The Risk of Venous Thromboembolism (VTE) in Men with Benign Prostatic Hyperplasia Treated with 5-Alpha Reductase Inhibitors (5ARIs)

Background: Many men receive 5-alpha reductase inhibitors (5ARIs) for ongoing treatment of benign prostatic hyperplasia (BPH). The increased risk of cardiovascular complications with 5ARIs has been documented in BPH studies and the occurrence of cerebral venous thrombosis, presumably due to increased estrogen level following 5ARI use, was described in multiple case reports. The objective of this study was to determine if 5ARIs with or without alpha blockers (AB) were associated with an increased risk of venous thromboembolism (VTE) in males with BPH. Methods: We conducted a nested case-control study among a population of men ages 40-79 who received at least one 5ARI or AB prescription for treatment of BPH between 1995 and 2015 in the UK-based Clinical Practice Research Datalink GOLD. Cases of incident VTE (pulmonary embolism [PE] or deep venous thrombosis [DVT]) and matched controls were identified from this population. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE in users of 5ARIs compared to users of ABs. Results: For 5ARI only users, the adjusted odds ratios (aORs), (95% CI) for VTE were 1.51 (0.98-2.32) in current 5ARI users and 1.23 (0.70-2.17) in recent/distant past, compared to AB only users. However, the aOR (95% CI) in men who had 50 or more current 5ARI prescriptions compared to users of ABs only was higher: 2.29 (1.14-4.63). For 5ARI with AB use, the aORs, (95% CI) for VTE were 1.16 (0.64-2.10) in current 5ARI+AB users and 1.93 (0.71-5.25) in recent/distant past, compared to AB only users. The aOR (95% CI) in men who had 50 or more current 5ARI+AB prescriptions compared to users of ABs only was 1.65 (0.64-4.26). Conclusion: Current use of 5ARI, particularly long-term use, is associated with an increased risk of incident idiopathic VTE compared to patients treated with AB use only

Estimation of Health State Utility Values in Fabry Disease Using Vignette Development and Valuation

**Background:** Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients’ health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. **Objectives:** The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. **Methods:** Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. **Results:** Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees' responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD $$CEFD$$, severe CEFD, end-stage renal disease $$ESRD$$, stroke, and cardiovascular disease $$CVD$$) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). **Discussion:** Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. **Conclusions:** Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD

Differential activity in Heschl's gyrus between deaf and hearing individuals is due to auditory deprivation rather than language modality

Sensory cortices undergo crossmodal reorganisation as a consequence of sensory deprivation. Congenital deafness in humans represents a particular case with respect to other types of sensory deprivation, because cortical reorganisation is not only a consequence of auditory deprivation, but also of language-driven mechanisms. Visual crossmodal plasticity has been found in secondary auditory cortices of deaf individuals, but it is still unclear if reorganisation also takes place in primary auditory areas, and how this relates to language modality and auditory deprivation.  Here, we dissociated the effects of language modality and auditory deprivation on crossmodal plasticity in Heschl's gyrus as a whole, and in cytoarchitectonic region Te1.0 (likely to contain the core auditory cortex). Using fMRI, we measured the BOLD response to viewing sign language in congenitally or early deaf individuals with and without sign language knowledge, and in hearing controls.  Results show that differences between hearing and deaf individuals are due to a reduction in activation caused by visual stimulation in the hearing group, which is more significant in Te1.0 than in Heschl's gyrus as a whole. Furthermore, differences between deaf and hearing groups are due to auditory deprivation, and there is no evidence that the modality of language used by deaf individuals contributes to crossmodal plasticity in Heschl's gyrus

Immersive bilingualism reshapes the core of the brain

Bilingualism has been shown to affect the structure of the brain, including cortical regions related to language. Less is known about subcortical structures, such as the basal ganglia, which underlie speech monitoring and language selection, processes that are crucial for bilinguals, as well as other linguistic functions, such as grammatical and phonological acquisition and processing. Simultaneous bilinguals have demonstrated significant reshaping of the basal ganglia and the thalamus compared to monolinguals. However, it is not clear whether these effects are due to learning of the second language (L2) at a very young age or simply due to continuous usage of two languages. Here, we show that bilingualism-induced subcortical effects are directly related to the amount of continuous L2 usage, or L2 immersion. We found significant subcortical reshaping in non-simultaneous (or sequential) bilinguals with extensive immersion in a bilingual environment, closely mirroring the recent findings in simultaneous bilinguals. Importantly, some of these effects were positively correlated to the amount of L2 immersion. Conversely, sequential bilinguals with comparable proficiency and age of acquisition (AoA) but limited immersion did not show similar effects. Our results provide structural evidence to suggestions that L2 acquisition continuously occurs in an immersive environment, and is expressed as dynamic reshaping of the core of the brain. These findings propose that second language learning in the brain is a dynamic procedure which depends on active and continuous L2 usage

New insights into the role of motion and form vision in neurodevelopmental disorders

A selective deficit in processing the global (overall) motion, but not form, of spatially extensive objects in the visual scene is frequently associated with several neurodevelopmental disorders, including preterm birth. Existing theories that proposed to explain the origin of this visual impairment are, however, challenged by recent research. In this review, we explore alternative hypotheses for why deficits in the processing of global motion, relative to global form, might arise. We describe recent evidence that has utilised novel tasks of global motion and global form to elucidate the underlying nature of the visual deficit reported in different neurodevelopmental disorders. We also examine the role of IQ and how the sex of an individual can influence performance on these tasks, as these are factors that are associated with performance on global motion tasks, but have not been systematically controlled for in previous studies exploring visual processing in clinical populations. Finally, we suggest that a new theoretical framework is needed for visual processing in neurodevelopmental disorders and present recommendations for future research

Sensory theories of developmental dyslexia: three challenges for research.

Recent years have seen the publication of a range of new theories suggesting that the basis of dyslexia might be sensory dysfunction. In this Opinion article, the evidence for and against several prominent sensory theories of dyslexia is closely scrutinized. Contrary to the causal claims being made, my analysis suggests that many proposed sensory deficits might result from the effects of reduced reading experience on the dyslexic brain. I therefore suggest that longitudinal studies of sensory processing, beginning in infancy, are required to successfully identify the neural basis of developmental dyslexia. Such studies could have a powerful impact on remediation.This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nrn/journal/v16/n1/abs/nrn3836.html

Meta-analytic findings reveal lower means but higher variances in visuo-spatial ability in dyslexia

Conflicting empirical and theoretical accounts suggest that dyslexia is associated with either average, enhanced, or impoverished high level visuo-spatial processing relative to controls. Such heterogeneous results could be due to the presence of wider variability in dyslexic samples, which is unlikely to be identified at the single study level, due to lack of power. To address this, the current study reports a meta-analysis of means and variances in high-level visuo-spatial ability in 909 non-dyslexic and 956 dyslexic individuals. The findings suggest that dyslexia is associated not only with a lower mean performance on visuo-spatial tasks, but also with greater variability in performance. Through novel meta analytic techniques, we demonstrate a negative effect size for mean differences (-.457), but a positive effect size for SD differences (+.118; SD ratio = 1.107). In doing so, this is the first study to demonstrate impoverished visuospatial processing of the majority of individuals with dyslexia in addition to greater variance in performance in this group. The findings advocate for further consideration of both the presence of, and reasons for, increased variance in perception, attention and memory across neurodevelopmental disorders