Etiological Networks of Attention-Deficit/Hyperactivity Disorder during Childhood and Adolescence.

OBJECTIVE: The purpose of the current study was to use network analysis techniques to parse relations between attention-deficit/hyperactivity disorder (ADHD) symptom domains, domains of executive function, and temperament traits. METHODS: Participants were 420 children aged 6-17 years (55% boys). The majority of the participants were Caucasian (72.86%) and 50% of the sample met diagnostic criteria for ADHD. Both parents and teachers provided ratings of participants' ADHD symptom severity. Parents completed questionnaires pertaining to participants' temperament traits, and participants completed well-validated laboratory measures of executive function. RESULTS: Results suggested effortful control as demonstrating the strongest relations with ADHD, particularly the parent-reported inattentive symptom domain. Additionally, negative effects appeared to demonstrate weaker but still notable relations primarily with the parent-reported hyperactive/impulsive symptom domain. Measures of executive function did not appear to demonstrate relations with any measures of ADHD symptoms or temperament traits. The results were generally replicated in a distinct sample (n = 732, 7-13 years, 63% boys, 81% White), although differences emerged pertaining to the role of surgency (i.e., related to the hyperactive/impulsive symptom domain in the replication but not the primary sample). CONCLUSIONS: Overall, findings provided support for the primary role of effortful control, as well as secondary roles for negative affect and surgency, as key risk markers for the characterization of ADHD. Additional exploration of the overlap between temperament and executive function, as pertaining to ADHD, may help clarify heterogeneity in phenotypes and suggest priorities for targeted interventions outside of traditional symptoms.

Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108).

PURPOSE: Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS: Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS: Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION: Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

Networks of ADHD and SCT Symptoms in Emerging Adulthood.

OBJECTIVE: Emerging adulthood (18-25 years) is a transitional and understudied developmental period. Yet, little is known about how specific symptoms of ADHD, as well as those from the related SCT domain, may differentially relate to one another during this period, if there are differences based on biological sex, or how closely results will align with adulthood. METHODS: We used network analysis techniques to explore the structure of ADHD and SCT symptoms within emerging adulthood, with additional comparisons between sexes as well as between emerging adulthood and adulthood. Using an online platform, 8,506 adults reported on their symptoms of ADHD and SCT. RESULTS: Symptoms grouped together within their respective domains during emerging adulthood with no significant differences in overall network structure between sexes. Similarly, network structure appeared to be robust across emerging adulthood and adulthood. CONCLUSION: Such consistency supports a conceptualization of ADHD in emerging adulthood as similar to adulthood.

Longitudinal attention-deficit/hyperactivity disorder symptom networks in childhood and adolescence: Key symptoms, stability, and predictive validity.

The current study visualized attention-deficit/hyperactivity disorder (ADHD) symptom networks in a longitudinal sample of participants across childhood and adolescence with exploratory examination of age and gender effects. Eight hundred thirty-six children ages 7-13 years were followed annually for 8 years in total. Across parent and teacher report, results suggested "is easily distracted" and "difficulties sustaining attention" as central symptoms across three testing points (i.e., Year 1, Year 3, and Years 5-8 collapsed). "Difficulties following instructions" and "intrudes/interrupts" also emerged as parent-reported central symptoms. Assessment of network structure across the three testing points suggested global robustness of relations among ADHD symptoms from midchildhood into early adolescence. However, relations among symptoms that cause problems in school settings (i.e., being easily distracted) were stronger in teacher-reported than parent-reported networks. When aggregated into a sum score, central symptoms during Year 1 predicted total difficulties related to mental health problems 5 years later just as well as all 18 symptoms. Central symptoms of ADHD may be useful as screeners of future emotional and behavioral difficulties. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Subgroups of Childhood ADHD Based on Temperament Traits and Cognition: Concurrent and Predictive Validity.

