Racial Implicit Associations in Child Psychiatry.

OBJECTIVE: Racial disparities in diagnosis and treatment are prevalent in child psychiatry, including disparate diagnosis rates of internalizing and externalizing disorders in Black and White children. However, limited research has investigated mechanisms that contribute to these disparities. This study examined child racial implicit associations in psychiatric clinicians and medical students to address this gap. METHOD: Psychiatrists and trainees completed an online survey including 2 race Implicit Association Tests (IATs) pairing child faces to words with either positive or negative valence, and words related to internalizing or externalizing behavioral problems. We further investigated psychiatrists' and trainees' demographic predictors of implicit associations. RESULTS: Data were analyzed from 235 psychiatrists and trainees (112 child and adolescent psychiatrists and fellows) who met inclusion criteria. Psychiatrists and trainees demonstrated greater moderate-to-strong association between Black child faces and "bad" words (44.3%) vs "good" words (6.4%), and between externalizing words (41.7%) and internalizing words (7.2%). Psychiatrists' and trainees' demographic characteristics including being female (ß = -0.12; 95% CI = -0.23 to -0.01; p < .05), Black (ß = -0.36; 95% CI = -0.54 to -0.18; p < .001), or an attending physician (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01) were significant predictors of decreased association between Black child faces and negative valence words. Being female was a significant predictor of decreased association between Black child faces and externalizing words (ß = -0.26; 95% CI = -0.45 to -0.06; p = .01). CONCLUSION: Participating psychiatrists and trainees demonstrated bias toward associating Black rather than White child faces with negative words and externalizing behavioral problems. Future research should examine the following: (1) racial implicit associations in a more generalizable sample, (2) the relationship between race IATs and provider behavior, and (3) interventions to reduce racial inequities in psychiatry, including individual and systemic solutions. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science.

Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression.

Objective: Ketamine has proved effective as a rapid-acting antidepressant agent, but treatment is not effective for everyone (approximately a quarter to a half of patients). Some adult studies have begun to investigate predictors of ketamine's antidepressant response, but no studies have examined this in adolescents with depression. Methods: We conducted a secondary data analysis of adolescents who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine for adolescents with treatment-resistant depression. We examined the relationship between 19 exploratory demographic and clinical variables and depression symptom improvement (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) at 1 and 7 days postinfusion. Results: Subjects who had fewer medication trials of both antidepressant medications and augmentation treatments were more likely to experience depression symptom improvement with ketamine. Subjects with shorter duration of their current depressive episode were more likely to experience depression symptom improvement with ketamine. Subjects currently being treated with selective serotonin reuptake inhibitor medications, and not being treated with serotonin-norepinephrine reuptake inhibitor medications, also experienced greater symptom improvement with ketamine. When receiving the midazolam control, less severe depressive symptoms, as measured by the Children's Depression Rating Scale (CDRS) (but not MADRS), and a comorbid attention-deficit/hyperactivity disorder diagnosis were associated with increased response. Conclusions: Findings should be viewed as preliminary and exploratory given the small sample size and multiple secondary analyses. Identifying meaningful predictors of ketamine response is important to inform future therapeutic use of this compound, however, considerably more research is warranted before such clinical guidance is established. The trial was registered in clinicaltrials.gov with the identifier NCT02579928.

Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

Importance: Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear. Objective: To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses. Data Sources: Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions. Study Selection: Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD. Data Extraction and Synthesis: Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses. Main Outcome Measures: Change in ADHD symptoms and discontinuations due to adverse events. Results: A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence). Conclusions and Relevance: Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.

Pharmacological and Somatic Treatment Effects on Suicide in Adults: A Systematic Review and Meta-Analysis.

Background: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. Methods: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. Results: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. Conclusion: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.Reprinted from Depress Anxiety 2022; 39:100-112, with permission from John Wiley and Sons. Copyright © 2022.

The Relationship Between Acute Dissociative Effects Induced by Ketamine and Treatment Response in Adolescent Patients with Treatment-Resistant Depression.

