Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P50.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression

Analysis of kidney and liver exchange transplantation in India (2000–2025): a multicentre, retrospective cohort studyResearch in context

Summary: Background: In India, where deceased organ donation rates are relatively low, living donor transplantation programmes face challenges due to ABO incompatibility and sensitisation. Approximately one-third of healthy, willing living donors are incompatible with their intended recipients due to these factors. No large-scale data are currently available on kidney exchange (KE) or liver exchange (LE) transplants in low- and middle-income countries, including India. Methods: We conducted a multicentre, retrospective cohort study including KE (2000–2024) from 65 centres and LE (2007–2025) from 7 centres across India. The living donors were near-related donors without altruistic and deceased donors. Demographic and clinical data of both donors and recipients were included in the study. The reasons for KE/LE, post-transplant outcomes with respect to patient and graft survival, rejection episodes, and donor outcomes were analysed. Kidney allocation system guidelines were: (i) Thorough pre-transplant work-up of DRP was completed before allocation to avoid chain collapse. (ii) A policy of non-anonymous allocation was practised (in contrast to anonymous allocation in high-income countries), where pairs can create a rapport during evaluation and surgery. (iii) Simple two-way exchanges, and simultaneous surgeries were considered for less experienced transplant centres in order to avoid donor renege. Findings: A total of 1839 KE and 259 LE transplants were included in the study. The distribution of KE transplants included, 1594 (87%), 147 (8%), 44 (2%), 20 (1%), 24 (1%), and 10 (0.5%) transplants from 2-way, 3-way, 4-way, 5-way, 6-way and 10-way KE, respectively. Reasons for joining KE in transplanted pairs were ABO incompatibility 1610 (87%), compatible pairs 126 (7%), and sensitisation 103 (6%). There was notable gender imbalance, as more males were KE recipients 1504 (82%) and more females were donors 1469 (80%). The majority of LE were 2-way swaps (125 two-way vs. 3 three-way swaps), predominately involving male recipients (222 male vs. 37 females) and for ABO incompatibility. Interpretation: Our largest-to-date cohort study supports that swap transplants are medically simple, but logistically complex. Access to KE or LE was unequally distributed and likely under-used. If replicated, our experience could increase access to transplants and help combat the looming threat of commercial transplants. Funding: None