Prospective Validation of the Emergency Heart Failure Mortality Risk Grade for Acute Heart Failure.

BACKGROUND: Improved risk stratification of acute heart failure in the emergency department may inform physicians' decisions regarding patient admission or early discharge disposition. We aimed to validate the previously-derived Emergency Heart failure Mortality Risk Grade for 7-day (EHMRG7) and 30-day (EHMRG30-ST) mortality. METHODS: We conducted a multicenter, prospective validation study of patients with acute heart failure at 9 hospitals. We surveyed physicians for their estimates of 7-day mortality risk, obtained for each patient before knowledge of the model predictions, and compared these with EHMRG7 for discrimination and net reclassification improvement. We also prospectively examined discrimination of the EHMRG30-ST model, which incorporates all components of EHMRG7 as well as the presence of ST-depression on the 12-lead ECG. RESULTS: We recruited 1983 patients seeking emergency department care for acute heart failure. Mortality rates at 7 days in the 5 risk groups (very low, low, intermediate, high, and very high risk) were 0%, 0%, 0.6%, 1.9%, and 3.9%, respectively. At 30 days, the corresponding mortality rates were 0%, 1.9%, 3.9%, 5.9%, and 14.3%. Compared with physician-estimated risk of 7-day mortality (PER7; c-statistic, 0.71; 95% CI, 0.64-0.78) there was improved discrimination with EHMRG7 (c-statistic, 0.81; 95% CI, 0.75-0.87; P=0.022 versus PER7) and with EHMRG7 combined with physicians' estimates (c-statistic, 0.82; 95% CI, 0.76-0.88; P=0.003 versus PER7). Model discrimination increased nonsignificantly by 0.014 (95% CI, -0.009-0.037) when physicians' estimates combined with EHMRG7 were compared with EHMRG7 alone ( P=0.242). The c-statistic for EHMRG30-ST alone was 0.77 (95% CI, 0.73-0.81) and 30-day model discrimination increased nonsignificantly by addition of physician-estimated risk to 0.78 (95% CI, 0.73-0.82; P=0.187). Net reclassification improvement with EHMRG7 was 0.763 (95% CI, 0.465-1.062) when assessed continuously and 0.820 (0.560-1.080) using risk categories compared with PER7. CONCLUSIONS: A clinical model allowing simultaneous prediction of mortality at both 7 and 30 days identified acute heart failure patients with a low risk of events. Compared with physicians' estimates, our multivariable model was better able to predict 7-day mortality and may guide clinical decisions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02634762.

Making Informed CHOICES: The Launch of a "Big Data" Pragmatic Trial to Improve Cholesterol Management and Prevent Heart Disease in Ontario.

Cholesterol-lowering statin medications are a safe and effective therapy to lower cholesterol and reduce the risk of cardiovascular events. Yet physician prescribing patterns and patient adherence remain suboptimal in Canada and the United States, often due to pervasive misconceptions. The Community Heart Outcomes Improvement and Cholesterol Education Study (CHOICES) is a pragmatic, registry-based, cluster randomized controlled trial that aims to improve cholesterol management through appropriate statin use in adults and to ultimately reduce cardiovascular events in high-risk communities across Ontario. The trial uses an innovative, multicomponent intervention and implementation approach that includes audit and feedback reports for family physicians and educational materials and tools for patients.

Designing Developmentally Sensitive AAC Technologies for Young Children with Complex Communication Needs: Considerations of Communication, Working Memory, Attention, Motor Skills, and Sensory-Perception.

Young children who require augmentative and alternative communication (AAC) must be provided with AAC technologies that are designed to meet their needs and accommodate their skills. One critical aspect of matching the system design features of aided AAC technologies to the needs and abilities of the child with complex communication needs is a consideration of the child's developmental skills. This article provides an overview of specific, early developmental milestones in communication, cognition (i.e., attention and working memory), motor skills, and sensory-perception (including visual attention) that influence decisions regarding AAC system design for young children. Developmental considerations are also reviewed for young children with Down's syndrome, a group that often benefits from early provision of AAC. Based on developmental theory and milestones, specific recommendations are provided for the design of developmentally sensitive AAC technologies for young children who are beginning communicators.

