clinicaltrials.gov Identifier: NCT01951625.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

PATENT PLUS evaluated the safety and efficacy of riociguat in combination with sildenafil in pulmonary arterial hypertension patients.Patients receiving sildenafil (20 mg three times daily) were randomised to placebo or riociguat (up to 2.5 mg three times daily) for 12 weeks. The primary outcome was maximum change in supine systolic blood pressure (SBP) from baseline within 4 h of dosing. Secondary objectives comprised additional blood pressure, heart rate and exploratory efficacy variables, and safety. Patients could enter a long-term extension (LTE), where all patients received riociguat plus sildenafil.There was no difference in maximum change in supine SBP from baseline within 4 h between the riociguat (n=12) (mean±SD baseline: -20.2±15.3 mmHg; week 12: -20.7±18.0 mmHg) and placebo groups (n=6) (-7.6±3.9 and -20.2±12.9 mmHg, respectively). Changes in standing SBP and supine or standing diastolic blood pressure were also not different. Combination therapy showed no favourable effects on exploratory clinical parameters, including haemodynamics and exercise capacity. In the LTE, there were high rates of discontinuation due to hypotension and three (18%) deaths (not considered study drugrelated by the investigator).There were potentially unfavourable safety signals with sildenafil plus riociguat and no evidence of a positive benefit/risk ratio. Concomitant use of riociguat with phosphodiesterase-5 inhibitors is therefore contraindicated. @ERSpublications Sildenafil+riociguat in PAH: no evidence of a positive benefit/risk ratio and potentially unfavourable safety signals

BackgroundThe search for disease-modifying treatments for Parkinson's disease advances, however necessary markers for early detection of the disease are still lacking. There is compelling evidence that changes of postural stability occur at very early clinical stages of Parkinson's disease, making it tempting to speculate that changes in sway performance may even occur at a prodromal stage, and may have the potential to serve as a prodromal marker for the disease.Methodology/Principal FindingsBalance performance was tested in 20 individuals with an increased risk of Parkinson's disease, 12 Parkinson's disease patients and 14 controls using a cross-sectional approach. All individuals were 50 years or older. Investigated groups were similar with respect to age, gender, and height. An accelerometer at the centre of mass at the lower spine quantified sway during quiet semitandem stance with eyes open and closed, as well as with and without foam. With increasing task difficulty, individuals with an increased risk of Parkinson's disease showed an increased variability of trunk acceleration and a decrease of smoothness of sway, compared to both other groups. These differences reached significance in the most challenging condition, i.e. the eyes closed with foam condition.Conclusions/SignificanceIndividuals with an increased risk of Parkinson's disease have subtle signs of a balance deficit under most challenging conditions. This preliminary finding should motivate further studies on sway performance in individuals with an increased risk of Parkinson's disease, to evaluate the potential of this symptom to serve as a biological marker for prodromal Parkinson's disease.