Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

The Importance of Both Individual Differences and Dyadic Processes in Children's Emotion Expression.

Although children display strong individual differences in emotion expression, they also engage in emotional synchrony or reciprocity with interaction partners. To understand this paradox between trait-like and dyadic influences, the goal of the current study was to investigate children's emotion expression using a Social Relations Model (SRM) approach. Playgroups consisting typically of four same-sex unfamiliar nine-year-old children (N = 202) interacted in a round-robin format (6 dyads per group). Each dyad completed two 5-minute tasks, a challenging frustration task and a cooperative planning task. Observers coded children's emotions during the tasks (happy, sad, angry, anxious, neutral) on a second-by-second basis. SRM analyses provided substantial evidence of both the trait-like nature of children's emotion expression (through significant effects for actor variance, multivariate actor-actor correlations, and multivariate intrapersonal correlations) and the dyadic nature of their emotion expression (through significant effects for partner variance, relationship variance, dyadic reciprocity correlations, and multivariate interpersonal correlations).

Concurrent transmission of multiple carbapenemases in a long-term acute-care hospital.

OBJECTIVE: We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying blaVIM (VIM-CRPA) and Enterobacterales carrying blaKPC (KPC-CRE) at a long-term acute-care hospital (LTACH A). METHODS: We defined an incident case as the first detection of blaKPC or blaVIM from a patient's clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had blaKPC, 11 had blaVIM, and 7 had blaVIM and blaKPC. Also, blaKPC were identified from 7 Enterobacterales, and all blaVIM were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates. CONCLUSIONS: Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission.

Distinct Origins and Transmission Pathways of blaKPC Enterobacterales across Three U.S. States.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of blaKPC-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of blaKPC-carrying Klebsiella pneumoniae ST258, and clonal expansion of blaKPC-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of blaKPC-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of blaKPC plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.

Containment of a Verona Integron-Encoded Metallo-Beta-Lactamase-Producing Pseudomonas aeruginosa Outbreak Associated With an Acute Care Hospital Sink-Tennessee, 2018-2020.

Background: Contaminated healthcare facility wastewater plumbing is recognized as a source of carbapenemase-producing organism transmission. In August 2019, the Tennessee Department of Health (TDH) identified a patient colonized with Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-CRPA). A record review revealed that 33% (4 of 12) of all reported patients in Tennessee with VIM had history of prior admission to acute care hospital (ACH) A intensive care unit (ICU) Room X, prompting further investigation. Methods: A case was defined as polymerase chain reaction detection of blaVIM in a patient with prior admission to ACH A from November 2017 to November 2020. The TDH performed point prevalence surveys, discharge screening, onsite observations, and environmental testing at ACH A. The VIM-CRPA isolates underwent whole-genome sequencing (WGS). Results: In a screening of 44% (n = 11) of 25 patients admitted to Room X between January and June 2020, we identified 36% (n = 4) colonized with VIM-CRPA, resulting in 8 cases associated with Room X from March 2018 to June 2020. No additional cases were identified in 2 point-prevalence surveys of the ACH A ICU. Samples from the bathroom and handwashing sink drains in Room X grew VIM-CRPA; all available case and environmental isolates were found to be ST253 harboring blaVIM-1 and to be closely related by WGS. Transmission ended after implementation of intensive water management and infection control interventions. Conclusions: A single ICU room's contaminated drains were associated with 8 VIM-CRPA cases over a 2-year period. This outbreak highlights the need to include wastewater plumbing in hospital water management plans to mitigate the risk of transmission of antibiotic-resistant organisms to patients.

Emotion transmission in peer dyads in middle childhood.

This study investigated emotion transmission among peers during middle childhood. Participants included 202 children (111 males; race: 58% African American, 20% European American, 16% Mixed race, 1% Asian American, and 5% Other; ethnicity: 23% Latino(a) and 77% Not Latino(a); Mincome  = $42,183, SDincome  = $43,889; Mage  = 9.49; English-speaking; from urban and suburban areas of a mid-Atlantic state in the United States). Groups of four same-sex children interacted in round-robin dyads in 5-min tasks during 2015-2017. Emotions (happy, sad, angry, anxious, and neutral) were coded and represented as percentages of 30-s intervals. Analyses assessed whether children's emotion expression in one interval predicted change in partners' emotion expression in the next interval. Findings suggested: (a) escalation of positive and negative emotion [children's positive (negative) emotion predicts an increase in partners' positive (negative) emotion], and (b) de-escalation of positive and negative emotion (children's neutral emotion predicts a decrease in partners' positive or negative emotion). Importantly, de-escalation involved children's display of neutral emotion and not oppositely valenced emotion.