Preliminary investigation of visual attention to complex AAC visual scene displays in individuals with and without developmental disabilities.

Visual scene displays (VSDs) are one type of augmentative and alternative communication (AAC) display in which an integrated scene (typically a photograph) presents people engaged in shared activities, with "hotspots" for the concepts embedded within. Most AAC displays are more complex than a single VSD, and also contain a navigation bar. This preliminary study examined visual attention to these more complex AAC displays by participants with autism spectrum disorder (ASD) (n = 13), Down syndrome (n = 13), intellectual and developmental disabilities other than Down syndrome or ASD (n = 9), and preschoolers with typical development (n = 20). Participants viewed images that simulated complex AAC displays containing a main VSD and a navigation bar with thumbnail VSDs arranged in one of four locations (top, bottom, left, or right). Both the main VSD and the navigation bar attracted attention, with participants across groups looking at both elements more than expected based on the space those elements occupied within the display. Within the main VSD, participants spent more time fixating on the meaningful elements (i.e., children and shared activity) compared to the background. Results suggested that gaze patterns to the meaningful elements of the main VSD were influenced by the location of the navigation bar. The finding that bar location may influence visual attention patterns makes it an important AAC system design factor that warrants additional research.

A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer.

BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer. METHODS: In this phase I dose-escalation study, patients with trastuzumab-resistant HER2-positive metastatic breast cancer received weekly trastuzumab (2 mg/kg) and paclitaxel (80 mg/m2) on days 1, 8, 15, and 22 of a 28-day cycle with escalating doses of ganetespib (100 mg/m2, 150 mg/m2, and a third cohort of 125 mg/m2 if needed) on days 1, 8, and 15. Therapy was continued until disease progression or toxicity. The primary objective was to establish the safety and maximum tolerated dose and/or recommended phase II dose (RP2D) of this therapy. The secondary objectives included evaluation of the effects of ganetespib on the pharmacokinetics of paclitaxel, and to make a preliminary assessment of the efficacy of the combination therapy. RESULTS: Dose escalation was completed for the two main cohorts without any observed dose-limiting toxicities. Nine patients received treatment. The median prior lines of anti-HER2 therapy numbered three (range 2-4), including prior pertuzumab in 9/9 patients and ado-trastuzumab emtansine (T-DM1) in 8/9 patients. The most common grade 1/2 adverse events (AEs) were diarrhea, fatigue, anemia, and rash. There were no grade 4 AEs related to ganetespib. The overall response rate was 22% (2/9 patients had partial response) and stable disease was seen in 56% (5/9 patients). The clinical benefit rate was 44% (4/9 patients). The median progression-free survival was 20 weeks (range 8-55). CONCLUSION: The RP2D of ganetespib is 150 mg/m2 in combination with weekly paclitaxel plus trastuzumab. The combination was safe and well tolerated. Despite prior taxanes, pertuzumab, and T-DM1, clinical activity of this triplet regimen in this heavily pretreated cohort is promising and warrants further study in HER2-positive metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02060253 . Registered 30 January 2014.

Bridging the gap from values to actions: a family systems framework for family-centered AAC services.

Despite the growing recognition of the importance of family involvement in augmentative and alternative communication (AAC) intervention, little guidance exists on how professionals can establish successful collaborative relationships with families. In this paper, we discuss family systems theory and ecological systems theory as a framework to guide family-centered AAC practice, review family-focused research in AAC, consider how AAC may impact the family system, and provide examples of the clinical implications of using the proposed family systems framework to improve family-centered AAC practice.

The sexually dimorphic behaviour of adult Drosophila suzukii: elevated female locomotor activity and loss of siesta is a post-mating response.

