A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Third Molar Coronectomy vs Total Removal in Second Molar Periodontal Healing.

OBJECTIVES: The objective of this randomised controlled trial was to compare the periodontal healing at the distal of the adjacent second molar after coronectomy or surgical removal and the surgical morbidities of the 2 techniques. METHODS: This is a pilot study of a split-mouth randomised clinical trial comparing the periodontal healing of the adjacent second molar after coronectomy or total removal of lower third molars, which was registered with the University of Hong Kong Clinical Trial Centre as HKUCTR-2948 on 21 February 2020. Cone beam computed tomography (CBCT) scans were taken preoperatively and at 6 months postoperatively. Changes in the bone level from the cemento-enamel junction, periodontal probing depth (PPD), and clinical attachment level (CAL) at the distal of the adjacent second molar were compared. Surgical morbidities in terms of pain, infection, neurologic deficit, root exposure, and need for second surgery for removal were assessed. RESULTS: Forty patients (22 male, 18 female) with mean age of 26.7 years were evaluated at 6 months postoperatively. Both coronectomy and total removal groups demonstrated statistically significant reduction in PPD and CAL. There was an alveolar bone gain of 1.28 ± 0.88 mm in the coronectomy group and 1.13 ± 0.73mm in the control group, which was statistically significant (P < .001 for both groups). CONCLUSIONS: Early findings show the periodontal healing at the adjacent second molar of coronectomy was as good as that of total removal of lower third molar. There were no differences in terms of surgical morbidities between both groups.

Arachidonic acid activates NLRP3 inflammasome in MDSCs via FATP2 to promote post-transplant tumour recurrence in steatotic liver grafts.

Background & Aims: The steatotic grafts have been applied in liver transplantation frequently owing to the high incidence of non-alcoholic fatty liver disease. However, fatty livers are vulnerable to graft injury. Myeloid-derived suppressor cell (MDSC) recruitment during liver graft injury promotes tumour recurrence. Lipid metabolism exerts the immunological influence on MDSCs in tumour progression. Here, we aimed to explore the role and mechanism of inflammasome activation in MDSCs induced by lipid metabolism during fatty liver graft injury and the subsequent effects on tumour recurrence. Methods: MDSC populations and nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome levels were investigated in a clinical cohort and a rat liver transplantation model. The mechanism of NLRP3 activation by specific fatty acids was explored in mouse hepatic ischaemia/reperfusion injury (IRI) with tumour recurrence model and in vitro studies. Results: MDSC populations and NLRP3 levels were increased with higher tumour recurrent rate in patients using steatotic grafts. NLRP3 was upregulated in MDSCs with lipid accumulation post mouse fatty liver IRI. Mechanistically, arachidonic acid was discovered to activate NLRP3 inflammasome in MDSCs through fatty acid transport protein 2 (FATP2), which was identified by screening lipid uptake receptors. The mitochondrial dysfunction with enhanced reactive oxygen species bridged arachidonic acid uptake and NLRP3 activation in MDSCs, which subsequently stimulated CD4+ T cells producing more IL-17 in fatty liver IRI. Blockade of FATP2 inhibited NLRP3 activation in MDSCs, IL-17 production in CD4+ T cells, and the tumour recurrence post fatty liver IRI. Conclusions: During fatty liver graft injury, arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2, which subsequently stimulated CD4+ T cells producing IL-17 to promote tumour recurrence post transplantation. Impact and implications: The high incidence of non-alcoholic fatty liver disease resulted in the frequent application of steatotic donors in liver transplantation. Our data showed that the patients who underwent liver transplantation using fatty grafts experienced higher tumour recurrence. We found that arachidonic acid activated NLRP3 inflammasome in MDSCs through FATP2 during fatty liver graft injury, which led to more IL-17 secretion of CD4+ T cells and promoted tumour recurrence post transplantation. The inflammasome activation by aberrant fatty acid metabolism in MDSCs bridged the acute-phase fatty liver graft injury and liver tumour recurrence.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.

The role of the gut-microbiome-brain axis in metabolic remodeling amongst children with cerebral palsy and epilepsy.