Children's social information processing predicts both their own and peers' conversational remarks.

The goal of the current study was to investigate whether children's social information processing (SIP) predicts their conversations with peers, including both their remarks to peers and peers' remarks to them. When children (N = 156; 55% male; United States; Representation by Race: 60% African American, 18% Mixed race, 15% European American, 7% Other; Representation by Latino/a Ethnicity: 22% Latino/a, 78% Not Latino/a; Mincome = $39,419) were 8 years old, we assessed their aggressive and prosocial SIP using the Social Information Processing Application (SIP-AP). When children were 9 years old, they participated in playgroups typically consisting of four same-sex unfamiliar children who interacted in a round-robin format. Each dyad completed a five-minute frustration task and a five-minute planning task. Observers coded children's verbalizations into six prosocial categories (Suggest, Agree, Solicit Input, Ask, Encourage, State Personal) and four antisocial categories (Command, Disagree, Discourage, Aggress). Children with higher aggressive SIP made more antisocial and fewer prosocial statements, whereas children with higher prosocial SIP made more prosocial and fewer antisocial statements. Furthermore, children with higher aggressive SIP elicited more antisocial and fewer prosocial statements from peers, whereas children with higher prosocial SIP elicited more prosocial and fewer antisocial statements from peers. Children's antisocial and prosocial remarks mediated relations between their aggressive SIP and peers' subsequent antisocial and prosocial remarks. Findings are discussed in terms of: (a) the use of SIP to predict more subtle social behaviors in children's social interaction, and (b) cycles of social interactions that maintain and reinforce children's SIP patterns. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A comprehensive review of cerebral oximetry in cardiac surgery.

BACKGROUND: Patients who undergo cardiac surgery are at increased risk of stroke, postoperative cognitive decline, and delirium. These neurocognitive complications have led to increased costs, intensive care unit stays, morbidity, and mortality. As a result, there is a significant push to mitigate any neurological complications in cardiac surgery patients. Near-infrared spectroscopy to measure regional cerebral oxygen saturations has gained consideration due to its noninvasive and user-friendly nature. Cerebral oximetry desaturations during cardiac surgery have been linked to an array of adverse clinical outcomes. However, the most effective intraoperative interventions to protect this vulnerable patient population have yet to be ascertained. AIM OF STUDY: To provide a comprehensive summary of the intraoperative management for cerebral oximetry desaturations during cardiac surgery. The review highlights clinical outcomes from cerebral oximetry use to quantify the importance of identifying cerebral desaturations during cardiac surgery. The review then interrogates possible interventions for cerebral oximetry desaturations in an effort to determine which interventions are most efficacious and to enlighten possible areas for further research. METHODS: A narrative review of randomized controlled trials, observational studies, and systematic reviews with metanalyses was performed through August 2021. RESULTS: There is significant heterogeneity among patient populations for which cerebral oximetry monitoring has been studied in cardiac surgery. Further, the definition of a clinically significant cerebral desaturation and the assessment of neurocognitive outcomes varied substantially across studies. As a result, metanalysis is challenging and few conclusions can be drawn. Cerebral oximetry use during cardiac surgery has not been associated with improvements in neurocognitive outcomes, morbidity, or mortality to date. The evidence to support a particular intervention for an acute desaturation is equivocal. CONCLUSIONS: Future research is needed to quantify a clinically significant cerebral desaturation and to determine which interventions for an acute desaturation effectively improve clinical outcomes.

Susceptibility to peer influence in adolescents: Associations between psychophysiology and behavior.

