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Introduction: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5–40%), moderate (1–5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. Methods: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Results: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. Conclusion: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA. [ABSTRACT FROM AUTHOR]

Background: Haemophilia A (HA; Factor VIII deficiency) is a congenital X-linked bleeding disorder characterized by trauma-related or spontaneous bleeding events, most notably arising within the intraarticular space and resulting in chronic inflammation and degeneration of affected joints. Endogenous clotting factor activity relative to normal levels determines the severity of HA symptoms, as mild (> 5–40%), moderate (1–5%), or severe (< 1%). Within the current environment of rapid evolution in HA management, we seek to understand the interplay of condition severity and health-related quality of life (HRQoL) to characterise and differentiate unmet needs among people with HA (PwHA). Methods: A generalised linear regression model (GLM) was developed to explore the relationship between HA severity and EQ-5D-5 L index score from adult HA patients sampled in the "Cost of Haemophilia across Europe – a Socioeconomic Survey II" (CHESS II) cross-sectional, retrospective burden of illness study among adults with hereditary haemophilia A or B from eight European countries. HA patients of any severity with no active inhibitors during the 12 months prior to data capture and a completeEQ-5D-5 L response were included. A base GLM model was specified with covariates for demographic and clinical characteristics (age, body mass index, country, employment, HA severity, annual bleeding rate, problem joints, and chronic pain). Results: Of 381 evaluable patients, 221 (58.0%) had severe HA, 96 (25.2%) had moderate HA, and 64 (16.8%) had mild HA. Among the covariates included in the GLM model and after controlling for haemophilia-related outcomes, a significant association was observed between mild HA and higher EQ-5D-5 L index score (average marginal effects, 0.084; p = 0.016) relative to severe HA. Patient country of residence and magnitude of HA-related chronic pain were also associated with significant differences in index scores, with the latter showing a negative relationship with HRQoL outcomes. Conclusions: Condition severity and chronic pain are significant predictors of HRQoL in PwHA. Durable bleeding protection and effective management of chronic pain have the potential to address unmet treatment needs in this population. [ABSTRACT FROM AUTHOR]

Introduction: The physical pain and disability affecting many people with haemophilia A (PwHA) are known detractors from psychological wellbeing. While psychosocial support is considered a core tenet of the haemophilia comprehensive care structure, the extent to which mental health challenges are detected and monitored by the individuals treating haematologist remains relatively unexplored. Aim: To describe prevalence of anxiety and depression in a real‐world cohort of adult PwHA and evaluate the congruence in reporting of anxiety or depression (A/D) between PwHA and their treating physicians. Methods: Data for PwHA without inhibitors was drawn from the European 'Cost of Haemophilia: A Socioeconomic Survey II' (CHESS II) study. Haematologist‐indicated comorbidities of anxiety and depression were unified into a single A/D indicator. The EQ‐5D‐5L health status measure was used to characterise self‐reported A/D, with individuals stratified into two non‐mutually exclusive subgroups based on level of A/D reported (Subgroup A: 'some' or above; Subgroup B: 'moderate' or above). Result: Of 381 PwHA with evaluable EQ‐5D‐5L responses, 54% (n = 206) self‐reported at least some A/D (Subgroup A) and 17% (n = 66) reported at least moderate A/D (Subgroup B). Patient‐physician congruence in A/D reporting was 53% and 76% for Subgroups A and B, respectively. Descriptive analysis suggested that individuals with physician‐ and/or self‐reported A/D experienced worse clinical outcomes (bleeding events, joint disease, chronic pain). Conclusion: While adverse clinical outcomes appear to correlate with A/D, self‐reports of moderate–severe symptoms occasionally lacked formal recognition from treating physicians. Cross‐disciplinary surveillance of mental health issues could improve both psychological and clinical outcomes among PwHA. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT). Methods: Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020). Results: We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance. Discussion: The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect. [ABSTRACT FROM AUTHOR]

Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than motor symptoms in cervical dystonia (CD). Some cognitive impairments have been reported; however, findings are inconsistent, and described across mixed groups of dystonia. The current review aimed to examine the evidence for cognitive impairments in CD. MEDLINE, EMBASE, PsychINFO and Web of Science databases were searched. Studies were included if they met the following criteria (i) cross-sectional or longitudinal studies of adults with CD, (ii) where the results of standardised measures of cognitive or neuropsychological function in any form were assessed and reported, (iii) results compared to a control group or normative data, and (iv) were published in English. Results are presented in a narrative synthesis. Twenty studies were included. Subtle difficulties with general intellectual functioning, processing speed, verbal memory, visual memory, visuospatial function, executive function, and social cognition were identified while language, and attention and working memory appear to be relatively spared. Several methodological limitations were identified that should be considered when interpreting the evidence to describe a specific profile of cognitive impairment in CD. Clinical and research implications are discussed. [ABSTRACT FROM AUTHOR]

This study provides a quantitative synthesis of meta-analytic evidence for the effectiveness of very broadly defined positive psychological interventions (PPIs), i.e. interventions that enhance well-being through pathways consistent with positive psychology theory. The definition covers a wide range of PPIs including single and multi-element PPI programs as well as mindfulness, mind-body, and physical exercise-based interventions. Five databases were searched. One hundred and ninety eight meta-analyses involving 4,065 primary studies and 501,335 participants were selected for review. Using the AMSTAR-2 criteria, the selected meta-analyses were found to be of moderate or high quality. At post-intervention, PPIs had a significantly small to medium effect on well-being, QoL, strengths, depression, anxiety, and stress. Gains were partially maintained at 7.5-month follow-up. Mind-body PPIs such as yoga were particularly effective. Individuals who engaged in longer, face-to-face programs benefited most. This mega-analysis shows that PPIs have an extensive evidence base supporting their effectiveness. [ABSTRACT FROM AUTHOR]

