigarette use (# days, # cartridges, and # puffs) were compared between cigarette only users vs. dual users. Additionally, we examined cardiopulmonary symptoms/ conditions across product use: no product (neither), e-cigarettes only, cigarettes only, and dual use. Among 39,747 participants, 573 (1.4%) reported e-cigarette only use, 1,693 (4.3%) reported cigarette only use, and 514 (1.3%) dual use. Dual users, compared to cigarette only users, reported a greater median (IQR) number of cigarettes per day, 10.0 (4.0-20.0) vs. 9.0 (3.0-15.0) (p < .0001), a lower (worse) median (IQR) SF-12 general health score, 3.3 (2.8-3.8) vs. 3.5 (2.8-3.9) (p = .0014), and a higher (worse) median (IQR) breathing difficulty score in the past month, 2.0 (1.0-2.0) vs. 1.0 (1.0-2.0) (p = .001). Of the 19 cardiopulmonary symptoms/ conditions, having a history of arrhythmia was significantly different between cigarette only users (14.2%) and dual users (17.8%) (p = .02). In this sample, dual use was not associated with reduced exposure to either (i) cigarettes, compared to cigarette only users or (ii) e-cigarettes, compared to e-cigarette only users. E-cigarette only use, compared to no product use, was associated with lower general health scores, higher breathing difficulty scores (typically and past month), and greater proportions of those who responded 'yes' to having chest pain, palpitations, coronary heart disease, arrhythmia, COPD, and asthma. These data suggest the added use of e-cigarettes alone may have contributed to cardiopulmonary health risks particularly respiratory health risks.

BackgroundMedical marijuana legalization is associated with a higher prevalence of marijuana use which may affect cigarette use and nicotine dependence in co-users. In the present study, we examined relationships between statewide legalization of medical marijuana and prevalence of cigarette and marijuana co-use and nicotine dependence in co-using adolescents and adults.MethodsData were analyzed from the 2013 National Survey on Drug Use and Health. We compared cigarette and marijuana co-use in the past 30days across age categories (12-64 years) by statewide medical marijuana legalization. Logistic regression models were used to estimate the odds of having nicotine dependence among current cigarette smokers who also reported past 30-day marijuana use and "ever but not current" marijuana use (vs. "never" use) adjusting for covariates including statewide legalization of medical marijuana.ResultsOverall, 5.1% of the sample reported past 30-day cigarette and marijuana co-use and a higher proportion of co-users resided in states where medical marijuana was legal compared to illegal (5.8% vs. 4.8%; p=0.0011). Co-use was associated with greater odds of having nicotine dependence compared to cigarette-only use across age categories. Odds were highest and up to 3-times higher in adolescents aged 12-17 years (OR=3.54; 95%CI: 1.81-6.92) and adults aged 50-64 years (OR=3.08; CI: 1.45-6.55).ConclusionMarijuana policy could inadvertently affect cigarette and marijuana co-use and pose challenges to tobacco cessation.

BackgroundAs wearable sensors/devices become increasingly popular to promote physical activity (PA), research is needed to examine how and which components of these devices people use to increase their PA levels.Aims(1) To assess usability and level of engagement with the Fitbit One and daily SMS-based prompts in a 6-week PA intervention, and (2) to examine whether use/ level of engagement with specific intervention components were associated with PA change.MethodsData were analyzed from a randomized controlled trial that compared (1) a wearable sensor/ device (Fitbit One) plus SMS-based PA prompts, and (2) Fitbit One only, among overweight/ obese adults (N = 67). We calculated average scores from Likert-type response items that assessed usability and level of engagement with device features (e.g., tracker, website, mobile app, and SMS-based prompts), and assessed whether such factors were associated with change in steps/day (using Actigraph GT3X+).ResultsParticipants reported the Fitbit One was easy to use and the tracker helped to be more active. Those who used the Fitbit mobile app (36%) vs. those who did not (64%) had an increase in steps at 6-week follow-up, even after adjusting for previous web/app use: +545 steps/ day (SE = 265) vs. -28 steps/ day (SE = 242) (p = .04).ConclusionsLevel of engagement with the Fitbit One, particularly the mobile app, was associated with increased steps. Mobile apps can instantly display summaries of PA performance and could optimize self-regulation to activate change. More research is needed to determine whether such modalities might be cost-effective in future intervention research and practice.

ObjectivesWe examined effects of long-term medical marijuana legalization on cigarette co-use in a sample of adults.MethodsWe conducted secondary analysis using data from the 2014 US Tobacco Attitudes and Beliefs Survey, which consisted of cigarette smokers, aged ≥ 45 years (N = 506). Participants were categorized by their state residence, where medical marijuana was (1) illegal, (2) legalized < 10 years, and (3) legalized ≥ 10 years. The Web-based survey assessed participants' marijuana use, beliefs and attitudes on marijuana, and nicotine dependence using Fagerstrom Tolerance for Nicotine Dependence (FTND) and Hooked on Nicotine Checklist (HONC) scores.ResultsIn cigarette smokers aged ≥ 45 years, long-term legalization of medical marijuana was associated with stable positive increases in marijuana use prevalence (ever in a lifetime) (p = .005) and frequency (number of days in past 30 days) (unadjusted p = .005; adjusted p = .08). Those who reported marijuana co-use had greater FTND and HONC scores after adjusting for covariates (p = .05).ConclusionsThese preliminary findings warrant further examination of the potential impact of long-term legalization of medical marijuana on greater cigarette and marijuana co-use in adults and higher nicotine dependence among co-users at the population level.