The current study investigated in-the-moment links between adolescents' autonomic nervous system activity and susceptibility to three types of peer influence (indirect, direct, continuing) on two types of behavior (antisocial, prosocial). The sample included 144 racially ethnically diverse adolescents (46% male, 53% female, 1% other; M age  = 16.02 years). We assessed susceptibility to peer influence behaviorally using the Public Goods Game (PGG) while measuring adolescents' mean heart rate (MHR) and pre-ejection period (PEP). Three key findings emerged from bivariate dual latent change score modeling: (1) adolescents whose MHR increased more as they transitioned from playing the PGG alone (pre-influence) to playing while simply observed by peers (indirect influence) displayed more prosocial behavior; (2) adolescents whose PEP activity increased more (greater PEP activity = shorter PEP latency) as they transitioned from indirect influence to being encouraged by peers to engage in antisocial behavior (direct influence) engaged in more antisocial behavior; and (3) adolescents whose PEP activity decreased less as they transitioned from direct influence on prosocial behavior to playing the PGG alone again (continuing influence) displayed more continuing prosocial behavior (marginal effect). The discussion focuses on the role of psychophysiology in understanding adolescents' susceptibility to peer influence.

The prevalence of undiagnosed postoperative lower limb lymphedema among gynecological oncology patients.

OBJECTIVE: Lower limb lymphedema (LLL) is a common postoperative complication among gynecological oncology patients following lymph node resection. In the absence of a screening strategy, LLL is frequently diagnosed only through patient's self-reported symptoms. This study investigated the prevalence of undiagnosed postoperative LLL among gynecological oncology patients and identified the associated risk factors. MATERIALS AND METHODS: This was a cross-sectional postal questionnaire survey at a tertiary gynecological oncology center. Women with gynecological malignancies who underwent lymph node (inguinal/pelvic/para-aortic) resection between 2010 and 2017 were eligible. The Gynecological Cancer Lymphedema Questionnaire (GCLQ) was used and those with a score of ≥4 were referred to a lymphedema specialist for clinical confirmation. RESULTS: Among 376 eligible women, postoperative LLL was already diagnosed in 45/376 (12%) women. In the remaining women, 117/331 (35.3%) completed the GCLQ, of which 67/117 (57.3%) scored ≥4. Fifty-five women (55/67, 82.1%) were assessed by a lymphedema specialist and eight cases of postoperative LLL were confirmed. In the 12/67 who declined a clinical assessment, they reported no evidence of LLL. The prevalence of undiagnosed postoperative LLL in our study was 8/117 (6.8%, 95% C.I. 2.3-11.4). On univariate analysis, older women were more likely to have undiagnosed postoperative LLL. CONCLUSIONS: Undiagnosed postoperative LLL is not uncommon among gynecological oncology patients, especially in older patients. No vulvar cancer patient had undiagnosed LLL. Increased awareness and improved strategies for lymphedema screening are required after lymph node surgery in gynecological oncology.

Evaluating parental knowledge of pediatric burns first aid in Ireland and the effectiveness of an educational intervention improving knowledge.

AIM: Burns represent a large portion of injuries attending emergency departments each year, with children accounting for the biggest proportion. Appropriate first aid has been shown to help improve the outcome of burns, and decrease the need for surgical intervention. Several studies outside of Ireland demonstrate inadequate parental knowledge of burns first aid, but few evaluated interventions to improve knowledge. Consequently our aim was to assess parental/caregiver knowledge in Ireland, and determine if knowledge levels could be raised following a short educational video intervention. METHODS: An educational video based on current European and British best practice guidelines was produced and shown to parents/caregivers waiting in the Pediatric Outpatients Department after a previously validated pre-intervention questionnaire was completed. A post intervention questionnaire was completed following the video. Questionnaires assessed demographics, previous experience and included scenarios to test parental knowledge. RESULTS: 112 parents/caregivers (81.3% female (n = 91), 18.8% male (n = 21)) were questioned. Baseline knowledge was found to be poor overall, however this significantly improved with a simple educational video (pre-score 31.9%, post-test mean score knowledge 92.1%). Pre- and post-test scores showed a statistical significance (x2 = 71.117, P < 0.001, 95% CI).No other variables analysed were shown to be statistically significant predictors of pre- or post-test scores (all p > 0.05). CONCLUSION: The study found poor parental knowledge of burns first aid in Ireland and shows the use of an educational video was effective in raising knowledge levels.

Pre-Pandemic Peer Relations Predict Adolescents' Internalizing Response to Covid-19.