Background: Epilepsy-associated dysbiosis in gut microbiota has been previously described, but the mechanistic roles of the gut microbiome in epileptogenesis among children with cerebral palsy (CP) have yet to be illustrated. Methods: Using shotgun metagenomic sequencing coupled with untargeted metabolomics analysis, this observational study compared the gut microbiome and metabolome of eight children with non-epileptic cerebral palsy (NECP) to those of 13 children with cerebral palsy with epilepsy (CPE). Among children with CPE, 8 had drug-sensitive epilepsy (DSE) and five had drug-resistant epilepsy (DRE). Characteristics at enrollment, medication history, and 7-day dietary intake were compared between groups. Results: At the species level, CPE subjects had significantly lower abundances of Bacteroides fragilis and Dialister invisus but higher abundances of Phascolarctobacterium faecium and Eubacterium limosum. By contrast, DRE subjects had a significantly higher colonization of Veillonella parvula. Regarding microbial functional pathways, CPE subjects had decreased abundances of pathways for serine degradation, quinolinic acid degradation, glutamate degradation I, glycerol degradation, sulfate reduction, and nitrate reduction but increased abundances of pathways related to ethanol production. As for metabolites, CPE subjects had higher concentrations of kynurenic acid, 2-oxindole, dopamine, 2-hydroxyphenyalanine, 3,4-dihydroxyphenylglycol, L-tartaric acid, and D-saccharic acid; DRE subjects had increased concentrations of indole and homovanilic acid. Conclusions: In this study, we found evidence of gut dysbiosis amongst children with cerebral palsy and epilepsy in terms of gut microbiota species, functional pathways, and metabolites. The combined metagenomic and metabolomic analyses have shed insights on the potential roles of B. fragilis and D. invisus in neuroprotection. The combined analyses have also provided evidence for the involvement of GMBA in the epilepsy-related dysbiosis of kynurenine, serotonin, and dopamine pathways and their complex interplay with neuroimmune and neuroendocrinological pathways.

Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA).

Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non­ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM­derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67-4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI - 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Risdiplam in types 2 and 3 spinal muscular atrophy: A randomised, placebo-controlled, dose-finding trial followed by 24 months of treatment.

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an orally administered molecule that modifies SMN2 pre-mRNA splicing to increase functional SMN protein. METHODS: SUNFISH Part 1 was a dose-finding study conducted in 51 individuals with types 2 and 3 SMA aged 2-25 years. A dose-escalation method was used to identify the appropriate dose for the subsequent pivotal Part 2. Individuals were randomized (2:1) to risdiplam or placebo at escalating dose levels for a minimum 12-week, double-blind, placebo-controlled period, followed by treatment for 24 months. The dose selection for Part 2 was based on safety, tolerability, pharmacokinetic, and pharmacodynamic data. Exploratory efficacy was also measured. RESULTS: There was no difference in safety findings for all assessed dose levels. A dose-dependent increase in blood SMN protein was observed; a median twofold increase was obtained within 4 weeks of treatment initiation at the highest dose level. The increase in SMN protein was sustained over 24 months of treatment. Exploratory efficacy showed improvement or stabilization in motor function. The pivotal dose selected for Part 2 was 5 mg for patients with a body weight ≥20 kg or 0.25 mg/kg for patients with a body weight <20 kg. CONCLUSIONS: SUNFISH Part 1 demonstrated a twofold increase in SMN protein after treatment with risdiplam. The observed safety profile supported the initiation of the pivotal Part 2 study. The long-term efficacy and safety of risdiplam are being assessed with ongoing treatment.

Web- and app-based tools for remote hearing assessment: a scoping review.