The polyphagous Drosophila suzukii is a highly invasive species that causes extensive damage to a wide range of berry and stone fruit crops. A better understanding of its biology and especially its behaviour will aid the development of new control strategies. We investigated the locomotor behaviour of D. suzukii in a semi-natural environment resembling a typical summer in northern England and show that adult female D. suzukii are at least 4-fold more active during daylight hours than adult males. This result was reproduced in several laboratory environments and was shown to be a robust feature of mated, but not virgin, female flies. Both males and virgin females kept on a 12 h light:12 h dark (12LD) cycle and constant temperature displayed night-time inactivity (sleep) followed by weak activity in the morning, an afternoon period of quiescence (siesta) and then a prominent evening peak of activity. Both the siesta and the sharp evening peak at lights off were severely reduced in females after mating. Flies of either sex entrained in 12LD displayed a circadian pattern of activity in constant darkness confirming the importance of an endogenous clock in regulating adult activity. This response of females to mating is similar to that elicited in female Drosophila melanogaster by the male sex peptide (SP). We used mass spectrometry to identify a molecular ion (m/z, 5145) corresponding to the poly-hydroxylated SP of D. suzukii and to show that this molecule is transferred to the female reproductive tract during copulation. We propose that the siesta experienced by male and virgin female D. suzukii is an adaptation to avoid unnecessary exposure to the afternoon sun, but that mated females faced with the challenge of obtaining resources for egg production and finding oviposition sites take greater risks, and we suggest that the change in female behaviour is induced by the male SP.

Patterns of lifetime female victimisation and psychotic experiences: a study based on the UK Adult Psychiatric Morbidity Survey 2007.

PURPOSE: Research has shown that sexual trauma represents a specific threat for psychosis, particularly among females. Sexual trauma among females, however, has also been shown to enhance the risk for further revictimisation. Females are likely to exhibit distinct lifetime trauma profiles, i.e. female sexual trauma victims are often more likely to experience particular forms of re-victimisation, such as intimate partner and domestic violence. METHODS: This study used data from the Adult Psychiatric Morbidity Survey (2007) to profile lifetime histories of sexual trauma and domestic violence among female participants (N = 4,111). RESULTS: The latent class analysis revealed four lifetime victimisation classes: (i) a multiple victimisation class; (ii) an intimate partner victimisation class; (iii) a sexual victimisation class; and (iv) a victimisation-free class. Multivariate logistic regression revealed that there was a strong association between class membership and a diagnosis of psychosis and that the victimisation classes were significantly associated with all psychotic-like experiences. Compared to the victimisation-free class, the multiple victimisation class displayed an increased likelihood of experiencing all psychotic experiences except mania. The intimate partner victimisation class was also associated with an increased likelihood of experiencing all psychotic experiences; however, the odds ratios for this class were lower than those recorded for the multiple victimisation class. CONCLUSIONS: These findings reflect female-specific variation in both victimisation history and psychosis-related vulnerability. Acknowledging such sex-specific variation may advance our understanding of the complex associations that continue to emerge between trauma and psychosis for both males and females.

Evidence for Professional Conceptualization in Science as an Important Component of Science Identity.

Experience in research facilitates development of science identity and encourages undergraduate student persistence along the pathway to careers in science, technology, engineering, and math (STEM). Participation in authentic research can foster identity development by influencing a sense of belonging, recognition, interest, and performance and competence in science. We examine science identity in a group of five community college women in marine science during a 2-year study in which students participated in a research experience. We used interviews, surveys, identity artifacts, and significant circles before and after the research experience in a thematic analysis to explore identities and examine their intentions, interests, perspectives, and aspirations for a future career. Participation in research provided opportunities for students to gain conceptual understanding of themselves and their abilities in science as well as explore and clarify their professional interests. This work builds upon our current understanding by providing evidence that conceptualization of career trajectories and self as a science professional is an important component of identity. Exploring career options and developing professional conceptualization are critical components in science research experiences and warrants additional study to understand the role of professional conceptualization in shaping student trajectories in STEM.

New psychoactives within polydrug use trajectories-evidence from a mixed-method longitudinal study.