Background: The Adolescents and Adults Living with Perinatal HIV (AALPHI) study is one of only three cohort studies worldwide evaluating the impact of HIV on young people living with perinatal HIV (PLHIV) relative to a comparable group of HIV negative young people in close relationship with an HIV positive individual, for example, their mother, sibling or partner. This project aimed to engage young people with the AALPHI study findings, help them take ownership, and decide how they would disseminate the key messages to both study participants and to the wider community. Methods: In brief, 318 PLHIV and 100 HIV negative adolescents participated in AALPHI, where they each were interviewed twice, around two years apart. They were asked a wide range of psychosocial and risk behaviour questions and their cognitive function was assessed. We invited three AALPHI participants and seven members of the Youth Trials Board at the Children's HIV Association (CHIVA) to attend up to four workshops. They were provided with the key AALPHI research findings and asked to develop them into a format that was accessible and understandable for young people. Some who had not participated before formed a group in the fourth dissemination workshop that confirmed the most important concepts and results. Results: The young people decided to develop a film and a leaflet about the AALPHI findings and co-produced them with a film maker and graphic designer. Challenges included working with the film maker and the venue for the first three dissemination workshops was an office space which was not ideal. Conclusion: Engaging young people in the dissemination of the AALPHI findings ensured the results were communicated in a way that was more likely to be relevant, accessible and useful to those affected by the study. This project demonstrates how young people in potentially stigmatised areas of care, such as HIV, can be involved in research dissemination. Plain English summary: Informing young people of the results of a study in which they participated, in a manner they can understand, is an ethical minimum. Increasingly, young people themselves may be involved in this dissemination activity, to ensure that study results are communicated in a way which is more likely to be relevant, accessible and useful to those directly affected by the study. The Adolescents and Adults Living with Perinatal HIV (AALPHI) study is a cohort study evaluating the impact of HIV on young people living with perinatal HIV (PLHIV) relative to HIV negative young people affected by HIV. This project aimed to engage PLHIV with the AALPHI findings, and help them take ownership of their dissemination, deciding how to communicate key messages to study participants and the wider community. We invited three AALPHI participants and seven members of a Youth Trials Board at the Children's HIV Association, (CHIVA), to attend four workshops. We provided them with key AALPHI findings and asked them to develop them into an understandable format for young people. They co-produced the content for a film and a leaflet about the results, working with a film maker and graphic designer. The 4th comprised of three workshop participants and seven new participants from CHIVA. This work shows that young PLHIV can be part of the process of evaluating study results and guiding dissemination by creating outputs that align with young people's priorities. This area of work could be further developed in the future through direct evaluation of participant involvement. [ABSTRACT FROM AUTHOR]

Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's behaviour. There is growing recognition of the clinical, diagnostic, and prognostic value of assessing a person's ability to perform social cognitive tasks, particularly aspects of theory of mind, such as mentalising. One such measure of mentalising is the 'Reading the Mind in the Eyes' test (RMET). This systematic review and meta-analysis consider performance on the RMET, applied to people with neurodegenerative conditions in matched control studies, since its publication in 2001. Overall, this review includes 22 papers with data from N = 800 participants with neurodegenerative conditions: Alzheimer's disease, n = 31; Parkinson's disease, n = 221; Lewy body dementia, n = 33; motor neuron disease, n = 218; Huntington's disease n = 80; multiple sclerosis, n = 217; and N = 601 matched typical controls. Our meta-analyses show that deficits in mentalising, as measured by the RMET, are consistently reported across neurodegenerative conditions, with participants in both early and late disease stages being affected. Social cognition is an emerging field of cognitive neuroscience requiring specific and sensitive measurement across each subdomain. Adult-based meta-normative data feature, for which future groups or individuals could be compared against, and hypotheses relating to the source of these mentalising deficits are further discussed. This review was registered with PROSPERO (CRD42020182874). [ABSTRACT FROM AUTHOR]

Background: Haemophilia A carries a substantial healthcare burden, affecting health-related quality of life (HRQoL). The Cost of Haemophilia in Men: a Socioeconomic Survey II (CHESS II), a retrospective real-world study, characterised the burden of haemophilia and its impact on HRQoL and work productivity. The current analysis explored the impact of bleeding events on HRQoL and work productivity in Europe. This analysis focused on data collected from males aged 18 to 64 years with haemophilia A without inhibitors who were receiving replacement factor products or a monoclonal antibody and were not participating in a clinical trial at the time of study recruitment. Descriptive statistics were analysed using scores from EuroQoL's EQ-5D-5L index and EQ-VAS analogue scale and the Work Productivity and Activity Index Specific Health Problem (WPAI:SHP) percentage scores stratified by the number of annual bleeding events (ABs) 0, 1, 2, 3–4, or ≥ 5. Results: Of 918 males with haemophilia A in CHESS II, 318 met inclusion criteria and had data available for HRQoL measures; mean age (SD) was 33.8 (12.1) years and 96% were White. Mean (SD) ABs of 2.7 (2.9) occurred over the preceding 12 months: 20% had 3 or 4 ABs; 17% had ≥ 5 ABs. Mean EQ-5D-5L index scores for patients with 0, 1, 2, 3–4, or ≥ 5 ABs were 0.92, 0.76, 0.76, 0.71, and 0.56, respectively. Mean (SD) EQ-VAS scores were 86.9 (13.6), with 0 ABs versus 69.5 (19.1) for 3 or 4 ABs and 61.2 (17.2) for ≥ 5 ABs. Mean percentage of overall work productivity loss on the WPAI:SHP questionnaire ranged from 9.70 to 0 ABs to 47.65 for ≥ 5 ABs. Conclusions: In this European sample of adult men with haemophilia A, HRQoL and work productivity scores were lower among those reporting more AB events. Bleeding burden appears to affect HRQoL and productivity; however, this cross-sectional analysis limits the ability to draw firm conclusions on causality. [ABSTRACT FROM AUTHOR]

