Empagliflozin for treating neutropenia and neutrophil dysfunction in 21 infants with glycogen storage disease 1b.

Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however, data in infants are missing. We report on efficacy and safety of empagliflozin in infants with GSD 1b. This is an international retrospective case series on 21 GSD 1b infants treated with empagliflozin (total treatment time 20.6 years). Before starting empagliflozin (at a median age of 8.1 months with a median dose of 0.3 mg/kg/day) 12 patients had clinical signs and symptoms of neutrophil dysfunction. Six of these previously symptomatic patients had no further neutropenia/neutrophil dysfunction-associated findings on empagliflozin. Eight patients had no signs and symptoms of neutropenia/neutrophil dysfunction before start and during empagliflozin treatment. One previously asymptomatic individual with a horseshoe kidney developed a central line infection with pyelonephritis and urosepsis during empagliflozin treatment. Of the 10 patients who were treated with G-CSF before starting empagliflozin, this was stopped in four and decreased in another four. Eleven individuals were never treated with G-CSF. While in 17 patients glucose homeostasis remained stable on empagliflozin, four showed glucose homeostasis instability in the introductory phase. In 17 patients, no other side effects were reported, while genital (n = 2) or oral (n = 1) candidiasis and skin infection (n = 1) were reported in the remaining four. Empagliflozin had a good effect on neutropenia/neutrophil dysfunction-related signs and symptoms and a favourable safety profile in infants with GSD 1b and therefore qualifies for further exploration as first line treatment.

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.

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.

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.

Structure of an open conformation of T7 DNA polymerase reveals novel structural features regulating primer-template stabilization at the polymerization active site.

The crystal structure of full-length T7 DNA polymerase in complex with its processivity factor thioredoxin and double-stranded DNA in the polymerization active site exhibits two novel structural motifs in family-A DNA polymerases: an extended ß-hairpin at the fingers subdomain, that interacts with the DNA template strand downstream the primer-terminus, and a helix-loop-helix motif (insertion1) located between residues 102 to 122 in the exonuclease domain. The extended ß-hairpin is involved in nucleotide incorporation on substrates with 5'-overhangs longer than 2 nt, suggesting a role in stabilizing the template strand into the polymerization domain. Our biochemical data reveal that insertion1 of the exonuclease domain makes stabilizing interactions that facilitate proofreading by shuttling the primer strand into the exonuclease active site. Overall, our studies evidence conservation of the 3'-5' exonuclease domain fold between family-A DNA polymerases and highlight the modular architecture of T7 DNA polymerase. Our data suggest that the intercalating ß-hairpin guides the template-strand into the polymerization active site after the T7 primase-helicase unwinds the DNA double helix ameliorating the formation of secondary structures and decreasing the appearance of indels.

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.

Pharmacological treatment of pain among persons with opioid addiction: A systematic review and meta-analysis with implications for drug development.

The clinical features and neurobiology of pain and opioid use disorder (OUD) are inextricably linked. Despite emerging evidence supporting the negative impact of ongoing pain in the treatment of OUD, the pharmacological management of pain in the presence of OUD has received limited attention. We sought to systematically review the studies investigating pharmacotherapies for pain among persons with OUD. Eligible studies had participants with OUD and outcomes including evoked or spontaneous pain. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Out of 1,097 studies that met the search criteria, 12 studies provided data relevant to the research question-five laboratory studies and seven clinical trials. Random effects pooled estimates suggested no significant difference between groups at baseline but a response favoring the active treatment group over placebo, with nonsignificant heterogeneity between studies. Findings from these studies provide preliminary evidence for analgesic and antihyperalgesic effects of gabapentin, GABA agonists, and NMDA antagonists among persons with OUD. To establish the tradeoffs between the analgesic effects and abuse liability of these compounds, further well-controlled clinical trials are required among persons with OUD. This review also underscores the need for methodological enhancement in drug development for pain in OUD. Future research should address the clinical and neurobiological overlap between pain- and addiction-related phenomena. Transdisciplinary approaches may identify biomarkers of these shared phenomena and their neural substrates. The development of novel therapeutics for pain in OUD may be accelerated by such integration of pain and addiction research.