Efforts to parse ADHD's heterogeneity in the DSM system has generally relied on subtypes, or presentations, based on different symptom combinations. Promising recent work has suggested that biologically-relevant and clinically predictive subgroups may be identified via an alternative feature set based on either a) temperament traits or b) executive function measures. Yet, the potential additive ability of these domains for specifying ADHD sub-phenotypes remains unknown. We thus sought to determine whether temperament traits and executive function, together, could facilitate a more nuanced and clinically meaningful subgrouping of children with ADHD. Participants included 828 children aged 7-11 years (62% with ADHD, 38% female). Latent profile and community detection analyses using both temperament and cognitive input features provided support for a primarily temperament-based three-subgroup solution (i.e., "Mild," "Irritable," and "Surgent"), although the distinction between Surgent and Mild subgroups may have been better explained as an ADHD symptom severity effect. There was also evidence of a five-subgroup solution, in which cognitive measures differentiated the Surgent subgroup into those with and without cognitive impairment. Cognitive measures also appeared to differentiate the Irritable subgroup based on severity, although differences in resulting subgroups appeared better explained via differences in negative affect and shyness. Subgroups within the five-subgroup solution meaningfully differed with respect to concurrent comorbidity. The utility of the five-subgroup solution for predicting comorbid diagnoses 2 years later was more limited. Additional work is needed to fully characterize the integration of cognitive and affective functioning in ADHD and their overlapping or additive value for clinical prediction.

Conceptualizing the UPPS-P model of impulsive personality through network analysis: Key dimensions and general robustness across young adulthood.

OBJECTIVE: Within the UPPS-P model of impulsive personality, negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking dimensions have been linked to unique etiological mechanisms and outcomes. Yet, additional research is needed exploring direct relations among dimensions to determine how these relations may contribute to the nature of impulsive personality and its correlates. The current study used network analysis to clarify relations among UPPS-P dimensions and assess global robustness of these relations across young adulthood. METHOD: Participants included a longitudinal sample of 525 college students (48% male, 18-26 years) who completed the UPPS-P once per year for three consecutive years. RESULTS: Network structure was globally robust with particularly strong relations emerging between positive and negative urgency, as well as between lack of premeditation and lack of perseverance, across waves. Lack of premeditation consistently emerged as a central dimension. Additional analyses suggested lack of premeditation and sensation seeking as most robustly related with retrospectively reported frequency of alcohol use. CONCLUSIONS: Results suggested general robustness in the relations among impulsive personality dimensions, with relations involving lack of premeditation being particularly important for characterizing impulsive personality's nature. Sensation seeking and lack of premeditation may warrant particular focus when linking impulsive personality with frequency of alcohol use.

Global coagulation assays in hemophilia A: A comparison to conventional assays.

BACKGROUND: Global assays measure the interactions of coagulants, anticoagulants, and platelets on thrombin generation and may reflect the comprehensive coagulation potential in patients with hemophilia better than conventional assays. OBJECTIVES: The objectives of the current study were to investigate the value of global assays for measuring and monitoring the coagulation potential of patients with hemophilia A (HA). PATIENTS/METHODS: Rotational thromboelastometry, thrombin generation assay (TGA), and activated partial thromboplastin time (APTT) clot waveform analysis were investigated in a cohort of patients with severe, moderate, and mild HA and compared with conventional assays. RESULTS: The maximum velocity (MaxVel) parameter of modified thromboelastometry analysis, initiated by tissue factor and in the presence of corn trypsin inhibitor (CTI), had 92% sensitivity and 95% specificity for hemophilia diagnosis. The MaxVel also strongly correlated with factor VIII (FVIII) levels of patients with HA (r = .805, P < .0001). CTI improved the sensitivity of TGA, providing more accurate results. In particular, peak height parameter of platelet-rich plasma samples with CTI had a sensitivity and specificity of 100% and 94%, respectively, in all patients with HA. APTT clot waveform analysis minimum value of first derivative (Min1) and minimum value of second derivative (Min2) parameters (representing speed and acceleration of clot formation, respectively) were sensitive and correlated more strongly with FVIII levels than APTT clotting times did (Min1: r = 0.786, P < 0.0001; Min2: r = 0.759, P < 0.0001; APTT: r = -0.513, P = 0.001). CONCLUSIONS: The sensitivity and specificity of the global assays was method dependent. Correlation between clinical end points and thrombin generation might also be valuable in the era of non-factor replacement therapy.

Conceptualizing Callous-Unemotional Traits in Preschool through Confirmatory Factor and Network Analysis.