Objective: Ketamine has proven effective as a rapid-acting antidepressant agent. Several adult studies have investigated the association between ketamine's acute dissociative effects and depression response, but no studies have examined the association in adolescents with treatment-resistant depression (TRD). Methods: We conducted a secondary data analysis of 16 adolescent participants who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine in adolescents with depression. We examined the association between the acute dissociative symptoms (measured at 60 minutes following start of infusion using the Clinician-Administered Dissociative States Scale [CADSS], and its three subscales: depersonalization, derealization, amnesia) and response and depression symptom improvement at 1'day (using the Montgomery-Åsberg Depression Rating Scale). Results: Within the ketamine group, there were no significant associations between dissociation symptoms or CADSS subscale scores and magnitude of depression symptom improvement or likelihood of ketamine response. When receiving midazolam, there was no significant association between overall dissociation symptoms and magnitude or likelihood of response of depressive symptoms. Higher levels of symptoms on the 'depersonalization' CADSS subscale when receiving midazolam were associated with less improvement in depression symptoms at 1 day following infusion. Conclusions: In contrast to some adult literature, the current data do not show a relationship between acute dissociative effects and antidepressant response to ketamine in pediatric patients with TRD. Interpretation may be limited by the small sample size, reducing the power to detect small or medium associations. Future research should utilize larger samples to more definitively measure the magnitude of association between acute dissociative symptoms and later antidepressant response to ketamine and to assess the relationship to trial design (e.g., crossover vs. parallel trial, comparison condition utilized and number of infusions) within both adult and pediatric populations. ClinicalTrials.gov identifier: NCT02579928.

Systematic review and meta-analysis: Season of birth and schizophrenia risk.

OBJECTIVE: Winter birth has been hypothesized to be associated with increased schizophrenia risk for nearly a century. Major hypotheses regarding the potential etiological risk factors for schizophrenia such as vitamin D deficiency and virus exposure in utero are predicated based on the observation that risk of schizophrenia is higher in children born in winter months. METHODS: We conducted a systematic review and meta-analysis to examine the association between season and month of birth and risk of schizophrenia. We further investigated this relationship stratified by hemisphere. RESULTS: Forty-three studies spanning 30 countries and territories and 440,039 individuals with schizophrenia were included in this meta-analysis. Winter births were associated with a small but statistically significant increased risk of schizophrenia (OR 1.05, 95 % CI 1.03-1.07, p < 0.0001) and summer births were associated with a small but statistically significant decreased risk of schizophrenia (OR 0.96, 95 % CI 0.94-0.98, p = 0.0001). Stratified subgroup analysis demonstrated no significant difference between hemispheres in the risk of schizophrenia for either winter or summer births. CONCLUSIONS: Analysis using birth month data demonstrated a clear seasonal trend towards increased risk of schizophrenia being associated with winter birth months and decreased risk of schizophrenia in summer-to-fall months in the Northern but not Southern Hemisphere. These data suggest a small-but-substantial increased risk of schizophrenia in winter birth month. Further research needs to examine potential etiologic causes for this association.

Association Between Patient Race and Ethnicity and Outcomes With COVID-19: A Retrospective Analysis From a Large Mid-Atlantic Health System.

BACKGROUND: Members of racial and ethnic minority groups have been disproportionately impacted by coronavirus-2019 (COVID-19). The objective of the study is to describe associations between race and ethnicity on clinical outcomes such as need for mechanical ventilation and mortality. METHODS: Retrospective cohort study of patients with severe COVID-19 infection admitted within a large, not-for-profit healthcare system in the mid-Atlantic region between March and July, 2020. Patient demographic data and clinical outcomes were abstracted from the electronic health record. Logistic regressions were performed to estimate associations between race and ethnicity and the clinical outcomes. RESULTS: The study population (N = 2931) was stratified into 1 of 3 subgroups: non-Hispanic White (n = 466), non-Hispanic Black (n = 1611), and Hispanic (n = 654). The average age of White, Black, and Hispanic patients was 69 ± 17.06, 64 ± 15.9, and 50 ± 15.53 years old, respectively (P < .001). Compared to White patients, Black and Hispanic patients were at increased odds of needing mechanical ventilation due to COVID-19 pneumonia (odds ratio [OR] Black = 1.35, 95% confidence interval [CI] = 1.04 to 1.75, P < .05; OR Hispanic = 1.43, 95% CI = 1.06 to 1.93, P < .05). When compared to White patients, Hispanic patients were at decreased odds of death (OR = 0.45, 95% CI = 0.32 to 0.63, P < .001). However, when adjusting for age, there were no statistically significant differences in the odds of death between these groups (adjusted OR [aOR] Black = 1.05, 95% CI = 0.80 to 1.38, P = .71; aOR Hispanic = 1.10, 95% CI = 0.76 to 1.60, P = .62). CONCLUSION: Our analysis demonstrated that Hispanic patients were more likely require mechanical ventilation but had lower mortality when compared to White patients, with lower average age likely mediating this association. These findings emphasize the importance of outreach efforts to communities of color to increase prevention measures and vaccination uptake to reduce infection with COVID-19.