Plant organellar DNA polymerases bypass thymine glycol using two conserved lysine residues.

Plant organelles cope with endogenous DNA damaging agents, byproducts of respiration and photosynthesis, and exogenous agents like ultraviolet light. Plant organellar DNA polymerases (DNAPs) are not phylogenetically related to yeast and metazoan DNAPs and they harbor three insertions not present in any other DNAPs. Plant organellar DNAPs from Arabidopsis thaliana (AtPolIA and AtPolIB) are translesion synthesis (TLS) DNAPs able to bypass abasic sites, a lesion that poses a strong block to replicative polymerases. Besides abasic sites, reactive oxidative species and ionizing radiation react with thymine resulting in thymine glycol (Tg), a DNA adduct that is also a strong block to replication. Here, we report that AtPolIA and AtPolIB bypass Tg by inserting an adenine opposite the lesion and efficiently extend from a Tg-A base pair. The TLS ability of AtPolIB is mapped to two conserved lysine residues: K593 and K866. Residue K593 is situated in insertion 1 and K866 is in insertion 3. With basis on the location of both insertions on a structural model of AtPolIIB, we hypothesize that the two positively charged residues interact to form a clamp around the primer-template. In contrast with nuclear and bacterial replication, where lesion bypass involves an interplay between TLS and replicative DNA polymerases, we postulate that plant organellar DNAPs evolved to exert replicative and TLS activities.

Who We Are Today: a National Survey of Diversity Among Psychiatry Program Directors.

OBJECTIVE: In March 2018, the American Association of Directors of Psychiatric Residency Training (AADPRT) formed the Diversity and Inclusion (D&I) Committee. One of the committee's goals was to understand the AADPRT membership's composition and their perceptions of D&I. This study's objective was to identify the demographic characteristics of the AADPRT membership. METHODS: Program directors were invited by email to participate in an anonymous survey. The survey collected participants' demographic information including gender, race/ethnicity, training background, age, disability/differently abled status, job role, geographic region where their program is located, type of program, and their program's community setting. RESULTS: Two hundred fifty six of 657 AADPRT members (39%) completed the survey. Respondents were mostly White (64.5%) followed by Asian/Southeast Asian (17.6%), Hispanic/Latinx (4.3%), and Black (1.6%). Only 13.3% of the participants were international medical graduates. Women were more prevalent (61.7%) than men (37.5%), and 9.4% self-identified as members of the LGBTQ+ Community. CONCLUSIONS: This study represents the first systematic investigation into the diversity among psychiatry program directors throughout the USA and Canada. Future qualitative studies are needed to better understand the reasons behind this initial study's findings. Potential concerns requiring exploration include the possibility of the program director role serving as a "glass ceiling" for some women and a "leaky pipeline" in academia for groups underrepresented in medicine.

Racial Implicit Associations in Psychiatric Diagnosis, Treatment, and Compliance Expectations.

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's 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.

A new allele of γ-kafirin gene coding for a protein with high lysine content in Mexican white sorghum germplasm.

BACKGROUND: Low protein digestibility and lysine content of white sorghum grain limit its use as a foodstuff. The increase in γ-kafirin cross-linking, has an important role in the reduction of protein digestibility. The objective of this study was to characterize the γ-kafirin gene in 12 Mexican tannin-free white sorghum genotypes and its relationship with protein digestibility and lysine content. RESULTS: Two alleles of γ-kafirin gene were identified: alleles 1 and 7. The predicted amino acid sequence of allele 7 showed seven point mutations; six were silent, and one missense (C235G), causing the substitution P79A in the deduced amino acid sequence. In silico analysis showed that γ-kafirin codified by allele 1 has five α-helixes without disulfide bonds, while γ-kafirin coding by allele 7 has four α-helixes and three disulfide bonds. Genotypes with allele 7 had higher lysine content than those with allele 1, showing no differences in the kafirin electrophoretic profile, neither a correlation with the protein content nor the in vitro pepsin digestibility. CONCLUSIONS: Mexican tannin-free white sorghum genotypes showed two γ-kafirin alleles, 1 and 7. Allele 7 was associated with higher lysine content; in silico analysis showed that the substitution of P79A in this allele could modify γ-kafirin secondary structure. © 2015 Society of Chemical Industry.

