Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

Correction to: Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Journal of Neurology - The original version of this article unfortunately contained a mistake.     

Pre-marital predictors of marital violence in the WHO World Mental Health (WMH) Surveys

Social Psychiatry and Psychiatric Epidemiology - Intimate partner violence (IPV) is a pervasive public health problem. Existing research has focused on reports from victims and few studies have...     

Depression,Is It Treatable in Adults Utilising Dietary Interventions? A Systematic Review of Randomised Controlled Trials

This systematic literature review examined whole food or whole diet interventions to treat depression. The inclusion criteria encompassed adults, depression, a recognized depression scale and a whole food or diet intervention. APA PsychINFO, CINAHL, the Cochrance Central Register of Controlled Trails, MEDLINE and Scopus were searched for original research addressing diet as a treatment for depression in adult populations. The quality of the study was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. Seven studies; with 49,156 participants; met the eligibility criteria. All these studies found positive outcomes with depression levels decreasing after dietary intervention. The calculated effect size varied from small (Cohen’s d = 0.32) to very large (Cohen’s d = 1.82). The inconsistent nature of the studies limited the synthesis of the data. Recommendations are provided to enhance future study design and measurement outcomes. Overall, the findings show a positive result for diets that promote an increased intake of fresh produce, wholegrains, low-fat dairy and lean protein sources, while also decreasing the intake of processed and high-fat foods. No funding was provided for this review. The protocol for this review is registered with PROSPERO (CRD42020210426).