OBJECTIVE: Remote hearing screening and assessment may improve access to, and uptake of, hearing care. This review, the most comprehensive to date, aimed to (i) identify and assess functionality of remote hearing assessment tools on smartphones and online platforms, (ii) determine if assessed tools were also evaluated in peer-reviewed publications and (iii) report accuracy of existing validation data. DESIGN: Protocol was registered in INPLASY and reported according to PRISMA-Extension for Scoping Reviews. STUDY SAMPLE: In total, 187 remote hearing assessment tools (using tones, speech, self-report or a combination) and 101 validation studies met the inclusion criteria. Quality, functionality, bias and applicability of each app were assessed by at least two authors. RESULTS: Assessed tools showed considerable variability in functionality. Twenty-two (12%) tools were peer-reviewed and 14 had acceptable functionality. The validation results and their quality varied greatly, largely depending on the category of the tool. CONCLUSION: The accuracy and reliability of most tools are unknown. Tone-producing tools provide approximate hearing thresholds but have calibration and background noise issues. Speech and self-report tools are less affected by these issues but mostly do not provide an estimated pure tone audiogram. Predicting audiograms using filtered language-independent materials could be a universal solution.

Effectiveness and optimal duration of early intervention treatment in adult-onset psychosis: a randomized clinical trial.

BACKGROUND: Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention. METHODS: 360 psychosis patients aged 26-55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years. RESULTS: Compared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001-0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004-0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year. CONCLUSIONS: Specialized EI treatment for psychosis patients aged 26-55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.

The distinct associations of ingroup attachment and glorification with responses to the coronavirus pandemic: Evidence from a multilevel investigation in 21 countries.

While public health crises such as the coronavirus pandemic transcend national borders, practical efforts to combat them are often instantiated at the national level. Thus, national group identities may play key roles in shaping compliance with and support for preventative measures (e.g., hygiene and lockdowns). Using data from 25,159 participants across representative samples from 21 nations, we investigated how different modalities of ingroup identification (attachment and glorification) are linked with reactions to the coronavirus pandemic (compliance and support for lockdown restrictions). We also examined the extent to which the associations of attachment and glorification with responses to the coronavirus pandemic are mediated through trust in information about the coronavirus pandemic from scientific and government sources. Multilevel models suggested that attachment, but not glorification, was associated with increased trust in science and compliance with federal COVID-19 guidelines. However, while both attachment and glorification were associated with trust in government and support for lockdown restrictions, glorification was more strongly associated with trust in government information than attachment. These results suggest that both attachment and glorification can be useful for promoting public health, although glorification's role, while potentially stronger, is restricted to pathways through trust in government information.

Electron tomography of prolamellar bodies and their transformation into grana thylakoids in cryofixed Arabidopsis cotyledons.

The para-crystalline structures of prolamellar bodies (PLBs) and light-induced etioplast-to-chloroplast transformation have been investigated via electron microscopy. However, such studies suffer from chemical fixation artifacts and limited volumes of 3D reconstruction. Here, we examined Arabidopsis thaliana cotyledon cells by electron tomography (ET) to visualize etioplasts and their conversion into chloroplasts. We employed scanning transmission ET to image large volumes and high-pressure freezing to improve sample preservation. PLB tubules were arranged in a zinc blende-type lattice-like carbon atoms in diamonds. Within 2 h after illumination, the lattice collapsed from the PLB exterior and the disorganized tubules merged to form thylakoid sheets (pre-granal thylakoids), which folded and overlapped with each other to create grana stacks. Since the nascent pre-granal thylakoids contained curved membranes in their tips, we examined the expression and localization of CURT1 (CURVATURE THYLAKOID1) proteins. CURT1A transcripts were most abundant in de-etiolating cotyledon samples, and CURT1A was concentrated at the PLB periphery. In curt1a etioplasts, PLB-associated thylakoids were swollen and failed to form grana stacks. In contrast, PLBs had cracks in their lattices in curt1c etioplasts. Our data provide evidence that CURT1A is required for pre-granal thylakoid assembly from PLB tubules during de-etiolation, while CURT1C contributes to cubic crystal growth in the dark.

The reliability of symptom assessment by telepsychiatry compared with face to face psychiatric interviews.

