Recombinant factor IX-Fc fusion protein in severe hemophilia B: Patient-reported outcomes and health-related quality of life.

INTRODUCTION: In 2017, all people with severe hemophilia B in Ireland switched to recombinant factor IX Fc fusion protein concentrate (rFIXFc) prophylaxis. Patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are important to evaluate with new treatments. AIMS: To assess HRQoL in people with severe hemophilia B and their experience after switching to rFIXFc prophylaxis. METHODS: Participants completed a Patient Reported Outcomes Burden and Experience (PROBE) questionnaire on initiation and following two years of rFIXFc prophylaxis. The PROBE questionnaire has four domains: demographics, general health, haemophilia-specific, and European Quality of Life 5-Dimensions (EQ-5D-5L) questionnaire. RESULTS: Twenty-three participants completed the questionnaire at both time points. The number of activities where chronic pain occurred and interfered with the activity was reduced by 25% and 33%, respectively (P < .001), following two years of rFIXFc prophylaxis. There was a 9% decrease in chronic pain during the second year of rFIXFc prophylaxis compared to baseline, but the rate remained high, at 74%. A 25% reduction in the number of affected activities of daily living (ADLs) was reported following 2 years of rFIXFc prophylaxis (P = .007). The most common health problems were arthritis, hypertension, anxiety/depression, and gingivitis. The median EQ-5D-5L score was similar following two years of rFIXFc prophylaxis, 0.76 (range, -0.01 to 0.95), compared to 0.77 (range, 0.36-1) at baseline. CONCLUSION: This study of real-world patient experience using PROs demonstrates a reduction in chronic pain and improvement in ADLs in participants after switching to rFIXFc prophylaxis. It provides important insights into patient-identified health care needs and living with severe hemophilia B.

Executive Function: Cognition and Behaviour in Adults with Autism Spectrum Disorders (ASD).

Studies of executive function (EF) in autism spectrum disorder (ASD) have reported mixed findings. Possible confounds include EF domain assessed and co-occurring neurodevelopmental diagnoses. EF task performance across multiple domains and everyday function of autistic adults (n = 110) was significantly different to age- and IQ-matched controls (n = 31). Although significantly more likely to fall into the clinically impaired range, 35.8% of the ASD group showed no impairment on EF measures. Factor analysis revealed a single unifying EF construct rather than a selective pattern of impairment. Dysexecutive behaviours were frequently reported in the ASD group, unrelated to Autism symptoms, EF task performance or co-occurring conditions. This study suggests autistic adults can experience clinically significant executive function difficulties and co-occuring dysexecutive behaviours that are disabling in everyday life.

Large mammal declines and the incipient loss of mammal-bird mutualisms in an African savanna ecosystem.

Over the past half-century, large mammal populations have declined substantially throughout East Africa, mainly due to habitat loss and unsustainable direct exploitation. While it has been acknowledged that the loss of large mammals can have direct and cascading effects on community composition and ecosystem characteristics, limited quantitative work has been done on how declines of large herbivore populations impacts the abundance of mutualistic symbionts. Using a space-for-time observational approach, we quantified the large mammal community alongside the densities, host preferences and behaviors of mutualistic red-billed oxpeckers (Buphagus erythrorhynchus), and yellow-billed oxpeckers (Buphagus africanus) in northern Tanzania. At the landscape scale, mammal community composition was substantially less diverse in highly human-dominated areas when compared with more protected areas, with an observed complete loss of large wild mammal species in two study areas. Mirroring this trend, oxpecker densities were lowest in the least protected areas, and highest in fully protected areas. Using resource selection functions implemented via generalized linear models at different scales, we found that oxpeckers (1) were predominantly (67% of red-billed oxpeckers; 70% of yellow-billed oxpeckers) feeding on larger (between 500kg and 1500kg) ungulate host species within the mammal community, (2) usually preferred feeding on larger individuals (adults and males) within a specific host species population, and (3) preferred hosts that were more tolerant of their presence. In particular, cattle were especially intolerant of oxpecker presence and were relatively effective in displacing oxpeckers. We found little evidence that oxpecker feeding was parasitic across all host species; wound feeding was only observed on giraffe, comprising 6% and 4% of feeding behavior in red-billed and yellow-billed oxpeckers respectively. Thus, a loss of large-bodied and oxpecker tolerant host species is a likely explanation for declines of oxpecker populations in human dominated landscapes, which may have further cascading effects.