Callous - unemotional (CU) traits are a key factor in understanding the persistence and severity of conduct problems. Most research has used confirmatory factor analysis (CFA) to examine the structure of CU traits; however, most CFA models have yielded marginally acceptable fit, and little research has examined the structure of CU traits in preschool. This gap highlights the need for a more nuanced approach in understanding the structure of CU traits during preschool via statistical examination of inter - item relationships (i.e., network analysis). Therefore, the current study used both CFA and network analysis in a sample of 104 preschool children (M age = 4.76). CFA results best supported a two - factor structure of the ICU, comprised of callous and uncaring factors, using 12 of the original 24 items from the ICU, although fit was only marginally acceptable. Network community analyses identified four clusters of items characterized as Uncaring, Lack of Remorse, Unconcerned, and Callous. Items identified as most central to the network were: Does not care who he/she hurts to get what they want, Does not care if he/she is in trouble, and Seems very cold and uncaring. Overall, network analysis suggests several important potential refinements to CU structure including possible alternative factor models which merit consideration in future work. In addition, the identified central items could be useful for screening.

Forming first impressions of children: the role of attention-deficit/hyperactivity disorder symptoms and emotion dysregulation.

BACKGROUND: Previous research on peer status of children with attention-deficit/hyperactivity disorder (ADHD) has focused on already-established peer groups, rendering the specific social behaviors that influence peers' initial impressions largely unknown. Recently, theorists have argued that emotion dysregulation is a key aspect of ADHD, with empirical work finding relations between emotion dysregulation and social outcomes. Therefore, the current study focuses on the initial interactions among children varying in ADHD symptoms duringh a novel playgroup, proposing that emotion dysregulation displayed during the playgroup may serve as a possible pathway between ADHD symptoms and peers' initial negative impressions. METHODS: Participants were 233 elementary-age children ranging from 8 to 10 years old (M = 8.83, 70% male). Parents and teachers rated children's ADHD symptoms and related impairment; 51% of the children met criteria for an ADHD diagnosis. Then, children participated with unfamiliar peers in a three-hour playgroup that included three structured and two unstructured tasks. After the tasks, children and staff rated each child on social outcomes. Coders unaware of child's diagnostic status watched videos of the groups and rated each child's global emotion dysregulation during each task. RESULTS: Using multiple raters and methods, ADHD severity was associated with more negative peer ratings, through observed emotion dysregulation. Results were consistent for both parent and teacher ratings of ADHD severity as well as for both peer ratings of likeability and staff ratings of perceived peer likeability. CONCLUSIONS: When focusing on improving peers' initial impressions of children with ADHD symptoms, emotion dysregulation may be a valuable target for intervention.

Longitudinal and reciprocal relations between delay discounting and crime.

Theorists argue that self-control failure is the underlying cause of criminal behavior, with previous research linking poor self-control to delinquency and drug use. The path from self-control to crime is well-established, but less is known about whether criminal behavior contributes to self-control deficits over time. We investigated bi-directional relations between self-control assessed via a delay discounting task and self-reported crime over a three-year period. During their first, second (73.38% retention rate), and third (63.12% retention rate) years of college, 526 undergraduates completed a delay discounting task and reported on their criminal behavior. In order to maximize variability, participants with conduct problems were overrecruited, comprising 23.1% of the final sample. As expected, more discounting of hypothetical monetary rewards significantly predicted future property crime across a one and two-year period, even when controlling for initial levels of both. This study also demonstrated evidence of a bi-directional relationship; violent crime predicted higher rates of delay discounting one year later. These results suggest that bi-directional relations exist between self-control and types of crime.

Cross-lagged relations between motives and substance use: Can use strengthen your motivation over time?

Motives for substance use have garnered considerable attention due to the strong predictive utility of this construct, both in terms of use and problems associated with use. The current study examined the cross-lagged relations between alcohol use and motives, and marijuana use and motives over three yearly assessment periods in a large sample (N=526, 48% male) of college students. The relations between substance use and motives were assessed at each time point, allowing for the examination of these inter-relations over time. Results indicated different trends based on the type of substance. For alcohol use, cross-lagged trends were found between freshman and sophomore year for coping, social, and conformity motives with cross-lagged relations between enhancement motives and alcohol use across all years. However, outside of enhancement motives, cross-lagged relations were not found between sophomore and junior year. In contrast, cross-lagged effects were found for marijuana use and coping, enhancement, and expansion motives between sophomore and junior year, but not freshman year. These results suggest that people's expectations that drinking or smoking marijuana makes activities more reinforcing and helps them cope with distress may perpetuate use. In turn, use itself may enhance these expectations over time. Results have direct implications for treatment, with recommended focus on motives, behavior activation, and healthy coping skills in order to interrupt the cycle of substance use.