Social media use and body image issues among adolescents in a vulnerable Louisiana community.

Widespread concern has been expressed regarding unrealistic body image and adolescent eating disorder promoting content on social media (SM) platforms. Numerous research studies have examined the impact of SM on body image as well as social vulnerability on negative mental health outcomes. Despite this, few previous studies have examined the impact of SM on body image specifically in vulnerable, underserved, or predominantly minority communities. This study examines the impact of SM on body image issues (BII) in adolescents in a public school system where greater than 50% of the students live in impoverished households. In late 2019, high school student leaders in Northwest Louisiana developed a survey alongside Step Forward, a collective impact initiative. Questions investigated adolescent SM use and mental health in Caddo Parish, namely BII. Teachers within Caddo Parish Public School System administered the survey. Out of the 11,248 total high school students in the school system, nearly 50% were sampled for a sample size of 5,070. Hypotheses included: (1) females were more likely to use SM than males, (2) increasing time spent on SM would correlate with females reporting BII, with males remaining largely unaffected, and (3) highly visual social media (HVSM) platforms would be associated with greater reports of BII than non-HVSM platforms. Results showed females were more likely to use SM (p < 0.001) and report BII (p < 0.001) compared to males, while both sexes reported BII with increasing time spent on SM (p < 0.001). A diversity of platforms were associated with increased BII among SM users compared to non-users (p < 0.001): Pinterest, Reddit, Snapchat, TikTok, Twitter, and YouTube. This conclusion is tempered by the omission of race as a variable in the study design, the use of self-report, and the use of an unvalidated instrument. These findings suggest that the harmful association between SM use and BII may transcend culture and socioeconomic status for a broadly deleterious effect on adolescent mental wellbeing.

Sexual Orientation and Racial Bias in Relation to Medical Specialty.

Physician explicit and implicit biases involving race and sexual orientation (SO) affect patient and provider experiences in healthcare settings. An anonymous survey was disseminated nationally to graduating medical students, residents, and practicing physicians to evaluate SO and racial biases across medical specialties. SO explicit and implicit bias were measured with the Attitudes toward Lesbians and Gay Men Scale, short form (ATLG-S) and Gay-Straight Implicit Association Test (IAT). Racial explicit and implicit bias were measured with the Quick Discrimination Index (QDI) and the Black-White IAT. Medical specialty was associated with racial explicit bias and specialty prestige with Black-White IAT score. Medical specialty and specialty prestige were not associated with SO bias. Female sex, sexual and gender minority (SGM) identity, and decreased religiosity were associated with reduced SO and racial bias. Provider race was associated with racial implicit and explicit bias.

Teen Advisory Council Survey's Factors Associated With Self-Harming Thoughts.

Background: The evaluation of teens with self-harming thoughts (SHT) is a high-stakes task for physicians in community and emergency department (ED) settings. The lived experience of adolescents with stress and SHT provides an important source of insight for mental health professionals who evaluate and treat teens A snapshot of the lived experience of teens in northwest Louisiana was captured by the Step Forward Teen Advisory Council (TAC) in 2019. The TAC surveyed peers with the goal of identifying common stressors experienced by local teens in order to inform policy and practices in the local school system. The identification of stressors is a critical step in addressing SHT as adolescents who experience life stressors are at increased risk for self-harming thoughts (SHT), a known precursor to self-harm and suicide. Assessing youth for life stressors is a critical element of suicide prevention. Methods: Local teens queried 5,070 peers attending Caddo Parish schools to better understand the stressors faced by high school students in Northwest Louisiana using a student developed survey. Results were presented to peers at a virtual summit where teens developed action items to reduce stress and presented findings to local leaders. Their efforts ultimately lead to increased supports for students in local schools. Results: Over half of the teens surveyed reported stressors that negatively impacted their physical or emotional well-being. Students endorsing self-harming thoughts reported an average of 7.82 stressors as compared to 3.47 in peers without SHT. Teens with stressors at both home and school were more likely to experience SHT than teens with stressors in a single location. Conclusion: The Gen Z students who developed the TAC Survey identified stress as a major concern for teens in Northwest Louisiana. The TAC Survey data aligns local experience with established data regarding the association between stress, depression and SHT. Second, the results highlight the importance of diving deep to identify all stressors when assessing the risk of self-harm. Finally, the lived experience of local teens with SHT provides critical information for professionals to better understand risk for SHT and suicide in our region and beyond.