Does Talking on a Cell Phone, With a Passenger, or Dialing Affect Driving Performance? An Updated Systematic Review and Meta-Analysis of Experimental Studies.

Objective An up-to-date meta-analysis of experimental research on talking and driving is needed to provide a comprehensive, empirical, and credible basis for policy, legislation, countermeasures, and future research. Background The effects of cell, mobile, and smart phone use on driving safety continues to be a contentious societal issue. Method All available studies that measured the effects of cell phone use on driving were identified through a variety of search methods and databases. A total of 93 studies containing 106 experiments met the inclusion criteria. Coded independent variables included conversation target (handheld, hands-free, and passenger), setting (laboratory, simulation, or on road), and conversation type (natural, cognitive task, and dialing). Coded dependent variables included reaction time, stimulus detection, lane positioning, speed, headway, eye movements, and collisions. Results The overall sample had 4,382 participants, with driver ages ranging from 14 to 84 years ( M = 25.5, SD = 5.2). Conversation on a handheld or hands-free phone resulted in performance costs when compared with baseline driving for reaction time, stimulus detection, and collisions. Passenger conversation had a similar pattern of effect sizes. Dialing while driving had large performance costs for many variables. Conclusion This meta-analysis found that cell phone and passenger conversation produced moderate performance costs. Drivers minimally compensated while conversing on a cell phone by increasing headway or reducing speed. A number of additional meta-analytic questions are discussed. Application The results can be used to guide legislation, policy, countermeasures, and future research.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition.

A new test of advanced theory of mind: The "Strange Stories Film Task" captures social processing differences in adults with autism spectrum disorders.

Real-life social processing abilities of adults with autism spectrum disorders (ASD) can be hard to capture in lab-based experimental tasks. A novel measure of social cognition, the "Strange Stories Film task' (SSFt), was designed to overcome limitations of available measures in the field. Brief films were made based on the scenarios from the Strange Stories task (Happé) and designed to capture the subtle social-cognitive difficulties observed in ASD adults. Twenty neurotypical adults were recruited to pilot the new measure. A final test set was produced and administered to a group of 20 adults with ASD and 20 matched controls, alongside established social cognition tasks and questionnaire measures of empathy, alexithymia and ASD traits. The SSFt was more effective than existing measures at differentiating the ASD group from the control group. In the ASD group, the SSFt was associated with the Strange Stories task. The SSFt is a potentially useful tool to identify social cognitive dis/abilities in ASD, with preliminary evidence of adequate convergent validity. Future research directions are discussed. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1120-1132. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

The mental health of individuals referred for assessment of autism spectrum disorder in adulthood: A clinic report.

Growing awareness of autism spectrum disorders has increased the demand for diagnostic services in adulthood. High rates of mental health problems have been reported in young people and adults with autism spectrum disorder. However, sampling and methodological issues mean prevalence estimates and conclusions about specificity in psychiatric co-morbidity in autism spectrum disorder remain unclear. A retrospective case review of 859 adults referred for assessment of autism spectrum disorder compares International Classification of Diseases, Tenth Revision diagnoses in those that met criteria for autism spectrum disorder (n = 474) with those that did not (n = 385). Rates of psychiatric diagnosis (>57%) were equivalent across both groups and exceeded general population rates for a number of conditions. The prevalence of anxiety disorders, particularly obsessive compulsive disorder, was significantly higher in adults with autism spectrum disorder than adults without autism spectrum disorder. Limitations of this observational clinic study, which may impact generalisability of the findings, include the lack of standardised structured psychiatric diagnostic assessments by assessors blind to autism spectrum disorder diagnosis and inter-rater reliability. The implications of this study highlight the need for careful consideration of mental health needs in all adults referred for autism spectrum disorder diagnosis.

