Recreational runners with Achilles tendinopathy have clinically detectable impairments: A case-control study

ObjectivesTo confirm what impairments are present in runners with Achilles tendinopathy (AT) and explore the variance of AT severity in an adequately powered study.DesignCase-control study.SettingTwo private physiotherapy clinics in Australia and Spain.ParticipantsForty-four recreational male runners with AT and 44 healthy controls matched by age, height, and weight.Main outcome measuresDemographics, activity (IPAQ-SF), pain and function (VISA-A), pain during hopping (Hop pain VAS), hopping duration, psychological factors (TSK-11, PASS20), and physical tests regarding lower-limb maximal strength and endurance.ResultsBody mass index (BMI), activity, VISA-A, pain, and duration of hopping, TSK-11, PASS20, standing heel raise to failure, seated heel raise and leg extension 6RM, hip extension and abduction isometric torque were significantly different between groups (P < 0.05) with varied effect sizes (V = 0.22, d range = 0.05–4.18). 46% of AT severity variance was explained by higher BMI (β = −0.41; p = 0.001), weaker leg curl 6RM (β = 0.32; p = 0.009), and higher pain during hopping (β = −0.43; p = 0.001).ConclusionRunners with AT had lower activity levels, lower soleus strength, and were less tall. BMI, pain during hopping, and leg curl strength explained condition severity. This information, identified with clinically applicable tools, may guide clinical assessment, and inform intervention development.     

Safety and immunogenicity of Px563L,a recombinant anthrax vaccine candidate,in a two-dose regimen for post-exposure prophylaxis in healthy adults

Px563L is a next-generation anthrax vaccine candidate consisting of a protein subunit, mutant recombinant protective antigen SNKE167-ΔFF-315-E308D (mrPA), and liposome-embedded monophosphoryl lipid A (MPLA) adjuvant. Px563L has the potential to deliver an improved safety and immunogenicity profile relative to the currently licensed vaccine, which is produced from filtered B. anthracis culture supernatants.We conducted a Phase 1, double–blind, placebo–controlled, dose–escalation study in 54 healthy subjects to evaluate Px563L at 3 dose levels of mrPA (10, 50, and 80 mcg). For each dose level, 18 subjects were randomized in an 8:8:2 ratio to Px563L (mrPA with adjuvant), RPA563 (mrPA only) or placebo (saline). Each subject received an intramuscular (IM) injection on Day 0 and Day 28. Primary safety and immunogenicity analysis was conducted after all subjects completed the Day 70 visit, a duration deemed clinically relevant for post-exposure prophylaxis. Long-term safety was assessed through Day 393.Vaccinations with Px563L at all dose levels were well-tolerated. There were no serious adverse events or adverse events (AE) leading to early withdrawal. In all treatment groups, most AEs were due to injection site reactions, and all AEs at the 10 and 50 mcg dose levels were mild. For the primary immunogenicity endpoint (protective toxin neutralizing antibody 50% neutralization factor [TNA NF₅₀]), titers started to increase significantly after the second administration of Px563L, from Day 35 through Day 70, with the geometric mean and lower bound of the 95% confidence interval exceeding 0.56, a threshold correlating with significant survival in animal models of anthrax exposure.In conclusion, Px563L, administered as two IM doses 28 days apart, was well-tolerated and elicited a protective antibody response starting at seven days after the second vaccination. These findings support the continued development of Px563L in a two-dose regimen for anthrax post-exposure prophylaxis. ClinicalTrials.gov identifier NCT02655549.     

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.