Development and acceptability of a brief, evidence-based Dementia Awareness for Caregivers course in low- and middle-income countries

BACKGROUND: Knowledge of and attitudes towards dementia vary across countries, and for caregivers in low- and middle-income countries (LMICs), access to information can be challenging. There is an urgent need for brief, easily accessible and culturally appropriate educational courses for caregivers of persons with dementia, providing much needed information whilst addressing important psychological concepts such as stigma. METHODS: An international and multidisciplinary team developed Dementia Awareness for Caregivers (DAC) courses in four stages: (1) scoping review and module agreement, (2) development of an International template (DAC-International) containing a standardised process for adding information, (3) development of local DACs using a standardised format and (4) acceptability of courses in Brazil, India and Tanzania. FINDINGS: The DAC-International was developed, comprising three modules: 'What is dementia?'; 'Positive engagement' and 'Caring for someone with dementia'. Three local versions were developed from this (DAC-Brazil, DAC-India and DAC-Tanzania), where additions of country-specific information included prevalent stereotypes and the addition of culturally relevant case studies. An initial field test was conducted in each country (n = 85), which indicated acceptability to participants. CONCLUSIONS: The methods used here resulted in culturally valid and acceptable educational courses for carers of people with dementia. Future work will consist of large-scale, formal evaluations and the development of additional local courses

Patient acceptable symptom state in scleroderma: results from the tocilizumab compared with placebo trial in active diffuse cutaneous systemic sclerosis

OBJECTIVES: Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. METHODS: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96, including if a current state would be acceptable over time as a yes vs no response and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included modified Rodnan skin score, HAQ disability index (HAQ-DI), physician and patient global assessments on a visual analogue scale, CRP and ESR. RESULTS: The placebo group consisted of 44 patients and the TCZ group had 43 patients. At baseline, 33% achieved a PASS for all three PASS questions, with the proportion increasing to 69, 71 and 78%, respectively, at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI and patient and physician global assessments visual analogue scales, which indicates expected improvements as PASS improved. The PASS question, 'Considering all of the ways your scleroderma has affected you, how acceptable would you rate your level of symptoms?' showed significant correlations with patient-reported outcomes and differentiating placebo vs TCZ at 48 weeks (P = 0.023). Conclusion: PASS may be used as a patient-centred outcome in SSc, especially as a 7-point Likert scale. Further validation is required to determine the utility as an outcome measure in trials and clinical practice

Optimized protocol for assay for transposase-accessible chromatin by sequencing (ATAC-seq) from Drosophila melanogaster brain tissue

Summary: Transposase-accessible chromatin by sequencing (ATAC-seq) has emerged as an advantageous technique to assess chromatin accessibility owing to the robustness of ''tagmentation'' process and a relatively faster library preparation. A comprehensive ATAC-seq protocol from Drosophila brain tissue is currently unavailable. Here, we have provided a detailed protocol of ATAC-seq assay from Drosophila brain tissue. Starting from dissection and transposition to amplification of libraries has been elaborated. Furthermore, a robust ATAC-seq analysis pipeline has been presented. The protocol can be easily adapted for other soft tissues. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial

BACKGROUND: Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis. METHODS: We did this double-blind, placebo-controlled study at 35 hospitals in Canada, France, Germany, the UK, and the USA. We enrolled adults with progressive systemic sclerosis of 5 or fewer years' duration from first non-Raynaud's sign or symptom. Patients were randomly assigned (1:1) to weekly subcutaneous tocilizumab 162 mg or placebo. The primary endpoint was the difference in mean change from baseline in modified Rodnan skin score at 24 weeks. This study is registered with ClinicalTrials.gov, number NCT01532869. FINDINGS: We enrolled 87 patients: 43 assigned to tocilizumab and 44 assigned to placebo. The least squares mean change in modified Rodnan skin score at 24 weeks was −3·92 in the tocilizumab group and −1·22 in the placebo group (difference −2·70, 95% CI −5·85 to 0·45; p=0·0915). The least squares mean change at 48 weeks was −6·33 in the tocilizumab group and −2·77 in the placebo group (treatment difference −3·55, 95% CI −7·23 to 0·12; p=0·0579). In one of several exploratory analyses, fewer patients in the tocilizumab group than in the placebo group had a decline in percent predicted forced vital capacity at 48 weeks (p=0·0373). However, we detected no significant difference in disability, fatigue, itching, or patient or clinician global disease severity. 42 (98%) of 43 patients in the tocilizumab group versus 40 (91%) of 44 in the placebo group had adverse events. 14 (33%) versus 15 (34%) had serious adverse events. Serious infections were more common in the tocilizumab group (seven [16%] of 43 patients) than in the placebo group (two [5%] of 44). One patient died in relation to tocilizumab treatment. INTERPRETATION: Tocilizumab was not associated with a significant reduction in skin thickening. However, the difference was greater in the tocilizumab group than in the placebo group and we found some evidence of less decline in forced vital capacity. The efficacy and safety of tocilizumab should be investigated in a phase 3 trial before definitive conclusions can be made about its risks and benefits