Does the SDMQ-9 Predict Changes in HbA1c Levels? An Ecuadorian Cohort.

Background and Objectives: Diabetes mellitus affects 422 million people around the world, positioning it as a major health problem. According to the WHO(World Health Organization), 90% corresponds to type 2. The shared-decision making (SDM) is a method used to facilitate patient control, medication, maintenance, and assessment of health status according to their priorities and preferences. With the application of SDM in patients with diabetes, it is expected there will be an increase in treatment adherence and a reduction in HbA1c levels. The aim of this study is to determine the predictors of the change in HbA1c. Material and Methods: A sample of 76 participants attending as endocrinology outpatients was obtained. Data collected within the sample included: sex, age, educational level, body mass index, and the level of SDM using the SDMQ-9. In addition, HbA1c levels were measured twice: at baseline and three months after the first measurement. Results: The linear regression indicates that the level of SDM is a significant predictor of the change in HbA1c, specifically in men. However, the direction of the relationship was a somewhat opposite trend than we expected. Higher levels of SDM imply an increase in HbA1c rather than a reduction. Conclusions: Contrary to the literature, our results shows that elevated levels of perceived SDM may be associated with worse diabetic control. However, more investigation is needed as these results are not generalizable, due to the specific population used and the sample size. Furthermore, to better understand the effect of SDM on the change in HbA1c in patients with poorly controlled diabetes.

Characteristics of Assaultive Patients Whom Inpatient Psychiatric Staff Report to Law Enforcement.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p<0.001), 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. CONCLUSIONS: 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.

The effects of stimulant dose and dosing strategy on treatment outcomes in attention-deficit/hyperactivity disorder in children and adolescents: a meta-analysis.

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.

Surgical repair of nasal septal perforations: A systematic review and meta-analysis.

BACKGROUND: A wide variety of techniques for the surgical repair of nasal septal perforations (NSPs) have been described. Surgical management of NSPs can be broadly divided into open versus endonasal approaches, with additional variables involving unilateral or bilateral flaps, use of grafts, and placement of splints. The objective of this study was to compare surgical approaches and their outcomes. METHODS: PubMed, EMBASE, and CINAHL Plus databases were examined for patients undergoing NSP repair. English-language studies reporting surgical management of patients with the primary diagnosis of NSP were included. Outcome measures of interest included perforation size, surgical approach characteristics, and success rate defined as complete closure assessed by surgeon postoperatively. The quality of articles was assessed with the methodological index for nonrandomized studies (MINORS) criteria. A random-effects model was used to calculate pooled proportions for the different outcomes. RESULTS: The electronic database search yielded 1076 abstracts for review. A total of 64 articles met the inclusion criteria, with 1591 patients: 1127 (71%) underwent an endonasal approach and 464 (29%) an open approach. The median (range) MINORS score was 10 (5-12) out of 16 points. Overall, 91% of patients had total closure (95% confidence interval [CI], 0.89-0.93, p < 0.01), with moderate heterogeneity between studies (I2  = 42.03%). There was no difference in closure success between open and endonasal approaches. Use of bilateral versus unilateral flaps, interposition grafts, and intranasal splints and packing were not associated with differences in outcomes. CONCLUSION: Nasal septal perforation surgical repair success rates are comparable regardless of technique.

Pharmacological and somatic treatment effects on suicide in adults: A systematic review and meta-analysis.

BACKGROUND: Suicide is a public health crisis. We conducted a systematic review and meta-analysis of the effects of psychopharmacologic and somatic therapies on suicide risk. METHODS: A systematic search of MEDLINE for studies evaluating the effects of pharmacologic (excluding antidepressants) or somatic interventions on suicide risk was conducted. Studies were included if they used a comparison group, reported on suicide death, assessed a psychopharmacological or somatic intervention, and included adults. Study quality was assessed using the Newcastle-Ottawa scale. Fifty-seven studies were included from 2940 reviewed citations. RESULTS: In bipolar disorder, lithium was associated with a reduction in the odds of suicide compared to active controls (odds ratio [OR] = .58, p = .005; k = 12) and compared to placebo/no lithium (OR = .46, p = .009; k = 9). In mixed diagnostic samples, lithium was associated with a reduction in the odds of suicide compared to placebo/no lithium (OR = .27, p < .001; k = 12), but not compared to active controls (OR = .89, p = .468; k = 7). In psychotic disorders, clozapine was associated with a reduction in the odds of suicide (OR = .46, p = .007; k = 7). Associations between suicide death and electroconvulsive therapy (OR = .77, p = .053; k = 11), non-clozapine antipsychotics in bipolar disorder (OR = .73, p = .090; k = 6) and antipsychotics in psychotic disorders (OR = .39, p = .069; k = 6) were not significant. There was no consistent relationship between antiepileptic mood stabilizers and suicide. There were insufficient studies to meta-analyze associations of suicide risk with vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, or transcranial direct current stimulation. CONCLUSION: Lithium and clozapine have consistent data supporting protective effects against suicide in certain clinical contexts.

