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Clinical guidelines currently recommend practitioners titrate stimulant medications, i.e., methylphenidate (MPH) and amphetamines (AMP), to the dose that maximizes symptom control without eliciting intolerable adverse events (AEs) when treating attention-deficit/hyperactivity disorder (ADHD) in school-aged children/adolescents. However, robust evidence-base regarding the effects of doses and dosing strategies of stimulants on clinical outcomes in the treatment of children/adolescents with ADHD is currently lacking and stimulants are often underdosed in clinical practice. To address this gap and provide rigorous evidence-base in relation to the dose and dosing strategy of stimulants, we conducted the largest systematic review and dose–response meta-analysis examining change in ADHD symptoms (efficacy), and treatment discontinuations due to AEs (tolerability) and any reason (acceptability). We conducted one-stage random-effects dose–response meta-analyses examining MPH and AMP separately, stratifying trials based on fixed-dose and flexible-dose design. Daily doses of stimulants were converted to MPH- and AMP-equivalent doses by adjusting for different pharmacokinetics across formulations. We also conducted pairwise meta-analyses to provide indirect comparisons between flexible-dose versus fixed-dose trials. Our study included 65 RCTs involving 7 877 children/adolescents. Meta-analyses of fixed-dose trials for both MPH and AMP demonstrated increased efficacy and increased likelihood of discontinuation due to AEs with increasing doses of stimulants. The incremental benefits of stimulants in terms of efficacy decreased beyond 30 mg of MPH or 20 mg of AMP in fixed-dosed trials. In contrast, meta-analyses of flexible-dose trials for both MPH and AMP demonstrated increased efficacy and reduced likelihood of discontinuations for any reason with increasing stimulant doses. The incremental benefits of stimulants in terms of efficacy remained constant across the FDA-licensed dose range for MPH and AMP in flexible-dose trials. Our results suggest that flexible titration as needed, i.e., considering the presence of ADHD symptoms, and tolerated, i.e., considering the presence of dose-limiting AEs, to higher doses of stimulants is associated with both improved efficacy and acceptability because practitioners can increase/reduce doses based on control of ADHD symptoms/dose-limiting AEs. Although fixed-dose trials that are required by the FDA are valuable to characterize dose-dependency, they may underestimate the true potential benefit of trialing dose-increases of stimulants in clinical practice by not allowing dose adjustment based on response and tolerability. Additional research is required to investigate potential long-term effects of using high doses of stimulants in clinical practice.

The authors sought to identify factors that affect hospital staff's decision to pursue criminal charges against patients who assault staff on inpatient psychiatric units.Data on assaults occurring on inpatient psychiatric units in one hospital system were collected over 32 months, from November 1, 2016, to July 1, 2019. The events were grouped by whether staff pursued criminal charges after the incident. Descriptive statistics and regression models were used to describe the data and identify predictive variables.Data were reviewed from 9,654 admissions, of which 124 patient encounters involved assaults on staff. Overall, 27 (22%) of 124 assaults on staff resulted in staff pursuing criminal charges. Regression models indicated that criminal history (odds ratio [OR]=2.18, 95% CI=1.26-3.78, p=0.006), age (OR=0.92, 95% CI=0.91-0.94, p0.001), and diagnosis of chronic mental illness with psychotic symptoms (OR=7.23, 95% CI=1.49-35.04, p=0.01) predicted patient assaults resulting in contact with law enforcement. Several variables were not statistically significantly associated with filing of criminal charges, including race, gender, degree of injury from the assault, number of instances of restraint, and number of as-needed medications.This is the largest quantitative study to examine the demographic and clinical factors that may play a role in whether staff pursue criminal charges against patients on inpatient psychiatric units. The results suggest that certain patients are more likely to be reported to law enforcement. Institutions should monitor factors that increase the likelihood of assaults on staff resulting in criminal charges and create policies that mitigate discrepancies in criminal justice involvement.