The goal of the current longitudinal study was to investigate the role of adolescents' peer victimization and aggression prior to COVID-19 on the change in their depressive and anxious symptoms from pre- to mid-pandemic. We hypothesized that, although adolescents overall would display an increase in internalizing symptoms from pre- to mid-pandemic, this response would be weakened or perhaps even reversed when adolescents experienced high levels of victimization or aggression prior to the pandemic. Participants included 96 racially/ethnically diverse adolescents (42 males, 53 females; 1 other) with an average age of 16.79 years (SD = 0.60). At Time 1 (T1; June 2019 through February 2020; pre-pandemic), adolescents completed self-report measures of their peer relations (aggression, victimization) and internalizing symptoms (depressive, anxious). At Time 2 (T2; May through July 2020; mid-pandemic), adolescents completed self-report measures of their internalizing symptoms (depressive, anxious). On average, adolescents' anxious and depressive symptoms increased from T1 to T2, although they exhibited substantial variability, with reports ranging from decreasing symptoms to increasing symptoms. Although on average adolescents reported increases in anxious symptoms from T1 to T2, adolescents with higher T1 peer victimization reported less positive change in anxious symptoms. Similarly, although on average adolescents reported increases in depressive symptoms from T1 to T2, adolescents with higher levels of T1 aggression reported less positive change in depressive symptoms from T1 to T2. Discussion focused on restrictions on in-person peer interactions necessitated by COVID-19 that may reduce adolescents' distress when their pre-pandemic daily lives were characterized by negative peer relations.

Phylogenetic Analysis Reveals Source Attribution Patterns for Campylobacter spp. in Tennessee and Pennsylvania.

Campylobacteriosis is the most common bacterial foodborne illness in the United States and is frequently associated with foods of animal origin. The goals of this study were to compare clinical and non-clinical Campylobacter populations from Tennessee (TN) and Pennsylvania (PA), use phylogenetic relatedness to assess source attribution patterns, and identify potential outbreak clusters. Campylobacter isolates studied (n = 3080) included TN clinical isolates collected and sequenced for routine surveillance, PA clinical isolates collected from patients at the University of Pennsylvania Health System facilities, and non-clinical isolates from both states for which sequencing reads were available on NCBI. Phylogenetic analyses were conducted to categorize isolates into species groups and determine the population structure of each species. Most isolates were C. jejuni (n = 2132, 69.2%) and C. coli (n = 921, 29.9%), while the remaining were C. lari (0.4%), C. upsaliensis (0.3%), and C. fetus (0.1%). The C. jejuni group consisted of three clades; most non-clinical isolates were of poultry (62.7%) or cattle (35.8%) origin, and 59.7 and 16.5% of clinical isolates were in subclades associated with poultry or cattle, respectively. The C. coli isolates grouped into two clades; most non-clinical isolates were from poultry (61.2%) or swine (29.0%) sources, and 74.5, 9.2, and 6.1% of clinical isolates were in subclades associated with poultry, cattle, or swine, respectively. Based on genomic similarity, we identified 42 C. jejuni and one C. coli potential outbreak clusters. The C. jejuni clusters contained 188 clinical isolates, 19.6% of the total C. jejuni clinical isolates, suggesting that a larger proportion of campylobacteriosis may be associated with outbreaks than previously determined.

Validation of the Social Information Processing Application (SIP-AP) across genders, socioeconomic levels, and forms of aggression.

The goals of the current study were to (a) replicate the factor structure of the Social Information Processing Application (SIP-AP), (b) evaluate the measurement invariance of the SIP-AP across genders, socioeconomic (SES) levels, and forms of aggression, and (c) assess the convergent validity of the SIP-AP through associations with aggression, social competence, and rule-breaking behavior. Participants were 189 racially/ethnically diverse children (53% male; Mage = 8.50 years) who completed the SIP-AP. Parents reported on children's aggression and social competence, children reported on their aggression, and we observed children's rule-breaking behavior. A five-factor model including Hostile Cue Interpretations, Aggressive Goals, Aggressive Responses, Aggressive Response Evaluations, and Prosocial SIP replicated in this sample. The model was invariant across genders, SES levels, and forms of aggression (physical, relational, covert, property destruction). Girls reported more Aggressive Goals than boys. Children from more economically disadvantaged families reported higher levels of Hostile Cue Interpretations, Aggressive Goals, and Aggressive Response Evaluations. Aggression was related to all SIP constructs in expected directions, social competence was negatively associated with Hostile Cue Interpretations, and rule-breaking behavior was positively linked to Aggressive Goals, Aggressive Responses, and Aggressive Response Evaluations. Results are discussed in terms of the psychometric strengths of the SIP-AP. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Levels and Instability of Daily Self-Esteem in Adolescents: Relations to Depressive and Anxious Symptoms.