BackgroundDepressive symptoms can lower adherence and change in dietary studies. Behavioral activation may reduce these effects.PurposeThis study aims to assess relationships among depressive symptoms on adherence and dietary change in the Women's Healthy Eating and Living (WHEL) StudyMethodsSecondary analyses from the WHEL Study, which achieved major dietary change in breast cancer survivors (N = 2817), were conducted. Logistic regressions were undertaken of baseline depressive symptoms (six-item Center for Epidemiologic Studies Depression Scale (CES-D)) with (1) completion of 1- and 4-year study assessments and (2) validated change in dietary behavior in the intervention group.ResultsIn the comparison group (vs. intervention), depressive symptoms lowered completion of dietary recalls and clinic visits [4 years: odds ratio (OR) = 2.0; 95 % confidence interval (CI) = 1.4-3.0]. The behaviorally oriented intervention achieved major change in those furthest from study targets, although changes were lower in those with depressive symptoms: fruit/vegetable (+37.2 %), fiber (+49.0 %), and fat (-22.4 %).ConclusionsBehavioral activation in dietary change interventions can overcome the impact of depressive symptoms.

BackgroundStudies have shown self-monitoring can modify health behaviors, including physical activity (PA). This study tested the utility of a wearable sensor/device (Fitbit(®) One™; Fitbit Inc., San Francisco, CA) and short message service (SMS) text-messaging prompts to increase PA in overweight and obese adults.Materials and methodsSixty-seven adults wore a Fitbit One tracker for 6 weeks; half were randomized to also receive three daily SMS-based PA prompts. The Fitbit One consisted of a wearable tracker for instant feedback on performance and a Web site/mobile application (app) for detailed summaries. Outcome measures were objectively measured steps and minutes of PA by intensity using two accelerometers: Actigraph™ (Pensacola, FL) GT3X+ (primary measure) at baseline and Week 6 and Fitbit One (secondary measure) at baseline and Weeks 1, 2, 3, 4, 5, and 6.ResultsMixed-model repeated-measures analysis of primary measures indicated a significant within-group increase of +4.3 (standard error [SE]=2.0) min/week of moderate- to vigorous-intensity PA (MVPA) at 6-week follow-up (p=0.04) in the comparison group (Fitbit only), but no study group differences across PA levels. Secondary measures indicated the SMS text-messaging effect lasted for only 1 week: the intervention group increased by +1,266 steps (SE=491; p=0.01), +17.8 min/week MVPA (SE=8.5; p=0.04), and +38.3 min/week total PA (SE=15.9; p=0.02) compared with no changes in the comparison group, and these between-group differences were significant for steps (p=0.01), fairly/very active minutes (p

ObjectivesTo describe older smokers' perceptions of risks and use of e-cigarettes, and their responses to marketing and knowledge of, and opinions about, regulation of e-cigarettes.MethodsEight 90-minute focus groups with 8 to 9 participants met in urban and suburban California to discuss topics related to cigarettes and alternative tobacco products.ResultsOlder adults are using e-cigarettes for cessation and as a way to circumvent no-smoking policies; they have false perceptions about the effectiveness and safety of e-cigarettes. They perceive e-cigarette marketing as a way to renormalize smoking.ConclusionsTo stem the current epidemic of nicotine addiction, the FDA must take immediate action because e-cigarette advertising promotes dual use and may contribute to the renormalization of smoking.

Epidemiologic studies have consistently found that self-reported allergies are associated with reduced risk of pancreatic cancer. Our aim was to prospectively assess the relationship between serum immunoglobulin E (IgE), a marker of allergy, and risk. This nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) included subjects enrolled in 1994 to 2001 and followed through 2010. There were 283 cases of pancreatic cancer and 544 controls matched on age, gender, race, and calendar date of blood draw. Using the ImmunoCAP system, we measured total IgE (normal, borderline, elevated), IgE to respiratory allergens, and IgE to food allergens (negative or positive) in serum collected at baseline. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We assessed interactions with age, gender, smoking, body mass index, and time between randomization and case diagnosis. Overall, there was no association between the IgE measures and risk. We found a statistically significant interaction by baseline age: in those aged ≥65 years, elevated risks were observed for borderline total IgE (OR, 1.43; 95% CI, 0.88-2.32) and elevated total IgE (OR, 1.98; 95% CI, 1.16-3.37) and positive IgE to food allergens (OR, 2.83; 95% CI, 1.29-6.20); among participants