Background Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects. Methods We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by previously established validity measures. Results Nine studies were identified, with a total of 225 participants, of whom 63% were male, and 37% were female. Six studies included methadone-maintained persons with OUD; four studies included buprenorphine-maintained persons with OUD; and three studies included healthy persons as comparison groups. Either additional doses of OAT or other opioids – morphine, oxycodone, hydromorphone, or remifentanil – were administered. In seven studies, persons with OUD on OAT did not experience analgesia, despite receiving opioid doses up to 20 times greater than those clinically used to treat severe pain among the opioid naive. Conversely, in two studies, high-potency opioids did produce analgesia, albeit with greater abuse potential. Notably, persons with OUD on OAT remained vulnerable to respiratory depression. Conclusions Although persons with OUD on OAT can derive analgesic effects from opioids, high-potency compounds may be required to achieve clinically significant pain relief. Further, persons with OUD on OAT may remain vulnerable to opioid-induced abuse potential and respiratory depression. Together, these finding have clinical, methodological, and mechanistic implications for the treatment of acute pain in the context of OAT.

Background: Critically ill patients with COVID-19 infection on extracorporeal membrane oxygenation (ECMO) face high morbidity and mortality. Palliative care consultation may benefit these patients and their families. Prior to the pandemic, our institution implemented a policy of automatic palliative care consultation for all patients on ECMO due to the high mortality, medical complexity, and psychosocial distress associated with these cases. Objectives: The main objective was to describe the role of the palliative care team for patients on ECMO for COVID-19 infection. The secondary objective was to describe the clinical outcomes for this cohort. Design: Case series. Settings/Subjects: All patients age 18 or older infected by the novel coronavirus who required cannulation on ECMO from March through July of 2020, at an urban, academic medical center in the United States. Inter-disciplinary palliative care consultation occurred for all patients. Results: Twenty-three patients (median age 43 years [range 28-64], mean body mass index 34.9 kg/m2 [SD 9.2], 65% Hispanic ethnicity) were cannulated on ECMO. Eleven patients died during the hospitalization (48%). Patients older than 50 years of age demonstrated a trend toward increased odds of death compared to those younger than 50 years of age (OR 9.1, P = 0.07). Patients received an average of 6.8 (SD 3.7) palliative clinical encounters across all disciplines. The actions provided by the palliative care team included psychosocial support and counseling, determination of surrogate decision maker (for 100% of patients), pain management (83%), and non-pain symptom management (83%). Conclusions: Here, we present one of the first studies describing the patient characteristics, outcomes, and palliative care actions for critically ill patients with COVID-19 on ECMO. Almost half of the patients in this cohort died during their hospitalization. Given the high morbidity and mortality of this condition, we recommend involvement of palliative care for patients/families with COVID-19 infection who are on ECMO. The impact of palliative care on patient and family outcomes, such as symptom control, satisfaction with communication, rates of anxiety, and grief experience merits further investigation.

The mechanisms by which childhood maltreatment increases anxiety is unclear, but a propensity for increased defensive behavior in rodent models of early life stress (ELS) suggests that work in rodents may clarify important mechanistic details about this association. A key challenge in studying the effects of ELS on defensive behavior in rodents is the plethora of inconsistent results. This is particularly prominent with the maternal separation (MS) literature, one of the most commonly used ELS models in rodents. To address this issue we conducted a systematic review and meta-analysis, examining the effects of MS on exploratory-defensive behavior in mice and rats using the open field test (OFT) and the elevated plus maze (EPM). This search yielded a total of 49 studies, 24 assessing the effect of MS on behavior in the EPM, 11 tested behavior in the OFT, and 14 studies provided data on both tasks. MS was associated with increased defensive behavior in rats (EPM: Hedge’s g = −0.48, p = 0.02; OFT: Hedge’s g = −0.33, p = 0.05), effect sizes that are consistent with the anxiogenic effect of early adversity reported in humans. In contrast, MS did not alter exploratory behavior in mice (EPM: Hedge’s g = −0.04, p = 0.75; OFT: Hedge’s g = −0.03, p = 0.8). There was a considerable amount of heterogeneity between studies likely related to the lack of standardization of the MS protocol. Together, these findings suggest important differences in the ability of MS to alter circuits that regulate defensive behaviors in mice and rats.