The current study examined whether individual differences in depressive and anxious symptoms relate to level of daily self-esteem and instability of daily self-esteem in adolescence. Participants were a racially and ethnically diverse sample of adolescents (79 girls, 65 boys; M age = 13.53 years). Adolescents reported on their depressive and anxious symptoms during a baseline home visit. Then, adolescents reported on their daily self-esteem over the course of 12 consecutive days. Using hierarchical linear modeling analyses, level of daily self-esteem was negatively associated with depressive but not anxious symptoms. In addition, a positive relation emerged between instability of daily self-esteem and depressive symptoms when controlling for level of self-esteem; a similar relation did not emerge for anxious symptoms. The differential findings that emerged between both level and instability of daily self-esteem and depressive versus anxious symptoms may be linked to differences in the temporal orientation of these two types of internalizing symptoms; specifically, depressive symptoms result from backward-looking rumination over previous experiences, whereas anxious symptoms emerge from forward-looking worry about future events (Wenze et al., 2012).

The role of potassium and host calcium signaling in Toxoplasma gondii egress.

Toxoplasma gondii is an obligate intracellular parasite and replicates inside a parasitophorous vacuole (PV) within the host cell. The membrane of the PV (PVM) contains pores that permits for equilibration of ions and small molecules between the host cytosol and the PV lumen. Ca2+ signaling is universal and both T. gondii and its mammalian host cell utilize Ca2+ signals to stimulate diverse cellular functions. Egress of T. gondii from host cells is an essential step for the infection cycle of T. gondii, and a cytosolic Ca2+ increase initiates a Ca2+ signaling cascade that culminates in the stimulation of motility and egress. In this work we demonstrate that intracellular T. gondii tachyzoites are able to take up Ca2+ from the host cytoplasm during host cell signaling events. Both intracellular and extracellular Ca2+ sources are important in reaching a threshold of parasite cytosolic Ca2+ needed for successful egress. Two peaks of Ca2+ were observed in egressing single parasites with the second peak resulting from Ca2+ entry. We patched infected host cells to allow the delivery of precise concentrations of Ca2+ for the stimulation of motility and egress. Using this approach of patching infected host cells, allowed us to determine that increasing the host cytosolic Ca2+ to a specific concentration can trigger egress, which is further accelerated by diminishing the concentration of potassium (K+).

A New Promising Anti-Infective Agent Inhibits Biofilm Growth by Targeting Simultaneously a Conserved RNA Function That Controls Multiple Genes.

Combating single and multi-drug-resistant infections in the form of biofilms is an immediate challenge. The challenge is to discover innovative targets and develop novel chemistries that combat biofilms and drug-resistant organisms, and thwart emergence of future resistant strains. An ideal novel target would control multiple genes, and can be inhibited by a single compound. We previously demonstrated success against Staphylococcus aureus biofilms by targeting the tRNA-dependent regulated T-box genes, not present in the human host. Present in Gram-positive bacteria, T-box genes attenuate transcription with a riboswitch-like element that regulates the expression of aminoacyl-tRNA synthetases and amino acid metabolism genes required for cell viability. PKZ18, the parent of a family of compounds selected in silico from 305,000 molecules, inhibits the function of the conserved T-box regulatory element and thus blocks growth of antibiotic-resistant S. aureus in biofilms. The PKZ18 analog PKZ18-22 was 10-fold more potent than vancomycin in inhibiting growth of S. aureus in biofilms. In addition, PKZ18-22 has a synergistic effect with existing antibiotics, e.g., gentamicin and rifampin. PKZ18-22 inhibits the T-box regulatory mechanism, halts the transcription of vital genes, and results in cell death. These effects are independent of the growth state, planktonic or biofilm, of the bacteria, and could inhibit emergent strains.

An integrated program of computer-presented and physical cognitive training exercises for children with attention-deficit/hyperactivity disorder.

BACKGROUND: This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data. METHODS: Children (n = 93, mean age 7.3 +/- 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU. RESULTS: Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009-0.01) while non-responders improved on none (p = 0.27-0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003). CONCLUSIONS: Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.