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.

This real-world analysis of opportunistic testing in patients with PCDs reports a 67% seropositive response rate after the first dose, 3 rising to 89% after the second dose despite extended dosing in our present cohort. Response rates and median titres remained lower than in healthy adults. 1,5 Nearly two-thirds of those seronegative after the first dose Correspondence e22

BackgroundEarly warning score (EWS) is a system that assists in the timely recognition of hospitalized patients outside critical care areas with potential or established critical illness at risk of deteriorating and who may be receiving suboptimal care. No such systems have been implemented in Portuguese National Health Service's wards. We performed a preliminary study to assess the potential outcome of applying the EWS in our hospital setting.MethodsAn observational retrospective study was conducted based on 100 patients assessed by the outreach team due to an acute event. The EWS was calculated a posteriori on three preceding periods from the acute deterioration (−12, −24, and −72 h).ResultsIn 35 patients, there was insufficient recording of vital signs. The final sample of 65 patients includes 62.0% men, and the mean age (±SD) was 67 ± 16 years old. Respiratory problems were the main cause of deterioration (44.6%). The EWS score increased from −72 to −12 h. More than half of cases (63.0%) were admitted into high care units, and their mean (±SD) score was higher in comparison to those remaining in general wards (Intermediate Care Units 3.75 ± 1.9, Intensive Care Units 4.2 ± 1.5, wards 3.5 ± 1.4). Score at −24 and −12 h seemed to predict length of stay (LoS; p < 0.05) and mortality, respectively. The EWS would have incremented early medical attention by 40.0% if a threshold of ≥3 was used.ConclusionsEWS systems are not widely used in Portuguese health service. Our data suggests that the EWS would allow early recognition for a higher number of patients in comparison to current ward care. Clinical worsening, lengths of stay, admission into high care units, and mortality may be predicted by the EWS. Prospective studies with multivariable analysis are needed to clarify the global outcome of the EWS implementation in national wards.