OBJECTIVE: Racial and ethnic disparities are well documented in psychiatry, yet suboptimal understanding of underlying mechanisms of these disparities undermines diversity, inclusion, and education efforts. Prior research suggests that implicit associations can affect human behavior, which may ultimately influence healthcare disparities. This study investigated whether racial implicit associations exist among medical students and psychiatric physicians and whether race/ethnicity, training level, age, and gender predicted racial implicit associations. METHODS: Participants completed online demographic questions and 3 race Implicit Association Tests (IATs) related to psychiatric diagnosis (psychosis vs. mood disorders), patient compliance (compliance vs. non-compliance), and psychiatric medications (antipsychotics vs. antidepressants). Linear and logistic regression models were used to identify demographic predictors of racial implicit associations. RESULTS: The authors analyzed data from 294 medical students and psychiatric physicians. Participants were more likely to pair faces of Black individuals with words related to psychotic disorders (as opposed to mood disorders), non-compliance (as opposed to compliance), and antipsychotic medications (as opposed to antidepressant medications). Among participants, self-reported White race and higher level of training were the strongest predictors of associating faces of Black individuals with psychotic disorders, even after adjusting for participant age. CONCLUSIONS: Racial implicit associations were measurable among medical students and psychiatric physicians. Future research should examine (1) the relationship between implicit associations and clinician behavior and (2) the ability of interventions to reduce racial implicit associations in mental healthcare.

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Studies have demonstrated the disproportionate impact of COVID-19 on patients from racial and ethnic minorities. Black and Hispanic people suffer disproportionately high rates of infection with SARS-CoV-2, hospitalization, and mortality, compared to non-Hispanic White people. However, case fatality rates have been shown to be similar across racial and ethnic groups. Less is known about the factors underpinning the similar case fatality rates between different racial and ethnic populations. METHODS: This retrospective cohort study analyzed outcomes for patients with COVID-19 hospitalized at MedStar Health institutions between March 1st, 2020 and July 1st, 2020. MedStar Health is a large health system with 9 hospitals in the Baltimore-Washington DC region. Data was abstracted from electronic health records, with patients stratified based on their race and ethnicity. The primary outcome was survival to hospital discharge, and secondary outcomes included need for mechanical ventilation. Statistical analyses included descriptive statistics and multi-variate logistic regressions. RESULTS: 3,165 patients were included in this analysis. The mean age of the cohort was 60.2 years (SD 17.3) and 49% were female. 14.7% were non-Hispanic White patients, 57.2% were non-Hispanic Black patients, and 20.7% were Hispanic. Hispanic patients were significantly younger than the cohort, with a mean age of 50.0 years. The overall survival of this cohort was 84.3%, with 79.8% survival for non-Hispanic White patients, 83.3% for non-Hispanic Black patients, and 89.8% for Hispanic patients. Hispanic patients had lower odds of death than non-Hispanic White patients (OR=0.45, CI 0.32-0.63), but this difference was no longer present when controlling for patient age. Non-Hispanic Black patients (OR=1.35, CI 1.04-1.75) and Hispanic patients (OR=1.43, CI 1.06-1.93) had significantly increased odds of needing mechanical ventilation, with persistence of this difference when controlling for age, gender, insurance, and comorbidities. CONCLUSIONS: In this large cohort of patients from the Baltimore-Washington DC region hospitalized for SARS-CoV-2 infection, we demonstrate that patients of Hispanic ethnicity have higher odds of severe illness, as defined by need for mechanical ventilation, but lower hospital mortality than non-Hispanic White patients. The lower hospital mortality rate is likely mediated by the younger age of this group. CLINICAL IMPLICATIONS: Policy makers should consider interventions to target the social determinants such as differences in access to health care and risk of exposure to COVID-19 that may account for the higher odds of severe infection and delayed presentation among Hispanic patients. Additionally, our findings suggest that Hispanic community may be shouldering a disproportionate burden of chronic illness related to surviving severe COVID-19. DISCLOSURES: No relevant relationships by Muhtadi Alnababteh, source=Web Response No relevant relationships by Victor Avila-Quintero, source=Web Response No relevant relationships by Jose Flores, source=Web Response No relevant relationships by Hunter Groninger, source=Web Response No relevant relationships by Nina Laing, source=Web Response No relevant relationships by Anirudh RAO, source=Web Response No relevant relationships by Akram Zaaqoq, source=Web Response

IMPORTANCE: Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. OBJECTIVE: To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes. DATA SOURCES: PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019. EVIDENCE REVIEW: Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS: Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I(2) > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication. CONCLUSIONS AND RELEVANCE: This study’s findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.