Labor patterns in women attempting vaginal birth after cesarean with normal neonatal outcomes.

OBJECTIVE: We sought to describe labor patterns in women with a trial of labor after cesarean (TOLAC) with normal neonatal outcomes. STUDY DESIGN: In a retrospective observational study at 12 US centers (2002 through 2008), we examined time interval for each centimeter of cervical dilation and compared labor progression stratified by spontaneous or induced labor in 2892 multiparous women with TOLAC (second delivery) and 56,301 nulliparous women at 37 0/7 to 41 6/7 weeks of gestation. Analyses were performed including women with intrapartum cesarean delivery, and also limiting only to women who delivered vaginally. RESULTS: Labor was induced in 23.4% of TOLAC and 44.1% of nulliparous women (P < .001). Cesarean delivery rates were 57.7% in TOLAC vs 19.0% in nulliparous women (P < .001). Oxytocin was used in 52.4% of TOLAC vs 64.3% of nulliparous women with spontaneous labor (P < .001) and 89.8% of TOLAC vs 91.6% of nulliparous women with induced labor (P = .099); however, TOLAC had lower maximum doses of oxytocin compared to nulliparous women: median (90th percentile): 6 (18) mU/min vs 12 (28) mU/min, respectively (P < .001). Median (95th percentile) labor duration for TOLAC vs nulliparous women with spontaneous labor from 4-10 cm was 0.9 (2.2) hours longer (P = .007). For women who entered labor spontaneously and achieved vaginal delivery, labor patterns for TOLAC were similar to nulliparous women. For induced labor, labor duration for TOLAC vs nulliparous women from 4-10 cm was 1.5 (4.6) hours longer (P < .001). For women who achieved vaginal delivery, labor patterns were slower for induced TOLAC compared to nulliparous women. CONCLUSION: Labor duration for TOLAC was slower compared to nulliparous labor, particularly for induced labor. By improved understanding of the rates of progress at different points in labor, this new information on labor curves in women undergoing TOLAC, particularly for induction, should help physicians when managing labor.

Congenital ADAMTS13 deficiency: a rare mimicker of immune thrombocytopenic purpura.

Congenital ADAMTS13 deficiency is a rare disease that leads to recurrent episodes of thrombotic thrombocytopenic purpura. We report a case that mimicked a recurring immune thrombocytopenic purpura in a child. Mild cases of ADAMTS13 deficiency may be initially confused with immune thrombocytopenic purpura if hemolytic anemia is not severe and renal or neurological symptoms are not present. Fresh frozen plasma is the treatment of choice in acute thrombotic thrombocytopenic purpura in ADAMTS13-deficient patients. The best long-term treatment for slightly symptomatic cases remains to be elucidated. Recombinant human ADAMTS13 factor will be a promising option when commercially available.

Nonclinical parameters affecting primary cesarean rates in the United States.