INTRODUCTION: With the start of the COVID-19 pandemic, the various social distancing policies imposed have mandated psychiatrists to consider the option of using telepsychiatry as an alternative to face-to-face interview in Hong Kong. Limitations over sample size, methodology and information technology were found in previous studies and the reliability of symptoms assessment remained a concern. AIM: To evaluate the reliability of assessment of psychiatric symptoms by telepsychiatry comparing with face-to-face psychiatric interview. METHOD: This study recruited a sample of adult psychiatric patients in psychiatric wards in Queen Mary Hospital. Semi-structural interviews with the use of standardized psychiatric assessment scales were carried out in telepsychiatry and face-to-face interview respectively by two clinicians and the reliability of psychiatric symptoms elicited were assessed. RESULTS: 90 patients completed the assessments The inter-method reliability in Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Columbia Suicide Severity Rating Scale and Brief Psychiatric Rating Scale showed good agreement when compared with face-to-face interview. CONCLUSION: Symptoms assessment by telepsychiatry is comparable to assessment conducted by face-to-face interview.

Successful Treatment of Drug-Resistant Seizures Secondary to Ring 20 Mosaicism with Perampanel as an Add-On Antiepileptic Drug.

We report a girl with drug-resistant seizures, progressive behavioral changes, and cognitive decline. Investigations showed abnormal EEG with frequent high-voltage bifrontotemporal sharp and slow waves, especially during sleep. Seizures were difficult to control, despite the usage of various antiepileptic drugs. Perampanel as an add-on antiepileptic drug appeared efficacious. Due to the recognizable pattern of seizures and EEG findings, a karyotype study was performed which revealed 46 chromosomes with a ring 20 chromosome mosaicism. Ring 20 chromosome is associated with drug-resistant refractory seizures, cognitive decline, and behavioral problems. This case highlights the difficulty and challenge faced in managing drug-resistant refractory seizures associated with ring 20 chromosome. While ring 20 chromosome is often underdiagnosed, one should have a high index of awareness and suspicion of such rare epilepsy syndrome, so that an early diagnosis can be made.

Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.

U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.

Sex differences in symptom severity, cognition and psychosocial functioning among individuals with at-risk mental state for psychosis.

AIM: Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning. METHODS: One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains. RESULTS: Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning. CONCLUSIONS: This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.

Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2-25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing ≥20 kg) or 0·25 mg/kg (for individuals weighing <20 kg), or daily oral placebo (matched to risdiplam in colour and taste). Randomisation was conducted by permutated block randomisation with a computerised system run by an external party. Patients, investigators, and all individuals in direct contact with patients were masked to treatment assignment. The primary endpoint was the change from baseline in the 32-item Motor Function Measure total score at month 12. All individuals who were randomly assigned to risdiplam or placebo, and who did not meet the prespecified missing item criteria for exclusion, were included in the primary efficacy analysis. Individuals who received at least one dose of risdiplam or placebo were included in the safety analysis. SUNFISH is registered with ClinicalTrials.gov, NCT02908685. Recruitment is closed; the study is ongoing. FINDINGS: Between Oct 9, 2017, and Sept 4, 2018, 180 patients were randomly assigned to receive risdiplam (n=120) or placebo (n=60). For analysis of the primary endpoint, 115 patients from the risdiplam group and 59 patients from the placebo group were included. At month 12, the least squares mean change from baseline in 32-item Motor Function Measure was 1·36 (95% CI 0·61 to 2·11) in the risdiplam group and -0·19 (-1·22 to 0·84) in the placebo group, with a treatment difference of 1·55 (0·30 to 2·81, p=0·016) in favour of risdiplam. 120 patients who received risdiplam and 60 who received placebo were included in safety analyses. Adverse events that were reported in at least 5% more patients who received risdiplam than those who received placebo were pyrexia (25 [21%] of 120 patients who received risdiplam vs ten [17%] of 60 patients who received placebo), diarrhoea (20 [17%] vs five [8%]), rash (20 [17%] vs one [2%]), mouth and aphthous ulcers (eight [7%] vs 0), urinary tract infection (eight [7%] vs 0), and arthralgias (six [5%] vs 0). The incidence of serious adverse events was similar between treatment groups (24 [20%] of 120 patients in the risdiplam group; 11 [18%] of 60 patients in the placebo group), with the exception of pneumonia (nine [8%] in the risdiplam group; one [2%] in the placebo group). INTERPRETATION: Risdiplam resulted in a significant improvement in motor function compared with placebo in patients aged 2-25 years with type 2 or non-ambulant type 3 spinal muscular atrophy. Our exploratory subgroup analyses showed that motor function was generally improved in younger individuals and stabilised in older individuals, which requires confirmation in further studies. SUNFISH part 2 is ongoing and will provide additional evidence regarding the long-term safety and efficacy of risdiplam. FUNDING: F Hoffmann-La Roche.