Introduction: Adequate prophylactic treatment and physical activity improve joint health and clinical outcomes for people with haemophilia A (HA). However, non‐clinical joint‐related burden of moderate (MHA) and severe (SHA) HA has not been well characterised. Aim: To quantify the joint health‐related humanistic and economic burden of MHA and SHA in Europe. Methods: A retrospective analysis of the cross‐sectional CHESS population studies using a patient‐centric measure of joint health (problem joints, PJs: chronic joint pain and/or limited range of movement due to compromised joint integrity with or without persistent bleeding) was conducted. Descriptive statistics summarised health‐related quality of life (HRQoL), work productivity/activity impairment and costs by number of PJs (0, 1 or ≥2) and HA severity. Results: A total of 1171 patients were included from CHESS‐II (n = 468) and CHESS‐PAEDs (n = 703). In both studies, 41 and 59% of patients had MHA and SHA, respectively. Prevalence of ≥2 PJs was similar with MHA and SHA (CHESS‐II: 23 and 26%; CHESS‐PAEDs: 4 and 3%, respectively). HRQoL was worse with an increasing number of PJs (CHESS‐II:.81 vs..66 with 0 and ≥2 PJs, respectively, for MHA;.79 vs..51 for SHA; CHESS‐PAEDs:.64 vs..26 and.72 vs..14). Total costs increased with increasing PJs regardless of severity in CHESS‐II (€2923 vs. €22,536 with 0 and ≥2 PJs, respectively, for MHA; €11,022 vs. €27,098 for SHA) and CHESS‐PAEDs (€6222 vs. €11,043 for MHA; €4457 vs. €14,039 for SHA). Conclusion: Presence of PJs was associated with a substantial humanistic and economic burden on patients with MHA or SHA across the lifespan. [ABSTRACT FROM AUTHOR]

Introduction: The "problem joint" (PJ) concept was developed to address patient‐centric needs for a more holistic assessment of joint morbidity for people with haemophilia (PwH). Aim: To quantify the humanistic burden of PJs in PwH to further support validation of the PJ outcome measure. Methods: Multivariable regression models evaluated the relationship between PJs and health‐related quality of life (HRQoL, EQ‐5D‐5L) and overall work productivity loss (WPL) using data from the 'Cost of HaEmophilia: a Socioeconomic Survey' population studies (adults: CHESS II, CHESS US+; children/adolescents: CHESS‐Paeds). Covariates included were haemophilia severity, age, comorbidities and education. Results: The CHESS II sample included 292 and 134 PwH for HRQoL and WPL analyses, mean age 38.6 years (39% ≥1 PJ, 61% none). CHESS US+ included 345 and 239 PwH for HRQoL and WPL, mean age 35 years (43% ≥1 PJ, 57% none). CHESS‐Paeds included 198 PwH aged 4–17 (HRQoL only), mean age 11.5 years (19% ≥1 PJ, 81% none). In CHESS II and CHESS US+, presence of PJs was associated with worse HRQoL (Both p <.001). Few CHESS‐Paeds participants had PJs, with no significant correlation with HRQoL. In CHESS II, upper body PJs were significantly correlated to WPL (p <.05). In CHESS US+, having ≥1 PJ or upper and lower body PJs were significantly correlated to WPL (vs. none; both p <.05). Conclusion: This study has shown a meaningful burden of PJs on PwH, which should be considered in clinical and health policy assessments of joint health. [ABSTRACT FROM AUTHOR]

Introduction: Gene therapy clinical trials measure steady‐state clotting factor expression levels (FELs) to evaluate the modulation of the bleeding phenotype, aiming to offer consistent protection against breakthrough bleeding events. The link between FELs and bleeding risk in people with haemophilia B (PwHB) is not well understood. Aim: We evaluated the association between FEL and ABR in PwHB. Methods: This cross‐sectional study extended the CHESS burden of illness studies in Europe and the United States. Recruitment of additional adult males with haemophilia B supplemented the existing CHESS sample size of PwHB and FELs. PwHB receiving prophylaxis were excluded, as fluctuating FELs may have confounded the analysis. Demographic and clinical characteristics were reported descriptively. Any recorded baseline FEL was reported by the haemophilia‐treating physicians according to the medical records. Generalised linear models with log link explored the association between changes in FEL and ABR. Results: The study included 407 PwHB and no inhibitors receiving on‐demand treatment. Mean age was 36.7 years; 56% from the EU, 44% from the United States. Mean baseline FEL was 9.95 IU/dl (SD, 10.47); mean ABR was 2.4 bleeds/year (SD, 2.64). After adjusting for covariates, the model showed that for every 1% increase in FEL the average ABR decreased by.08 (p <.001). Predicted number of bleeding events according to FEL showed a significant non‐linear relationship between FEL and ABR (p <.05). Conclusion: This analysis showed a significant relationship between FEL and ABR, where increases in FEL were associated with decreases in ABR among men with HB in Europe and the US. [ABSTRACT FROM AUTHOR]

I This essay is part of a series of essays that are based on interviews conducted for this special issue with people who practice risk communication related to human or natural hazards as part of their professions i . EPA Administrator Gina McCarthy and Tom Burke went to Flint to announce emergency actions and meet with Flint's Mayor who wanted to "rip out the lead pipes." Tom Burke - Listen to the community FLINT, MICHIGAN - POLLUTED DRINKING WATER As leader of the Office of Research and Development and Agency Science Advisor, Burke was the top Environmental Protection Agency (EPA) scientist during Flint Michigan's 2016 contaminated water crisis. [Extracted from the article]