Impulsivity Symptoms as Core to the Developmental Externalizing Spectrum.

Impulsivity is posited to be a key part of the externalizing spectrum during childhood, but this idea has received minimal empirical attention. The goal of the present investigation was to utilize network analysis to determine whether behavioral impulsivity symptoms are key components of the externalizing network across several developmental periods from preschool into adolescence. Participants were 109 preschoolers (64 % male) ages 3 to 6, 237 children (59 % male) ages 6 to 9, 372 children (59 % male) ages 10 to 13, and 357 adolescents (59 % male) ages 13 to 17 and their parents. Parents completed ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) symptoms on a well-validated rating scale. Network analyses indicated that ADHD and ODD were somewhat differentiated in preschool, becoming united by behavioral impulsivity symptoms during early childhood, and then differentiating into inattention versus externalizing clusters later during childhood and in adolescence. Behavioral impulsivity symptoms were core to the externalizing spectrum across most developmental periods, but core inattentive and ODD symptoms were also identified in line with progressive differentiation. These results suggest the increasing importance of impulsivity symptoms across development, explaining externalizing comorbidity and potentially serving as a viable target for childhood interventions for externalizing problems.

ODD Symptom Network during Preschool.

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- cluster solutions of ODD, but perhaps provide most support for the three-cluster solution. In addition, results support the idea that negative affect, particularly anger, forms the core of the ODD symptom network during preschool. These results suggest the importance of targeting anger in preschool interventions for ODD.

Inherited bleeding disorders in older women.

Inherited bleeding disorders (IBDs) are by definition life-long. The commonest IBD is von Willebrand disease (VWD), a deficiency of von Willebrand factor (VWF), with a prevalence 1% in the general population and 13% in women with menorrhagia. Other IBDs include carriers of haemophilia A (factor VIII deficiency) and haemophilia B, (factor IX deficiency) and rare bleeding disorders (RBDs), deficiencies of factors XI, X, V, VII, II, I and inherited platelet disorders. Diagnosis is the synthesis of a bleeding history, family history and specialised laboratory tests. Women with IBDs are more likely to suffer HMB, to be symptomatic, and to present with bleeding in association with gynaecological problems. Heavy and/or abnormal menstrual bleeding increases with age due increased anovulatory cycles and gynaecological pathologies in older women. Thus, older women with IBDs are more likely to present with gynaecological bleeding symptoms, have impaired QOL and require surgical interventions. Treatment with specific clotting factor concentrates may be required and this requires an expert in haematology. Awareness of IBDs among health care providers, early diagnosis and appropriate management in a multidisciplinary approach is required to minimise the bleeding complications for women with IBDs.

Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel.

Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherited bleeding disorders and recent guidance for optimal management is lacking. Following a comprehensive review of the literature, an international expert panel in obstetrics, gynecology and hematology reached consensus on recommendations regarding the management of acute menorrhagia in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease, platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute menorrhagia are discussed and special consideration is given for the treatment of women on anticoagulation therapy. This review and accompanying recommendations will provide guidance for healthcare practitioners in the emergency management of acute menorrhagia.

Puerperal loss (lochia) in women with or without inherited bleeding disorders.

OBJECTIVE: To assess the quantity and duration of lochia in women with or without inherited bleeding disorders and to identify factors that influence lochial loss. STUDY DESIGN: Pictorial blood assessment chart was completed by 115 pregnant women (21 with or carriers of inherited bleeding disorder and 94 without bleeding disorder) using standardized sanitary products. RESULTS: The median duration of lochia was significantly longer in women with (or carriers of) inherited bleeding disorder (39 days; range 21-58) compared with women without bleeding disorder (31 days; range, 10-62; P = .03); however, the median lochial loss were similar (441 mL; range, 135-1290 vs 429 mL; range, 112-1295; P = .59). Long labor and instrumental delivery were associated with heavier lochia. CONCLUSION: Pictorial blood assessment chart is potentially a useful tool in the assessment of lochia. Women with inherited bleeding disorders experience longer period of lochia compared with women without bleeding disorder. Labor duration and mode of delivery influence lochial loss.