OBJECTIVE: Cesarean is the single most common operation in United States and has reached epidemic proportions in recent decades. Our objective was to study the effect of nonclinical parameters on primary cesarean rates in a large contemporary population. STUDY DESIGN: We designed a retrospective multicenter study using data obtained from electronic medical records from 19 U.S. hospitals between 2005 and 2007 (Consortium on Safe Labor Database), which included 145,764 term, singleton, nonanomalous, vertex, live births that included labor. The impact of nonclinical parameters (patient and provider characteristics, time of delivery, institutional policies, and insurance type) was investigated using modified Poisson regression methodology and classification and regression tree analysis. RESULTS: There were 125,517 vaginal and 20,247 cesarean deliveries. Using the multivariable model, the nonclinical parameters with statistical significance for primary cesarean were delivery during evening hours, a male provider, public insurance, and nonwhite race (p < 0.001). CONCLUSIONS: Cesarean rates are associated with several nonclinical factors. Further investigation into these factors might help to develop strategies to reduce their influence and hence the rates of cesarean.

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.

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. Psychiatrists and trainees' demographic predictors of implicit associations were also investigated. 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" (ie, negatively valenced) words (44.3%) vs "good" (ie, positively valenced) words (6.4%), and between externalizing words (41.7%) vs 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: racial implicit associations in a more generalizable sample; the relationship between race IATs and provider behavior; and 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.

Maternal death in the emergency department from trauma.

PURPOSE: Trauma during pregnancy is among leading causes of non-pregnancy-related maternal death (MD). This study describes risk factors for MD from trauma during pregnancy in a large urban population. METHODS: We queried an urban Level One Trauma Center registry for the medical records of pregnant women suffering trauma from 1990 to 2007. Associations were examined between maternal demographics, injury mode details, injury characteristics, and risk of maternal death upon arrival to the emergency room. RESULTS: Overall, 351 patients were identified. Most traumas was caused by motor vehicle collision (71.8 %), accounting for 78.9 % of MD, followed by gun shot wound (10.3 %), stabbing (8.5 %), falls (4.3 %), and assaults (4 %). Abdominal and head injuries were more frequent in cases of MD compared with patients admitted to the hospital (33.3 vs. 25.1 % abdominal, 55.6 vs. 29.4 % head; p < 0.001). A greater proportion of MDs were characterized by lack of restraint use (66.7 %) compared to women admitted to the hospital (47.7 %) and women discharged after observation (43.1 %); p = 0.014. ER deaths had more negative base excess scores than women who were admitted or discharged (-14 vs. -3 vs. -2; p < 0.001), lower blood pH values (6.96 vs. 7.40 vs. 7.44; p < 0.001), greater Injury Severity Scores (ISS) (44.4 vs. 11.49 vs. 2.66; p < 0.001), and lower Revised Trauma Scores (RTS) (0.5 vs. 7.49 vs. 7.83; p < 0.001). CONCLUSIONS: Lack of restraint use in the pregnant population is associated with increased MD. Although not validated in the pregnant population, the ISS and RTS were associated with maternal mortality outcomes.

Environmental risk management: A participatory diagnosis from a rural school in Colombia.

The rural population is potentially exposed to several environmental risks. Environmental risk management is a recurring challenge in rural educational communities that are far from large urban areas. Assessing and identifying the knowledge on prevention and response to environmental risks and natural disasters is fundamental for planning and designing educational programs for communities to face disasters. This article presented the practical application of a participatory methodology to obtain information about the knowledge and experience in the prevention and attention of environmental threats and natural disasters in the rural school Las Huacas, village of Quintana, municipality of Popayán, in the region of Cauca, Colombia. The diagnosis methodology consisted of three phases: preparatory, fieldwork and analytical. The participatory diagnosis allowed the construction of instruments and tools for social interaction, the conduction of dynamic workshops and the systematisation of the collected information. The results evidenced the lack of knowledge on environmental disasters and how parents and children must face them. The absence of communication facilities implied a high degree of vulnerability, which was compensated with the awareness, commitment and participation in the processes led by the educational community. The next challenge is the participatory construction of a scholar environmental risk-management plan supported on appropriated information and communication technologies. Contribution: This article presents the practical application of a participatory methodology to obtain information about the rural context and the knowledge and experience in the prevention and attention of environmental threats and natural disasters in a rural school in Cauca, Colombia.