Opioid-induced analgesia among persons with opioid use disorder receiving methadone or buprenorphine: A systematic review of experimental pain studies.

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 naïve. 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.

Parental Age and the Risk for Alzheimer's Disease in Offspring: Systematic Review and Meta-Analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide, accounting for 50-75% of all cases. While older maternal and paternal age at childbirth are established risk factors for Down syndrome which is associated with later AD, it is still not entirely clear whether parental age is a risk factor for AD. Previous studies have suggested contradictory findings. OBJECTIVES: We conducted a systematic review and meta-analysis to examine whether parental (maternal and paternal) age at birth was associated with AD and whether individuals born to younger or older parents were at an increased risk for AD. METHODS: Two reviewers searched the electronic database of PubMed for relevant studies. Eligibility for the meta-analysis was based on the following criteria: (1) studies involving patients with AD and an adequate control group, (2) case control or cohort studies, (3) studies investigating parental age. All statistical analyses were completed in STATA/IC version 16. RESULTS: Eleven studies involving 4,371 participants were included in the systematic review and meta-analysis. Meta-analysis demonstrated no significant association between maternal (weighted mean difference [WMD] 0.49, 95% CI -0.52 to 1.49, p = 0.34) and paternal age and AD (WMD 1.00, 95% CI -0.55 to 2.56, p = 0.21). Similarly, individuals born to younger (<25 years) or older parents (>35 years) did not demonstrate a differential risk for AD. CONCLUSIONS: Overall, this meta-analysis did not demonstrate an association between parental age and the risk of AD in offspring. These findings should be interpreted with caution given the limited power of the overall meta-analysis and the methodological limitations of the underlying studies as in many cases no adjustment for potential confounders was included.

Meta-Analysis: Hemodynamic Responses to Sub-anesthetic Doses of Ketamine in Patients With Psychiatric Disorders.

Ketamine, a medication traditionally used as an anesthetic, has increasingly been recognized as an effective treatment for psychiatric disorders. At sub-anesthetic doses (defined here as ≤ 0.5 mg/kg), ketamine treatment has been studied in patients with treatment-resistant depression (TRD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD). Transient increases in hemodynamic activity have been reported during and after ketamine treatment, which may be desirable properties in some anesthesia settings, but are generally undesirable in psychiatric settings. While ketamine doses used in psychiatry are lower than those used in anesthesia, there are published instances of early termination of psychiatric ketamine infusions due to elevations in blood pressure and heart rate. No unifying study has been conducted to examine the impact of sub-anesthetic ketamine doses on hemodynamic parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)] in psychiatric populations and to evaluate these changes across adult age groups. Here, data from 15 articles comprising a total N = 2,252 ketamine or esketamine treatments in adult participants were used to conduct a meta-analysis of treatment-induced hemodynamic changes. Ketamine/esketamine produced modest but significant increases in the variables of interest with an average SBP increase of 12.61 mm Hg (95% CI 10.40-14.82 mm Hg, z = 11.18, p < 0.0001), average DBP increase of 8.49 mm Hg (95% CI 6.89-10.09 mmHg, z = 10.41, p < 0.0001), and average heart rate increase of 4.09 beats per minute (95% CI 0.55-7.63 BPM), z = 2.27, p = 0.0235). Stratified subgroup analysis indicated no significant differences between ketamine and esketamine effects on blood pressure. Further analysis indicated that there was no significant effect of age on ketamine-induced changes in SBP, DBP, and HR. Taken together these data show that sub-anesthetic ketamine and esketamine induce small but significant increases in hemodynamic parameters that are transient in nature in adult psychiatric populations. While these data are reassuring, it is important for each treatment case to fully explore potential cardiovascular risks prior to initiating treatment.

Palliative Care for Patients on Extracorporeal Membrane Oxygenation for COVID-19 Infection.

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.