AIMS: To provide public health-related research evidence on types and usage patterns of new psychoactive substances (NPS), developmental pathways into NPS and decision-making factors for, and associated harms of, NPS use. DESIGN: Three-phase mixed-methods design, including a latent class analysis (LCA) of the longitudinal Belfast Youth Development Study (BYDS), a narrative analysis of interviews with NPS users and a three-step approach manual method modelling using regressions to reveal classes of substance use and their associated predictors and outcomes. SETTING: Northern Ireland. PARTICIPANTS: A total of 2039 people who responded to the questions on 'ever use' of the drug variables included at wave 7 (aged 21 years) of the BYDS. Eighty-four narrative interviews with NPS users. MEASUREMENTS: Categories of drug use identified by LCA. Predictors and outcomes included measures of family, partners, peers, substance use, school, delinquency and mental health. FINDINGS: A four-class solution provided the best fit for the data: alcohol; alcohol and tobacco; alcohol, tobacco and cannabis; and polydrug (the latter including NPS). The qualitative analysis yielded a taxonomy that distinguished how NPS operate within a wider range of drug repertoires from experimental to problematic. CONCLUSIONS: In Northern Ireland, new psychoactive substances appear to be a feature of broader polydrug use rather than a standalone class of drug use.

Preliminary Investigation of the Perspectives of Parents of Children With Cerebral Palsy on the Supports, Challenges, and Realities of Integrating Augmentative and Alternative Communication Into Everyday Life.

Purpose To ensure long-term adoption and use of augmentative and alternative communication (AAC) technologies, they must be designed to support children to participate within everyday activities and routines that are prioritized by families. The aim of this study was to gain parent perspectives on how AAC technologies were integrated into everyday life. Method Nine parents of children with cerebral palsy who used AAC technologies participated in semistructured interviews to provide their perspectives on how AAC technologies were integrated into the functional contexts of everyday life. Results Five major themes emerged from the discussions: (a) integrating AAC into life, (b) AAC technologies, (c) child needs and skills, (d) parent responsibilities and priorities, and (e) AAC process and decision making. Children were able to use AAC technologies within a variety of everyday contexts with various partners; however, challenges included access to technologies within care routines and outdoor activities as well as partners who lacked knowledge regarding operational competencies and effective interaction strategies. To integrate AAC technologies into life, parents prioritized technology features including ease of programming, improved physical design, features to enhance efficiency and ease of access, and availability of multiple functions and features (e.g., games and leisure activities, environmental controls). Conclusion AAC manufacturers and mainstream technology developers should work to ensure that technologies are responsive to the supports, limitations, and ideal features identified by parents. Future research should seek input from a larger group of stakeholders and use longitudinal methods to examine perceptions of AAC technologies over time. Supplemental Material https://doi.org/10.23641/asha.11625543.

School bonding and ethos in trajectories of offending: Results from the Belfast Youth Development Study.

BACKGROUND: Aspects of the school environment, such as school attachment levels, are linked to adolescent offending. Previous research has not clarified whether a school- or individual-level intervention approach to improving pupil school attachment and commitment is most likely to reduce adolescent offending. AIM: The present study assessed the impact of individual- and school-level variables on offending behaviour from ages 14-16 years. SAMPLE: The participants were 4,049 young people from 42 mainstream schools who took part in the Belfast Youth Development Study. METHOD: Multilevel modelling was used to examine the relative influence of individual- and school-level variables on offending behaviour in adolescence. RESULTS: Pupils who had high levels of school commitment and attachment and were involved in fewer fights at age 13 reported lower levels of offending at age 14 years. Differences between schools accounted for 7% of the variation in offending. Lower individual-level commitment was associated with higher initial levels of offending at age 14 if the school-level ethos was of higher commitment. Lack of safety at the school level appeared to be detrimental for young people not exposed to socio-economic deprivation. CONCLUSIONS: Individual-level targeted interventions are likely to be a more cost-effective approach of reducing offending behaviour in adolescence. Additional, albeit smaller, reductions in offending levels could be achieved through school-level interventions in some school types (e.g., deprived areas).