Objective: Borderline personality disorder (BPD) is a psychiatric condition characterised by a pervasive pattern of impulsivity, low self-image, and interpersonal conflicts. Previous findings indicate a mixed relationship between BPD and social cognition; little research as investigated whether BPD traits influence performance on specific elements of social cognitive tasks, i.e., positive/negative valence. Method: Community-based typical controls (n = 151; 51% female) were recruited through an online survey. Participants completed aspects of the Personality Assessment Inventory pertaining to BPD traits, the Interpersonal Reactivity Index, and measures of both emotion recognition and mentalising. Results: Following group stratification into high/low BPD traits, participants with high BPD traits were observed to perform significantly better when identifying negative valence stimuli. Furthermore, high levels of affect instability was found to significantly influence negative valence recognition. Conclusion: This research highlights previous research which shows a paradox between higher performance on measures of social cognition, with a group of individuals who report significant interpersonal and relational difficulties. This research supports the assessment of social cognitive processes for people with BPD and/or high BPD traits to support clinical formulation of strengths and difficulties. [ABSTRACT FROM AUTHOR]

Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p <.00013) with moderate to large effect sizes (.11–.76) throughout all significant subsegments. In this prospective community‐based cohort of school‐age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non‐clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along‐tract analysis of white matter tracts. [ABSTRACT FROM AUTHOR]

Background: Using a pharmacokinetic (PK)-guided approach to personalize the dose and frequency of prophylactic treatment can help achieve and maintain targeted factor VIII (FVIII) trough levels in patients with hemophilia A. Objective: Investigate clinical and healthcare resource use outcomes in patients with hemophilia A treated with or without PK-guided prophylaxis using data from the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) II database. Methods: CHESS II was a cross-sectional, retrospective, burden-of-illness study incorporating data from eight European countries. Patients were eligible for this analysis if they were male, ≥ 18 years of age, and diagnosed with congenital hemophilia A of any severity. The clinical endpoints included annualized bleeding rate (ABR), presence and number of problem/target joints, and occurrence of joint surgeries. Healthcare resource utilization endpoints included the number of hematologist consultations and bleed-related hospitalizations or emergency department admissions. Data from November 2018 to October 2020 were included and were stratified according to treatment regimen and use of PK-guided dosing. Results: Altogether, 281 patients on prophylaxis had available FVIII trough level data. Mean (SD) age was 35.7 (13.8) years. A specific FVIII trough level was targeted in 120 (42.7%) patients and 47 (39.2%) received PK-guided dosing. Patients receiving PK-guided dosing had a mean (SD) ABR of 2.8 (2.1) and target joint number of 0.5 (0.7), compared with 3.9 (2.7) and 0.9 (1.4), respectively, for patients receiving non–PK-guided treatment. The mean (SD) number of hematologist consultations was 7.1 (5.3) for patients receiving PK-guided dosing versus 10.7 (5.7) for those who were not. A higher proportion of patients in the non–PK-guided group required hospitalization during their lifetime compared with the PK-guided group. Conclusion: This analysis of real-world data suggests that PK-guided dosing for prophylaxis has a beneficial impact on clinical and healthcare resource utilization outcomes in patients with hemophilia A. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia is a complex functionally debilitating neurodevelopmental disorder, with associated social cognitive impairment. Corpus Callosum (CC) white matter tracts deficits are reported for people with schizophrenia; however, few studies focus on interhemispheric processing relative to social cognition tasks. This study aimed to determine if a relationship between the CC and social cognition exists. Method: In this cross-section study, a sample of n = 178 typical controls and n = 58 people with schizophrenia completed measures of mentalising (Reading the Mind in the Eyes), emotion recognition outcome and reaction time (Emotion Recognition Test), and clinical symptoms (Positive and Negative Symptom Scale), alongside diffusion-based tract imaging. The CC and its subregions, i.e., the genu, body, and splenium were the regions of interest (ROI). Results: Reduced white matter tract integrity was observed in the CC for patients when compared to controls. Patients performed slower, and less accurately on emotion recognition tasks, which significantly and negatively correlated to the structural integrity of the CC genu. Tract integrity further significantly and negatively related to clinical symptomatology. Conclusions: People with schizophrenia have altered white matter integrity in the genu of the CC, compared to controls, which relates to cognitive deficits associated with recognising emotional stimuli accurately and quickly, and severity of clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Staff member's views and attitudes can have a significant impact on people with an intellectual disability. This study explores staff attitudes and experiences of people with an intellectual disability's expression of relationships and sexuality across service providers in Ireland. Methods: Staff (n = 86) from service providers (n = 5) completed the Attitudes to Sexuality Questionnaire‐Individuals with an Intellectual Disability (ASQ‐ID) and open‐ended questions. Results: Multidirectional significant differences were noted on staff attitudes to sexuality based on demographic factors, that is, age, education, as well as non‐demographics, for example, attendance at training, and active practising of religion. Qualitatively, three themes emerged: "Unsupported and Frustration"; "Taboo Subject Matter" and "Vulnerability and Access to Education". Staff reported a lack of service supports, dominant conservative cultures and people with an intellectual disability's vulnerability. Conclusion: This study highlights the need for improved service practices and enhanced provisions for staff and the people with an intellectual disability that they support. [ABSTRACT FROM AUTHOR]

