Objective:To determine whether probiotics are effective for constipation, a common and often difficult-to-treat problem, in Parkinson’s disease (PD).Methods:In this double-blind, randomized placebo-controlled single-centre trial, 280 PD patients were screened and 72 eligible patients were block-randomized (1:1) to receive either multi-strain probiotics capsules (n=34), or identical-appearing placebo (n=38), for four weeks. The primary endpoint was the change in the average number of spontaneous bowel movements (SBM) per week during the last two weeks of intervention, compared with the two-week pre-intervention phase, recorded by daily stool diary. Secondary outcome measures included changes in stool consistency, constipation severity score, and quality of life related to constipation. Satisfaction with intervention received was assessed. Change in levels of fecal calprotectin, a marker of intestinal inflammation, was an exploratory outcome.Results:SBM increased by 1.0±1.2/week after treatment with probiotics, and decreased by 0.3±1.0/week in the placebo group (mean difference 1.3, 95%CI: 0.8-1.8, P<0.001). Significant improvements were also seen for secondary outcomes after correction for multiple comparisons, including stool consistency (P=0.009) and quality of life related to constipation (P=0.001). In the treatment group, 65.6% reported satisfaction with the intervention, vs. only 21.6% in the placebo group (P<0.001). One patient (2.9%) in the treatment group withdrew due to a non-serious adverse event. Fecal calprotectin did not change significantly during the study.Conclusions:Multi-strain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.Classification of evidence:This study provides Class I evidence that for people with PD, multi-strain probiotics significantly increased the average number of spontaneous bowel movements per week.Clinicaltrials.gov identifier:NCT03377322

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Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.