Axel Schaefer

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. METHODS: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. RESULTS: A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

ABSTRACT Background BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable. Methods In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 ≥16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 µg BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination. Results BNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0-93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%-100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% (95% CI 80.3−99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed. Conclusion With up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. ( ClinicalTrials.gov number, NCT04368728 )

BACKGROUND: Chronic pain including migraine is associated with structural and functional changes in the somatosensory cortex. Previous reports proposed two-point discrimination (TPD) as a measurement for cortical alterations. Limited evidence exists for tactile acuity in the neck and no data is available for migraine. METHODS: To introduce a standardized protocol for the measurement of TPD in the upper cervical spine, 51 healthy participants were investigated with a newly developed paradigm which was evaluated for intra-rater reliability. The same protocol was applied by two further examiners to 28 migraine patients and 21 age-, and gender-matched healthy controls to investigate inter-rater reliability and between group differences. RESULTS: = 0.75). Migraine patients had larger TPD thresholds (26.86 ± 7.21) than healthy controls (23.30 ± 6.17) but these became only statistically significant for the right side of the neck (p = 0.02). There was a significant, moderate association with age for the right side (r = 0.42 p = 0.002, n = 51), and less strong association for the left side (r = 0.34, p = 0.14) in healthy individuals. TPD did not correlate with headache days per month or the dominant headache side in migraine patients. CONCLUSIONS: Surprisingly, migraine patients showed increased TPD thresholds in the upper cervical spine interictally. Although a body of evidence supports that hypersensitivity is part of the migraine attack, the current report indicates that interictally, migraine patients showed worse tactile acuity similar to other chronic pain populations. This has been hypothesized to indicate structural and functional re-organisation of the somatosensory cortex.

BACKGROUND: Neck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP. METHODS: In a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study. RESULTS: The primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel. CONCLUSIONS: DDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01335724.

This randomized, placebo-controlled, double-blind trial was conducted to assess the efficacy and safety of ivy leaves cough liquid in the treatment of acute cough. A total of 181 adult patients with acute cough were treated with either ivy leaves cough liquid containing EA 575® or with placebo three times a day for one week. The primary efficacy outcome was cough severity (CS) assessed by Visual Analogue Scale (VAS) over the whole treatment period (area-under-the-curve (AUC0-168 h) over 7 days (visit (V)1, V2, V3, V4, and V5). The secondary endpoints were defined as the CS assessed by VAS over the whole observation period (V1 - V6) and by Bronchitis Severity Score (BSS) and Verbal Category Descriptive (VCD) score. The evaluation of the VAS, BSS and VCD score revealed that subjects treated with ivy leaves cough liquid showed statistically significant and clinically relevant reductions in CS, severity of symptoms associated with cough and bronchitis compared to the placebo group. Furthermore, a remarkable early onset of efficacy was observed as significant reductions of cough severity were detected within 48 hours after the first drug intake. At all following visits and even 7 days after the end of treatment (V6) this significant treatment advantage was detected in comparison to placebo. All adverse events (AEs) in this clinical trial were non-serious, mild or of moderate severity and not drug-related. This clinical trial proved consistent superiority of the ivy leaves cough liquid treatment versus placebo and confirmed the EA 575® preparation to be a safe and efficacious option for the treatment of acute cough.