Background: Haemophilia bears substantial humanistic and economic burden on children and their caregivers. Characterising the differential impact of severe versus moderate paediatric haemophilia is important for clinical and health policy decisions. We analysed health-related quality of life (HRQoL), annual direct medical (excluding factor treatment costs), non-medical and societal costs among children and adolescents with moderate and severe haemophilia A or B without inhibitors from the European CHESS-PAEDs study. Information was reported by physicians and caregivers; patients aged ≥ 8 years self-reported their HRQoL. Descriptive statistics summarised demographic and clinical characteristics, costs, and HRQoL scores (EQ-5D-Y). Regression models estimated differences in HRQoL and costs for moderate versus severe haemophilia adjusting for age, body mass index z-score, country, number of comorbidities, and weight-adjusted annual clotting factor consumption.Results: The analytic sample comprised 794 patients with a mean age of 10.5 years; most had haemophilia A (79%) and 58% had severe haemophilia. Mean predicted direct medical costs in moderate patients were two-thirds of the predicted costs for severe disease (€3065 vs. €2047; p < 0.001; N = 794), while societal costs were more than half of the predicted costs for children with severe haemophilia (€6950 vs. €3666; p < 0.001; N = 220). Mean predicted HRQoL scores were 0.74 and 0.69 for moderate and severe disease, respectively (p < 0.05; N = 185).Conclusion: Children with haemophilia and their caregivers displayed a significant economic and humanistic burden. While severe patients showed the highest direct medical and societal costs, and worse HRQoL, the burden of moderate haemophilia on its own was substantial and far from negligible. [ABSTRACT FROM AUTHOR]

Background: The lifelong nature of haemophilia makes patient-centred and societal assessments of its impact important to clinical and policy decisions. Quantifying the humanistic and economic burden by severity is key to assessing the impact on healthcare systems. We analysed the annual direct medical (excluding factor replacement therapy costs) and non-medical costs as well as societal costs and health-related quality of life (HRQoL) of mild, moderate and severe disease among adults with haemophilia A or B without inhibitors in Europe. Participants in the CHESS II study reported their HRQoL, non-medical costs, and work impairment; physicians provided costs and consultation history from the medical chart. Descriptive statistics summarized patient characteristics, costs, and HRQoL scores. Regression models estimated differences in outcomes for moderate and severe versus mild disease, adjusting for age, body mass index, country, comorbidities, weight-adjusted factor consumption and education.Results: The analytic sample included 707 patients with a mean age of 38 years; the majority of patients had haemophilia A (81%), and 47% had severe disease, followed by moderate (37%) and mild disease (16%). Patients with severe or moderate disease had on average higher direct costs, €3105 and €2469 respectively, versus mild disease. Societal costs were higher for patients with severe and moderate disease by €11,115 and €2825, respectively (all P < 0.01). HRQoL scores were also significantly worse for severe and moderate patients versus those with mild disease.Conclusion: Severity of haemophilia is predictive of increasing economic and humanistic burden. The burden of moderate disease, as measured by direct costs and HRQoL, did not appear to be substantially different than that observed among patients with severe haemophilia. [ABSTRACT FROM AUTHOR]

Following the global outbreak of COVID-19 in March 2020, individuals report psychological distress associated with the "new normal"—social distancing, financial hardships, and increased responsibilities while working from home. Given the interpersonal nature of stress and coping responses between romantic partners, based on the systemic transactional model this study posits that perceived partner dyadic coping may be an important moderator between experiences of COVID-19 psychological distress and relationship quality. To examine these associations, self-report data from 14,020 people across 27 countries were collected during the early phases of the COVID-19 pandemic (March–July, 2020). It was hypothesized that higher symptoms of psychological distress would be reported post-COVID-19 compared to pre-COVID-19 restrictions (Hypothesis 1), reports of post-COVID-19 psychological distress would be negatively associated with relationship quality (Hypothesis 2), and perceived partner DC would moderate these associations (Hypothesis 3). While hypotheses were generally supported, results also showed interesting between-country variability. Limitations and future directions are presented. [ABSTRACT FROM AUTHOR]

Gene therapy trials aim to provide a functional cure for patients with haemophilia B (HB), and treatment impact is analyzed by factor IX expression levels (FELs). We investigated the relationship of FELs with health-related quality of life (HRQoL) and costs. This was a retrospective cross-sectional analysis of the European (CHESS I-II) and US (CHESS-US) CHESS population studies. Physicians recruited consecutive patients and extracted information from the medical records; patients completed questionnaires between 2014 and 2015 (CHESS-I), 2018–2019 (CHESS-II) and 2019 (CHESS US). Patients with inhibitors were excluded. HRQoL was assessed using the EQ-5D-5L. Twelve-month haemophilia-related direct medical costs included office visits and hospitalizations based on country-level unit costs. A Tobit model was used to analyze FELs and HRQoL and generalized linear models for direct medical costs. A total of 191 men with HB completed the EQ-5D questionnaire; the mean age was 36.8 years, with a mean FEL of 10.1 IU/dL (median, 4.0). Mean EQ-5D was 0.77 (SD, 0.23). The Tobit model adjusting for age, body mass index and blood-borne viruses showed every 1% increase in FEL was associated with +0.006 points in the mean EQ-5D score (p =.003). Mean haemophilia-related direct medical costs excluding factor replacement therapy were €2,028/year (median, €919) in CHESS I-II (EU, n = 226), and $7,171/year (median, $586) in CHESS US (n = 181). Adjusted EU and US models showed every 1% increase in FEL was associated with a decrease in haemophilia-related direct medical costs of €108/year and $529/year, respectively. Direct medical costs were based on physician extraction of encounters from medical records, potentially underestimating costs of care. The voluntary nature of participation may have introduced selection biases. We observed a significant association of increases in FEL with increased HRQoL and decreased costs in Europe and the United States among men with HB and no inhibitors. [ABSTRACT FROM AUTHOR]

Background: Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019-2020). All outcomes were summarised using descriptive statistics.Results: A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67.Conclusions: These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society. [ABSTRACT FROM AUTHOR]