Support care needs of people with hearing and vision impairment in dementia: a European cross-national perspective.

PURPOSE: Aging-related sensory impairments are among the most common and disabling comorbidities in people with dementia (PwD). This study explored the unmet support care needs (SCNs) from the perspectives of people with hearing and/or vision impairment in dementia (PwD), and their care partners in Europe. METHODS: This was a two-phase mixed methods study. We administered standardized questionnaires of SCNs and quality of life (QoL) to PwD with hearing and/or vision impairment (n = 97), and their care partners (n = 97) in the UK, France, and Cyprus. Next, a purposive sub-sample of 34 participants (PwD and care partners) participated as focus groups (FGs) or semi-structured interviews to explore their SCNs in depth. RESULTS: Over 94% of the participants reported unmet SCNs (median, 13 (range 5-23)). Nearly three-quarters reported SCNs in the moderate to high range, with the most prevalent unmet SCNs for PwD being in the psychological (>60%) and physical domains (>56%), followed by the need for health information (>46%). Emergent qualitative themes were: (1) the need for tailored support care interventions; (2) care burden, social isolation, and loneliness arising from the combined problems; (3) the need for adequate support from professionals from the different fields, including education around the use of sensory aids. Both study phases revealed that SCNs were highly individualized. CONCLUSIONS: This cross-national study revealed that PwD with sensory impairment and their care partners experience a wide range of unmet SCNs, the interactions between sensory impairments, SCNs and QoL are also complex. A tailored intervention could address these unmet SCNs, including additional support with sensory aids, psychological support, more information about concurrent impairments, and joined up health systems providing care.Implications for rehabilitationA majority of participants with combined age-related hearing, vision, and cognitive impairment had unmet SCNs.The needs of care partners including the risk of loneliness and social isolation, need to be considered.Individually tailored, specific interventions for hearing, vision, and cognitive impairment should incorporate physical and psychological support, as well as education.

Health-Promoting Behaviors, Risk Perceptions, and Attention to COVID-19-Related Information: Comparing People's Responses to the COVID-19 Pandemic Across Times of Chinese New Year and Summer 2020 in Hong Kong.

Background: Since the start of the COVID-19 pandemic, individuals have been encouraged to engage in health-promoting behaviors, namely actions taken to prevent infection and keep themselves healthy, such as maintaining social distancing. However, other factors, such as risk perception and feelings of fear, also might influence whether an individual takes such measures. This study compared people's responses to the pandemic in terms of their adoption of COVID-19 health-promoting behaviors, COVID-19 risk perceptions, and attention to COVID-19-related information during two periods: the 2020 Chinese New Year (CNY) in Hong Kong (HK), i.e., the very beginning of the COVID-19 outbreak (Time 1, T1), and summer 2020, i.e., before and during the third wave of COVID-19 infections in HK (Time 2, T2). Methods: Data were extracted from 180 HK participants, who were asked to recall and report their health-promoting behaviors, emotional and cognitive COVID-19 risk perceptions, and attention to COVID-19-related information during T1 and T2. A repeated-measures ANOVA series was conducted to investigate differences in public responses between the two aforementioned time points. Main Findings: After controlling for the effects from gender, age, and education levels, the participants reported practicing more infection-prevention behaviors, experiencing a lower level of fear as a psychological response, and paying less attention to COVID-19-related information during T2 than T1. Conclusions: This study addressed the need to monitor public responses to the COVID-19 pandemic, including changes in people's behaviors and psychological responses across time. The results also suggest that the HK public was steered toward striking a balance between strengthening their infection-prevention behaviors and reducing their fear of COVID-19 infection.