Efficient strategies to contain the coronavirus disease 2019 (COVID-19) pandemic are peremptory to relieve the negatively impacted public health and global economy, with the full scope yet to unfold. In the absence of highly effective drugs, vaccines, and abundant medical resources, many measures are used to manage the infection rate and avoid exhausting limited hospital resources. Wearing masks is among the non-pharmaceutical intervention (NPI) measures that could be effectively implemented at a minimum cost and without dramatically disrupting social practices. The mask-wearing guidelines vary significantly across countries. Regardless of the debates in the medical community and the global mask production shortage, more countries and regions are moving forward with recommendations or mandates to wear masks in public. Our study combines mathematical modeling and existing scientific evidence to evaluate the potential impact of the utilization of normal medical masks in public to combat the COVID-19 pandemic. We consider three key factors that contribute to the effectiveness of wearing a quality mask in reducing the transmission risk, including the mask aerosol reduction rate, mask population coverage, and mask availability. We first simulate the impact of these three factors on the virus reproduction number and infection attack rate in a general population. Using the intervened viral transmission route by wearing a mask, we further model the impact of mask-wearing on the epidemic curve with increasing mask awareness and availability. Our study indicates that wearing a face mask can be effectively combined with social distancing to flatten the epidemic curve. Wearing a mask presents a rational way to implement as an NPI to combat COVID-19. We recognize our study provides a projection based only on currently available data and estimates potential probabilities. As such, our model warrants further validation studies.

ObjectivesTo determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement (2013), and any association with author, trial or journal factors.DesignMethodological study.Data sourcesMEDLINE, Embase and CENTRAL were electronically searched using optimised search strategies.Eligibility criteriaProtocols written for an RCT of living humans, published in full text in a peer-reviewed journal and published in the English language.Main outcomePrimary outcome was the overall proportion of checklist items which were adequately reported in RCT protocols published before and after the SPIRIT statement.Results300 RCT protocols were retrieved; 150 from the period immediately before the SPIRIT statement (9 July 2012 to 28 December 2012) and 150 from a recent period after the SPIRIT statement (25 January 2019 to 20 March 2019). 47.9% (95% CI, 46.5% to 49.3%) of checklist items were adequately reported in RCT protocols before the SPIRIT statement and 56.7% (95% CI, 54.9% to 58.5%) after the SPIRIT statement. This represents an 8.8% (95% CI, 6.6% to 11.1%; p<0.0001) mean improvement in the overall proportion of checklist items adequately reported since the SPIRIT statement. While 40% of individual checklist items had a significant improvement in adequate reporting after the SPIRIT statement, 11.3% had a significant deterioration and there were no RCT protocols in which all individual checklist items were complete. The factors associated with higher reporting quality of RCT protocols in multiple regression analysis were author expertise or experience in epidemiology or statistics, multicentre trials, longer protocol word length and publicly reported journal policy of compliance with the SPIRIT statement.ConclusionThe overall reporting quality of RCT protocols has significantly improved since the SPIRIT statement, although a substantial proportion of individual checklist items remain poorly reported. Continued and concerted efforts are required by journals, editors, reviewers and investigators to improve the completeness and transparency of RCT protocols.

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Background IMI2-PainCare-BioPain-RCT2 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on specific compartments of the nociceptive system that could serve to accelerate the future development of analgesics. IMI2-PainCare-BioPain-RCT2 will focus on human spinal cord and brainstem activity using biomarkers derived from non-invasive neurophysiological measurements. Methods This is a multisite, single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Neurophysiological biomarkers of spinal and brainstem activity (the RIII flexion reflex, the N13 component of somatosensory evoked potentials (SEP) and the R2 component of the blink reflex) will be recorded before and at three distinct time points after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol), and placebo, given as a single oral dose in separate study periods. Medication effects on neurophysiological measures will be assessed in a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin), and in a non-sensitized normal condition. Patient-reported outcome measures (pain ratings and predictive psychological traits) will also be collected; and blood samples will be taken for pharmacokinetic modelling. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between the two primary endpoints, namely the percentage amplitude changes of the RIII area and N13 amplitude under tapentadol. Remaining treatment arm effects on RIII, N13 and R2 recovery cycle are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modelling are exploratory. Discussion The RIII component of the flexion reflex is a pure nociceptive spinal reflex widely used for investigating pain processing at the spinal level. It is sensitive to different experimental pain models and to the antinociceptive activity of drugs. The N13 is mediated by large myelinated non-nociceptive fibers and reflects segmental postsynaptic response of wide dynamic range dorsal horn neurons at the level of cervical spinal cord, and it could be therefore sensitive to the action of drugs specifically targeting the dorsal horn. The R2 reflex is mediated by large myelinated non-nociceptive fibers, its circuit consists of a polysynaptic chain lying in the reticular formation of the pons and medulla. The recovery cycle of R2 is widely used for assessing brainstem excitability. For these reasons, IMI2-PainCare-BioPain-RCT2 hypothesizes that spinal and brainstem neurophysiological measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification. Trial registration This trial was registered on 02 February 2019 in EudraCT (2019-000755-14).

Objectives To investigate the effects of sodium tetradecyl sulphate and polidocanol on fibrinolytic potential of sclerosant-incubated clots. Methods Serial dilutions of sodium tetradecyl sulphate and polidocanol were incubated with platelet poor plasma and whole blood samples. Rotational thromboelastometry was used to determine the lysis of sclerosant-incubated clots in whole blood. Fibrin generation and fibrinolysis were quantified using an overall haemostatic potential assay on platelet poor plasma. Results Rotational thromboelastometry analysis of whole blood revealed increased maximum lysis in the presence of sodium tetradecyl sulphate but decreased maximum lysis at low concentrations of polidocanol. Clots generated using platelet poor plasma in the overall haemostatic potential assay demonstrated no significant change in fibrinolysis for both sclerosants at all concentrations measured. Discussion Sodium tetradecyl sulphate and polidocanol produce differing effects on the fibrinolytic potential depending on sample type and concentration. In whole blood, sodium tetradecyl sulphate produces clots more sensitive to lysis while polidocanol produced fibrinolytic-resistant clots.