Background: This longitudinal cohort study aimed to examine the impact of the first wave of the COVID‐19 pandemic in Ireland on parents of children with externalising difficulties, in comparison to parents of children without such difficulties. Method: Parents of 159 children completed online self‐report measures at three time points during the first wave of the COVID‐19 pandemic; (a) Delay and Mitigation Phase (March 2020 to May 2020), (b) Reopening of Society Phase (June 2020 to July 2020) and (c) Wave 2 Case Acceleration Phase (September 2020 to October 2020). Participants were allocated to the clinical group if they met the clinical cut off point on the Conduct or Hyperactivity/Inattention subscales of the Strengths and Difficulties Questionnaire at Time 1. Results: Parents of children with externalising difficulties experienced significantly higher levels of stress, lower levels of wellbeing and engaged in higher levels of avoidant‐focused coping strategies longitudinally. There was a significant difference between outcomes at the different phases of the COVID‐19 pandemic, for stress related to parenting, personal/family stress related to the impact of the COVID‐19 and type of coping strategies employed. Children with externalising difficulties, in comparison to children without externalising difficulties, showed significantly greater adjustment over time for behavioural and emotional difficulties, as reported by their parents. Conclusions: Results provide important information regarding the trajectory of psychological outcomes in parents of children with externalising difficulties over the first wave of the COVID‐19 pandemic, highlighting the need for increased parental supports during, and after, the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Few studies have examined the real‐world impact of haemophilia on daily activities and work productivity in people with severe haemophilia A (PWSHA). Aim: To determine clinical attributes and treatment characteristics associated with impairment in daily activities and work among PWSHA using the patient‐reported Work Productivity and Activity Impairment‐General Health Questionnaire (WPAI‐GH). Methods: PWSHA were asked to complete the WPAI‐GH as part of the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) study. Outcomes were determined for activity impairment (AI), absenteeism, presenteeism and overall work productivity loss (WPL). Descriptive statistics and regression analyses were used to evaluate the association between these outcomes and clinical and treatment attributes. Results: Overall, 376 participants completed the AI element of WPAI‐GH; 175 were employed and thus also reported on work impact. Mean ± standard deviation scores were as follows: AI = 34.2% ± 25.8%; absenteeism = 0.06% ±0.2%; presenteeism = 26.8% ± 22.4%; WPL = 28.6% ± 24.0%. Increased AI and WPL were associated with high haemophilia‐related morbidity, measured both as chronic pain (p <.001 for both) and joint synovitis (AI: p <0.001; WPL: p =.017). In descriptive and multivariate analyses, lifelong prophylaxis was associated with reduced AI (p <.001 and p =.031, respectively); high therapy adherence was associated with reduced AI (p =.001 and p =.012, respectively) and with reduced WPL (p <.001 and p =.012, respectively). Conclusion: The WPAI‐GH identified haemophilia‐related morbidity and treatment characteristics, including therapy regimen and adherence, as key attributes impacting functional impairment and work contributions of PWSHA. Early prophylactic intervention and greater adherence to therapy may lead to lower AI and WPL in PWSHA. [ABSTRACT FROM AUTHOR]

Aims: Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. Materials and methods: With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including "bleed into joint", "bleed not into joint", "no bleed" and "death". Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. Results: Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. Conclusions: This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is often associated with cognitive and/or behavioural impairment. Cognitive reserve (CR) may play a protective role in offsetting cognitive impairment. This study examined the relationship between CR and longitudinal change in cognition in an Irish ALS cohort.Methods: Longitudinal neuropsychological assessment was carried out on 189 patients over 16 months using the Edinburgh cognitive and behavioural ALS screen (ECAS) and an additional battery of neuropsychological tests. CR was measured by combining education, occupation and physical activity data. Joint longitudinal and time-to-event models were fitted to investigate the associations between CR, performance at baseline and decline over time while controlling for non-random drop-out.Results: CR was a significant predictor of baseline neuropsychological performance, with high CR patients performing better than those with medium or low CR. Better cognitive performance in high CR individuals was maintained longitudinally for ECAS, social cognition, executive functioning and confrontational naming. Patients displayed little cognitive decline over the course of the study, despite controlling for non-random drop-out.Conclusions: These findings suggest that CR plays a role in the presentation of cognitive impairment at diagnosis but is not protective against cognitive decline. However, further research is needed to examine the interaction between CR and other objective correlates of cognitive impairment in ALS. [ABSTRACT FROM AUTHOR]

Social cognition is the ability to identify, understand, and interpret mental states and emotions. Psychopathic traits are typically described in two ways; Primary: shallow affect, emotional detachment, and relationship difficulties, and Secondary Psychopathic Traits: antisocial traits, impulsiveness, and emotional dysregulation. People with high psychopathic traits tend to perform lower on measures of social cognition. This study investigated the relationship of social cognition (mentalising) to primary and secondary psychopathic traits in a non-clinical sample, and investigated the psychometric properties of the Reading the Mind in the Eyes Test (RMET) Short Forms (A and B). A community-based male sample (N = 1,000; age range 18–78) was recruited through an online platform. Psychopathic traits were measured using Levenson, Kiehl, and Fitzpatrick's Self-Report Psychopathy Scale, and stratified into Primary and Secondary Psychopathic traits. Secondary validation of the RMET Short Forms was completed investigating scale reliability, and validity. Findings suggest excellent psychometrics in a large community cohort for the RMET Short Forms (A and B), with significant negative correlations on social cognitive performance and high self-report psychopathy. The item valence within the social cognitive measure (positive, negative, and neutral affect stimuli) was also examined, and correlated significantly with both Primary and Secondary Psychopathic traits. This study provides further validation of the RMET Short Forms (A and B), and adds to the literature on the scale by investigating performance on short-form specific valence. This study further suggests that in a non-clinical community sample of males, that higher psychopathic traits correlated significantly, and negatively, with social cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients' functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The 'Cost of Severe Hemophilia across the US: a Socioeconomic Survey' (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US.Results: We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931.Conclusions: This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies. [ABSTRACT FROM AUTHOR]