A meta-analysis of the effects of texting on driving.

Text messaging while driving is considered dangerous and known to produce injuries and fatalities. However, the effects of text messaging on driving performance have not been synthesized or summarily estimated. All available experimental studies that measured the effects of text messaging on driving were identified through database searches using variants of "driving" and "texting" without restriction on year of publication through March 2014. Of the 1476 abstracts reviewed, 82 met general inclusion criteria. Of these, 28 studies were found to sufficiently compare reading or typing text messages while driving with a control or baseline condition. Independent variables (text-messaging tasks) were coded as typing, reading, or a combination of both. Dependent variables included eye movements, stimulus detection, reaction time, collisions, lane positioning, speed and headway. Statistics were extracted from studies to compute effect sizes (rc). A total sample of 977 participants from 28 experimental studies yielded 234 effect size estimates of the relationships among independent and dependent variables. Typing and reading text messages while driving adversely affected eye movements, stimulus detection, reaction time, collisions, lane positioning, speed and headway. Typing text messages alone produced similar decrements as typing and reading, whereas reading alone had smaller decrements over fewer dependent variables. Typing and reading text messages affects drivers' capability to adequately direct attention to the roadway, respond to important traffic events, control a vehicle within a lane and maintain speed and headway. This meta-analysis provides convergent evidence that texting compromises the safety of the driver, passengers and other road users. Combined efforts, including legislation, enforcement, blocking technologies, parent modeling, social media, social norms and education, will be required to prevent continued deaths and injuries from texting and driving.

Attention deficit hyperactivity disorder symptoms in adults with autism spectrum disorders.

Features of attention deficit hyperactivity disorder (ADHD) and impairments on neuropsychological, tests of attention have been documented in children with autism spectrum disorders (ASDs). To date, there has been a lack of research comparing attention in adults with ASD and adults with ADHD. In study 1, 31 adults with ASD and average intellectual function completed self-report measures of ADHD symptoms. These were compared with self-report measures of ADHD symptoms in 38 adults with ADHD and 29 general population controls. In study 2, 28 adults with a diagnosis of ASD were compared with an age- and intelligence quotient-matched sample of 28 adults with ADHD across a range of measures of attention. Study 1 showed that 36.7% of adults with ASD met Diagnostic and Statistical Manual-IV criteria for current ADHD "caseness" (Barkley Current self-report scores questionnaire). Those with a diagnosis of pervasive developmental disorder-not otherwise specified were most likely to describe ADHD symptoms. The ASD group differed significantly from both the ADHD and control groups on total and individual symptom self-report scores. On neuropsychological testing, adults with ASD and ADHD showed comparable performance on tests of selective attention. Significant group differences were seen on measures of attentional switching; adults with ADHD were significantly faster and more inaccurate, and individuals with Asperger's syndrome showed a significantly slower and more accurate response style. Self-reported rates of ADHD among adults with ASD are significantly higher than in the general adult population and may be underdiagnosed. Adults with ASD have attentional difficulties on some neuropsychological measures.

Cognitive behavior therapy for comorbid obsessive-compulsive disorder in high-functioning autism spectrum disorders: a randomized controlled trial.