Effects of Interventions That Include Aided Augmentative and Alternative Communication Input on the Communication of Individuals With Complex Communication Needs: A Meta-Analysis.

Purpose: The purpose of this meta-analysis was to investigate the effects of augmentative and alternative communication (AAC) interventions that included aided AAC input (e.g., aided AAC modeling, aided language modeling, aided language stimulation, augmented input) on communicative outcomes (both comprehension and expression) for individuals with developmental disabilities who use AAC. Method: A systematic search resulted in the identification of 26 single-case experimental designs (88 participants) and 2 group experimental designs (103 participants). Studies were coded in terms of participants, intervention characteristics, dependent variables, outcomes, and quality of evidence. Results: AAC interventions that included aided AAC input in isolation, or as part of a multicomponent intervention, were found to be highly effective across participants of various ages, disabilities, and language skills. The interventions typically included aided AAC input in conjunction with expectant delay, direct prompting (e.g., spoken, gestural), contingent responding, and open-ended questions. The interventions were found to be highly effective in supporting both comprehension and expression across the domains of pragmatics, semantics, and morphosyntax. Outcomes related to expression were reported more often than outcomes related to comprehension. Conclusion: Aided AAC input may reduce input-output asymmetry and enhance expression and comprehension for individuals who use AAC; the evidence suggests that partners should utilize this strategy. Future research is needed to investigate the effects of AAC input (aided and unaided) on long-term language development for individuals who require AAC. Supplemental Material: https://doi.org/10.23641/asha.6394364.

The prevalence of pica in tuberous sclerosis complex.

BACKGROUND: Pica and Tuberous sclerosis complex (TSC) are rare disorders. We carried out a population survey of pica in our TSC patient population. FINDINGS: Pica was identified in four percent of cases of TSC. It was associated with adult onset or persistence into adulthood, epilepsy, severe learning difficulties and anaemia. CONCLUSIONS: Pica in TSC is a rare disorder and a coherent history may be difficult to obtain from patients. The prevalence of pica is likely to be underdiagnosed. Pica is a recognised feature in adults with TSC and prompt recognition of this disorder should allow better management of patients with TSC.

Effects of age at implantation in young children.

This study examined the effects of age at implantation on the development of communication abilities in children with early implantation. The 73 participants were prelingually deafened, received a cochlear implant before 5 years of age, and used current cochlear implant technology. The children were administered a battery of speech and language outcome measures before implantation and again at successive 6-month postimplant intervals. A mixed model analysis was used to examine the rate of growth in word recognition and language skills as a function of age at time of implantation. The results revealed significant improvements in communication skills over time. Spoken word recognition improved at a faster rate in the oral children with early implantation. However, the children who underwent implantation before 3 years of age had significantly faster rates of language development than did the children with later implantation. The oral children demonstrated more rapid gains in communication abilities than did the children who used total communication.

Eye-tracking measures reveal how changes in the design of aided AAC displays influence the efficiency of locating symbols by school-age children without disabilities.

PURPOSE Many individuals with communication impairments use aided augmentative and alternative communication (AAC) systems involving letters, words, or line drawings that rely on the visual modality. It seems reasonable to suggest that display design should incorporate information about how users attend to and process visual information. The organization of AAC symbols can influence the speed and accuracy with which children select a target symbol on a display. This research examined why some displays facilitate responding. METHOD Eye-tracking technology recorded point-of-gaze while children without disabilities engaged in a visual search task with 2 AAC displays. In 1 display, symbols sharing an internal color were clustered together. In the other display, like-colored symbols were distributed. Dependent measures were (a) latency to fixate on the target compared with distracters and (b) the number of fixations to target and distracters. RESULTS Participants were significantly slower to fixate on the target when like-colored symbols were distributed; there was a significant increase in the number of fixations to distracters that did not share color with the target. CONCLUSIONS Efficient search was related to minimizing fixations to nonrelevant distracters. Vulnerability to distraction can be a significant problem in individuals with disabilities who use AAC. Minimizing the intrusion of such distraction may, therefore, be of importance in AAC display design.