Background: Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages. While RCT and pharmacokinetic data support the value of Kovaltry [an unmodified full-length recombinant factor VIII (FVIII) product], real world evidence in children is lacking. This report describes a descriptive and multivariate analysis of the effectiveness of Kovaltry in children with hemophilia A in the real-world setting, using data from medical chart abstraction and cross-sectional surveys of physicians, patients, and caregivers.Results: Male patients aged < 18 years with moderate or severe hemophilia A, residing in five European countries and treated with FVIII were studied. The co-primary endpoints were the annualized bleeding rate (ABR) and the annual FVIII utilization rate. Twenty nine patients treated with Kovaltry were included, of whom 93% had severe disease and 75% were on continuous prophylactic treatment. The mean ABR was 2.66 ± 2.06, with rates decreasing with age. The children received on average 2.45 infusions per week, consistent across age groups (median 3; range 1-3). There were no reports of inhibitor development or adverse events in the study (AEs), and all patients were satisfied or very satisfied with the treatment. An exploratory multivariate analysis suggests no significant difference in ABR or units utilized between Kovaltry and some extended half life products in children with severe hemophilia A, though characteristics of these patient cohorts were markedly different.Conclusion: This analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A. [ABSTRACT FROM AUTHOR]

Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2–3 or 7–14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including "bleed into joint", "bleed not into joint", "no bleed" and "death". Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment accounts for >90% of the total HB treatment costs. This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm. [ABSTRACT FROM AUTHOR]

Objective: Deficits in social cognition are part of the cognitive phenotype of amyotrophic lateral sclerosis (ALS). This study investigated the psychometric properties and test-retest reliability of two short-form versions of the Reading the Mind in the Eyes Test. Method: Patients with ALS (n = 50), alongside age and IQ matched controls (n = 50) were recruited. The Reading the Mind in the Eyes Test (RMET) was apportioned according to previously published psychometric properties yielding two short forms. The internal consistency, test–retest reliability, item difficulty, and discrimination coefficient were computed to determine the utility of the short forms. Two one-sided t-test (TOST) assessed equivalency, and a ROC curve analysis determined a cutoff for impairment. Results: Cronbach's Alpha > 0.7 was observed for the RMET Short Form A and RMET Short Form B, indicating adequate internal consistency. Both RMET Short Forms had excellent psychometric properties when discriminating between ALS patients who performed well, compared to those who did not, with an overall medium difficulty coefficient observed. The TOST found the short forms to be equivalent. Conclusion: Social cognition is an important cognitive construct in ALS, as is its measurement. This study contributes not only to the psychometric knowledge of this measure, but also to the usability, efficacy, reliability, and repeatability of two short forms. [ABSTRACT FROM AUTHOR]

Objective RA is a progressive, chronic autoimmune disease. We summarize the impact of disease activity as measured by the DAS in 28 joints (DAS28-CRP scores) and pain on productivity and ability to work using the Work Productivity and Activity Impairment questionnaire (WPAI) scores, in addition to the impact of disease duration on the ability to work. Methods Data were drawn from the Burden of RA across Europe: a Socioeconomic Survey (BRASS), a European cross-sectional study in RA. Analyses explored associations between DAS28-CRP score and disease duration with stopping work because of RA, and regression analyses assessed impacts of pain and DAS28-CRP on early retirement and WPAI. Results Four hundred and seventy-six RA specialist clinicians provided information on 4079 adults with RA, of whom 2087 completed the patient survey. Severe disease activity was associated with higher rates of stopping work or early retirement attributable to RA (21%) vs moderate/mild disease (7%) or remission (8%). Work impairment was higher in severe (67%) or moderate RA (45%) compared with low disease activity [LDA (37%)] or remission (28%). Moreover, patients with severe (60%) or moderate pain (48%) experienced increased work impairment [mild (34%) or no pain (19%)]. Moderate to severe pain is significant in patients with LDA (35%) or remission (22%). A statistically significant association was found between severity, duration and pain vs work impairment, and between disease duration vs early retirement. Conclusion Results demonstrate the high burden of RA. Furthermore, subjective domains, such as pain, could be as important as objective measures of RA activity in affecting the ability to work. [ABSTRACT FROM AUTHOR]

Introduction: The benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown. Aim: To elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity ('level') required to avoid a bleeding episode during participation in different types of PA for PWH. Methods: Based on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion. Results: Minimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%‐52% and 12%‐64%, respectively. Conclusion: To support a patient‐centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the effectiveness of the Extension for Community Healthcare Outcomes (Project ECHO) in educating primary care clinicians (PCCs) to provide best practice rheumatic care to patients in under-resourced communities in New Mexico.Methods: Attendee data for weekly teleECHO sessions, lectures, grand rounds, and mini-residency trainings were evaluated from June 2006 to June 2014. Participant feedback was evaluated from January 2009 to December 2014, when the program was approved for continuing medical education (CME) credits. Retrospective review of diagnoses associated with case presentations was conducted from June 2006 to June 2014 to evaluate the types of cases presented. A focus group was conducted with a convenience sample of 8 New Mexico PCCs who participated in ECHO Rheumatology (ECHO Rheum) for 1 year or longer.Results: Over the course of 9 years, ECHO Rheum educated 2,230 clinicians, consisting primarily of physicians (53%) and nurse practitioners (22%). A total of 1,958 CME credits were awarded to those who participated. There were 1,173 cases presented; 85% of the cases reflected the 3 most common diagnoses: rheumatoid arthritis (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). In addition, ECHO Rheum conducted 15 two-day mini-residencies involving 30 PCCs; 21 of these clinicians subsequently completed the American College of Rheumatology online certification.Conclusion: Results from this study demonstrate that participation in ECHO Rheum provides clinicians in under-resourced areas access to best-practice knowledge and training in rheumatology. [ABSTRACT FROM AUTHOR]