BACKGROUND: High rates of anxiety disorders, particularly obsessive compulsive disorder (OCD) are reported in people with Autism spectrum disorders (ASD). Group cognitive behavioral treatment (CBT) has been found effective for anxiety in young people with ASD but not been OCD specific. One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy. METHODS: Forty-six adolescents and adults (mean age 26.9 years, 35 Males) with ASD and comorbid OCD were randomized to CBT for OCD or anxiety management (AM), a plausible control treatment. Treatments were matched in duration (mean of 17.4 sessions CBT; 14.4 sessions AM), the Yale-Brown Obsessive Compulsive Severity Scale (YBOCS) as primary outcome measure and evaluations blind to treatment group. Treatment response was defined as > 25% reduction in YBOCS total severity scores. RESULTS: Both treatments produced a significant reduction in OCD symptoms, within-group effect sizes of 1.01 CBT group and 0.6 for the AM group. There were no statistically significant differences between the two groups at end of treatment, although more responders in the CBT group (45 versus 20%). Effect sizes for self-rated improvement were small (0.33 CBT group; -0.05 AM group). Mild symptom severity was associated with improvement in the AM but not the CBT group. Family/carer factors were important for both groups, in that increased family accommodation was associated with poorer outcome. CONCLUSIONS: Evidence-based psychological interventions, both AM and CBT, were effective in treating comorbid OCD in young people and adults with ASD.

Response inhibition in adults with autism spectrum disorder compared to attention deficit/hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are hypothesised to involve core deficits in executive function. Previous studies have found evidence of a double dissociation between the disorders on specific executive functions (planning and response inhibition). To date most research has been conducted with children. No studies have directly compared the stable cognitive profile of adults. It was hypothesised that adults with ASD would show generally intact response inhibition whereas those with ADHD would show more global impairment. Participants were 24 adults aged 18-55 with high functioning ASD, 24 with ADHD, and 14 age and IQ matched controls. Participants completed three standardised measures of response inhibition. Participants with ASD had generally intact response inhibition but slow response latencies, possibly due to deficits in response initiation. Adults with ADHD did not show the more global impairments hypothesised. There were some significant differences between the clinical groups across measures of inhibition. In terms of performance style, adults with ASD were slow and accurate whilst those with ADHD showed an impulsive style.

Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia.

OBJECTIVE: The authors systematically reviewed the literature on psychological approaches to treating the neuropsychiatric symptoms of dementia. METHOD: Reports of studies that examined effects of any therapy derived from a psychological approach that satisfied prespecified criteria were reviewed. Data were extracted, the quality of each study was rated, and an overall rating was given to each study by using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: A total of 1,632 studies were identified, and 162 satisfied the inclusion criteria for the review. Specific types of psychoeducation for caregivers about managing neuropsychiatric symptoms were effective treatments whose benefits lasted for months, but other caregiver interventions were not. Behavioral management techniques that are centered on individual patients' behavior or on caregiver behavior had similar benefits, as did cognitive stimulation. Music therapy and Snoezelen, and possibly sensory stimulation, were useful during the treatment session but had no longer-term effects; interventions that changed the visual environment looked promising, but more research is needed. CONCLUSIONS: Only behavior management therapies, specific types of caregiver and residential care staff education, and possibly cognitive stimulation appear to have lasting effectiveness for the management of dementia-associated neuropsychiatric symptoms. Lack of evidence regarding other therapies is not evidence of lack of efficacy. Conclusions are limited because of the paucity of high-quality research (only nine level-1 studies were identified). More high-quality investigation is needed.

The TE4D-Cog: a new test for detecting early dementia in English-speaking populations.

BACKGROUND: The screening test usually used to detect dementia (Mini Mental State Examination, MMSE) is limited by a ceiling effect and high false positive rates, as are other similar instruments. There is therefore a need for a more sensitive and specific screening tool to aid early detection and diagnosis of dementia. OBJECTIVE: The hypothesis of the study was that the TE4D-Cog would be more sensitive and specific than the MMSE in detecting mild cognitive impairment in patients with AD. METHOD: The TE4D (Test for the Early Detection of Dementia from Depression) was adapted from its original German version for English-speaking populations. This new scale (the TE4D-Cog) was then administered together with the MMSE and the cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS-Cog) to 178 people with a diagnosis of Alzheimer's disease and 25 cognitively intact comparators. The sensitivity and specificity in detecting dementia of the TE4D-Cog and the MMSE were compared in those with mild dementia and those without dementia. RESULTS: The TE4D-cog had high sensitivity with an acceptable specificity and low false positive rate. It also had good concurrent validity, high inter-rater reliability, good internal consistency and strong predictive validity. CONCLUSIONS: The TE4D-Cog is easy to administer, short and acceptable. Results are independent of age, gender and level of education. The TE4D-Cog may therefore be a useful alternative to the MMSE as a dementia screening instrument.