Clinical outcomes, including performance on cognitive assessment, in patients with angiographically negative subarachnoid haemorrhage (anSAH) are often interpreted as benign with a good prognostic trajectory. However, diffuse cognitive deficits have been reported within this patient cohort resulting from anSAH, albeit to a lesser extent when compared to other neurovascular events. We consider cognitive outcomes in relation to anSAH to systematically review reported deficits, with a view to quantify and categorise cognitive impairment in this cohort. Anxiety and depression were also included within this review, provided they were assessed alongside cognitive function. Performance deficits in attention and executive function are commonly reported, with set-shifting and interference tasks most commonly impaired in patients. Non-executive cognitive functions are negatively implicated also. Clinical implications and hypotheses relating to the source of these deficits are discussed. This review was formally registered with PROSPERO (CRD42017075294). [ABSTRACT FROM AUTHOR]

Objective: Caregiver burden is a recognised consequence of caring for a patient with neurodegeneration. Amyotrophic lateral sclerosis (ALS) differs from other neurodegenerations by its rapid progression and impairment of motor, cognitive, and behavioural function, which contribute to caregiver burden. However, longitudinal factors that determine the extent of caregiver burden, and in particular the impact of psychological distress among caregivers, have not been fully established.Methods: Patients with ALS (n = 85) and their primary caregivers (n = 85) completed three serial evaluations. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). The Edinburgh Cognitive-Behavioural ALS Screen (ECAS) was used to determine cognitive function in patients. The ALS Functional Rating Scale (ALSFRS-R) measured disease progression.Results: Using the ZBI, caregivers were categorised as high or low burden. In the low burden group, anxiety scores from the HADS predicted caregiver burden (r = 0.410, F = 3.73, p = 0.033), whereas the depression sub-score from the HADS was predictive of caregiver burden in the high burden group (r = 0.501, F = 5.87, p = 0.006) for cross-sectional analyses. Longitudinally, an elevated score on the HADS at Time 1 was the largest predictor of caregiver burden across serial assessments.Conclusion: In a patient cohort with relatively preserved cognitive function (65%), anxiety and depression at Time 1, as measured by the HADS, were the best predictors of caregiver burden at Time 3. This observation provides a mechanism by which caregiver burden can be identified by health-care professionals and a stepped care programme of intervention initiated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of mismatch negativity (MMN), a neurophysiologic marker of non-motor cognitive processing, in amyotrophic lateral sclerosis (ALS). Methods: 89 patients, stratified into 4 different phenotypic presentations of ALS (67 spinal-onset, 15 bulbar-onset, 7 ALS-FTD, 7 C9ORF72 gene careers), and 19 matched controls underwent 128-channel EEG data recording. Subjects were presented with standard auditory tones interleaved with pitch-deviant tones in three recording blocks. The MMN response was quantified by peak amplitude, peak delay, average amplitude, and average delay, 100-300 ms after stimuli. 64 patients underwent cognitive screening using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and 38 participants underwent contemporaneous cognitive assessment using the Stroop Color-Word Interference test (CWIT), which measures attention shift, inhibitory control, and error monitoring. results: The MMN response was observed in frontal and frontocentral regions of patient and control groups. Compared to controls, waveforms were attenuated in early onset, and the average delay was significantly increased in all of the ALS subgroups, with no significant difference between subgroups. Comparing with the control response, the ALS MMN response clustered into four new subgroups characterized by differences in response latency. The increased average delay correlated with changes in the Stroop CWIT; however, it did not show a direct relationship with age, gender, traditional phenotypes, revised ALS Functional Rating Scale, or ECAS scores. conclusion and significance: The MMN response in ALS patients reflects the cognitive dysfunction in specific sub-domains, as the new patient subgroups, identified by cluster analysis, do not segregate with existing clinical or cognitive classifications. Event-related potentials can provide additional quantitative neurophysiologic measures of impairment in specific cognitive sub-domains from which it may be possible to generate novel biologically relevant subgroups of ALS. [ABSTRACT FROM AUTHOR]

The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS-specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Sixty ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity, and overall accuracy of the BBI when compared to the ALS-FTD-Q, were obtained. The mean score of the whole sample on the BBI was 11.45 ± 13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6 ± 14.64, 9.62 ± 11.38; p < 0.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed ( r = 0.807, p < 0.0001), and no significant correlations between the BBI and other clinical/demographic characteristics indicate good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity, and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition. [ABSTRACT FROM AUTHOR]

Background: Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the 'Cost of Haemophilia in Europe: a Socioeconomic Survey' (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level.Results: Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss.Conclusions: The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a 'snapshot' of information for patients with rare diseases. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to illustrate the variation of non-executive cognitive processes, i.e. visual memory, considering executive dysfunction in amyotrophic lateral sclerosis (ALS). Methods: Patients with ALS (n = 203), and matched healthy controls (n = 117) completed a battery of neuropsychological tests. Sub-stratification was based on whether cognitive assessment detected no cognitive abnormalities (NCA: n = 117), multiple executive cognitive deficits (ALS-Exec; n = 56), or a comorbid frontotemporal dementia process (ALS-FTD; n = 30). The Rey-Osterrieth Complex Figure Test (ROCFT) was the main dependent variable for visual memory in this study. Results: Patients and controls significantly differed on the Copy trial (p < 0.0001: ω2 = 0.317) immediate recall (p < 0.0001: ω2 = 0.272) and delayed recall (p < 0.0001: ω2 = 0.308) of the ROCFT. Sub-stratification based on executive dysfunction revealed an association with greater executive dysfunction and lower ROCFT performance. Regression analysis predicted that premorbid IQ, executive function, and demographics predict performance on the ROCFT delayed recall trial (R2 = 0.833). Conclusions: These findings illustrate that patients without executive dysfunction do not show visual memory impairments within this cohort; that patients with executive dysfunction have poorer performance on visual memory tasks; and that the severity of executive dysfunction, as per cognitive categorisation, is related to increased visual memory impairment as tested with the ROCFT. [ABSTRACT FROM AUTHOR]