A comparison of cochlear implant processing strategies in children using speech pattern audiometry.

The aim of this study was to use Speech Pattern Audiometry (SPA) to compare phoneme perception performance between SPEAK and ACE processing strategies with children using the Nucleus 24 cochlear implant. Listeners were evaluated in terms of ability to identify two synthetic word pairs, one signalling a voicing contrast and the other signalling a place of articulation contrast. For both word pairs, ACE was associated with more 'normal' phoneme boundaries than SPEAK. There was also a non-significant trend for better identification ability with ACE compared to SPEAK. The study suggests that there may be a place for SPA as part of the clinical battery of tests used for evaluation of cochlear implant speech processing strategies in children. Copyright (c) 2005 John Wiley & Sons, Ltd.

Prototype demonstration of transgenic resistance to the nematode Radopholus similis conferred on banana by a cystatin.

Cavendish banana was transformed using Agrobacterium tumefaciens to express a protein engineered rice cystatin (OcIdeltaD86) of value for control of plant parasitic nematodes. Expression for each line was under control of a constitutive promoter from the maize ubiquitin gene (UBI-1), a constitutive, chimeric promoter from the octopine and mannopine synthase genes of A. tumefaciens or a promoter from a root-preferentially expressed tubulin gene Arabidopsis (TUB-1). Lines were selected as of potential interest after 8 weeks challenge in containment if their mean R. similis/25 g roots for three sibling plants were more than 1 standard normal variate below the grand mean for all plants in c7-15 lines challenged concurrently. A total of 16 lines were selected on this basis as putative positives. Western blots confirmed that eight of these lines expressed cystatin with a mean of 0.08 +/- 0.04% tsp. All but two of 19 negatively selected lines from bioassays did not express cystatin. The mean resistance level of the confirmed positive lines was 69 +/- 17%. ELISA established the positive lines under control of UBI provided significantly higher expression levels of OcIdeltaD86 than recorded for the other two promoters. Lines of interest were confirmed as producing a transcript for OcIdeltaD86 by RT-PCR. Eight plants of one UBI promoter line expressing only 0.1 +/- 0.004% tsp as cystatin were re-challenged with R. similis and achieved a resistance of 70 +/- 10%. Subsequent repeat western blotting confirmed that this line still produced the cystatin after the trial. This is the first report of transgenic resistance against a major pest or disease of banana.

What causes problems in Alzheimer's disease: attributions by caregivers. A qualitative study.

OBJECTIVE: To gain insight into caregivers' understanding of the causes of behaviours they find problematic in people with Alzheimer's disease in order to inform the development of educational strategies. METHODS: A qualitative, semi-structured interview was used. Participants were 205 caregivers for a person with Alzheimer's disease, all of whom were aware of the diagnosis and who had been recruited as part of a larger longitudinal study. Participants were from inner-city and suburban London/semi-rural Essex. The main outcome measures were caregivers' understanding of: the cause of problematic behaviour; the ability of the person with dementia to control this behaviour; the prognosis of the illness. RESULTS: Most carers attribute the cognitive, behavioural and psychological symptoms of dementia to causes other than dementia; many believe that the person with dementia has control over their behaviour and substantial numbers believe the person with dementia will return to normal. CONCLUSIONS: This study suggests that providing facts about the illness to caregivers is not enough, as caregivers may not understand that the symptoms they observe are related to the diagnosis. Education by clinicians should focus on the understanding of caregivers and in particular explore the caregivers' attributions of the symptoms which are present in the person for whom they care.