Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50-75 years: a phase 1/2, open-label, randomised trial.

BACKGROUND: Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults. METHODS: This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50-75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing. FINDINGS: Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6-3·6; Darwin) and 3·1 (2·6-3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7-4·1; Darwin) and 4·2 (3·4-5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9-4·0; Darwin), 4·5 (3·6-5·5; Newcastle), and 5·1 (4·2-6·2; Hong Kong) for mRNA-1012 50·0 µg; and 2·6 (2·2-3·1; Darwin), 3·7 (3·0-4·6; Newcastle), and 4·1 (3·3-5·1; Hong Kong) for mRNA-1012 62·5 µg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria. INTERPRETATION: These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage. FUNDING: Moderna.

Sideline and event management in golf.

Golf has great popularity as a spectator sport, as well as a participation sport. Providing coverage for golf events can range from mass event coverage for large professional tournaments to provision of injury care at local golf events. This article provides a brief introduction to the game of golf for those unfamiliar with its play, an overview of the types of injuries seen, and consideration in providing care for a variety of golf competitions.

Lower back pain in golf: a review.

Back pain is one of the most common reasons cited for patients to see a physician. It also is the most frequently reported injury in golf. Any physician caring for golfers must therefore understand common causes of back pain, its treatment, and prevention strategies to reduce the burden of future injury.

Ice hockey: a team physician's perspective.

Ice hockey is an exciting sport that is growing in popularity in the United States. Injuries are a common part of the sport, with more injuries occurring in games compared with practice. Higher levels of competition have been shown to correlate with increased frequency of injury. Most frequently, injuries occur to the face, head, and neck, including concussions, contusions, lacerations, and dental injury. Lower extremity injuries include medial collateral ligament injury, meniscus tear, and high ankle sprains. Upper extremity injuries include acromioclavicular joint injury, glenohumeral dislocation, and various contusions and sprains. Groin and lower abdominal strains also are common. Women's hockey participation is increasing, with data that suggest injuries similar to those seen in men's hockey.

Upper extremity injuries in golf.

Golf is an asymmetric sport with unique patterns of injury depending upon the skill level. Higher handicap players typically experience injuries that result from swing mechanics, whereas lower handicap and professional players have overuse as the major cause of their injuries. The majority of shoulder injuries affecting golfers occur in the nondominant shoulder. Common shoulder injuries include subacromial impingement, rotator cuff pathology, glenohumeral instability, and arthritis involving the acromioclavicular and/or glenohumeral joints. Lead arm elbow pain resulting from lateral epicondylosis (tennis elbow) is the leading upper extremity injury in amateur golfers. Tendon injury is the most common problem seen in the wrist and forearm of the golfer. Rehabilitation emphasizing improvement in core muscle streng is important in the treatment of golf injury. Emerging treatments for tendinopathy include topical nitrates, ultrasound-guided injection of therapeutic substances, and eccentric rehabilitation. There is evidence supporting physiotherapy, and swing modification directed by a teaching professional, for treatment of upper extremity golf injuries. This article focuses on upper extremity injuries in golf, including a discussion of the epidemiology, causes, diagnosis, treatment, and prevention of injuries occurring in the shoulder, elbow, wrist, and hand.

Comparison of injury-tracking programs.

Injury-tracking software is becoming a necessity in the athletic training room to organize care and meet requirements for record-keeping. A variety of competing products is available, including workstation, local network, and Internet-based programs. Most of these systems are commercially available, while the NCAA Internet-based system is available for member institutions at no cost. A few of the injury-tracking systems have gained wider use and are reviewed here.

When golf hurts: musculoskeletal problems common to golfers.

Golfers most frequently report injuries to the low back, nondominant shoulder, and elbow. Injury patterns differ between elite and recreational golfers; professional and elite golfers tend to experience golf injury related to overuse while amateur golfers may experience injury related to adverse swing technique and overuse. Therapeutic interventions should include assessment and treatment of deficiencies in the kinetic chain and professional instruction to modify swing technique. Changes in the swing may include instruction in a more efficient technique or shortening the swing to decrease biomechanical forces affecting the injured area.

Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are standard therapy for osteoarthritis (OA). Topically applied NSAIDs reduce systemic exposure compared with oral NSAIDS, and European guidelines recommend their use. The NSAID diclofenac is available in a range of topical formulations. Diclofenac 1% gel and 1.5% four times daily and 2% twice daily (BID) solutions are approved to reduce pain from OA of the knee(s). The objective of this study was to investigate the efficacy and safety of diclofenac sodium 2% topical solution BID versus vehicle control solution for treating pain associated with OA of the knee. RESEARCH DESIGN AND METHODS: A phase II, 4 week, randomized, double-blind, parallel-group, two-arm, vehicle-controlled study compared pain relief with diclofenac sodium 2% topical solution versus control (vehicle only) in patients aged 40 to 85 years with radiographically confirmed primary OA of the knee. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01119898. MAIN OUTCOME MEASURES: The primary efficacy outcome was change from baseline to the final visit in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes included additional WOMAC subscales and patient global assessment of OA. Treatment-emergent adverse events (TEAEs), skin irritation, and vital signs were assessed and collected throughout the study. RESULTS: Of 260 patients randomized, 259 received ≥1 dose of study drug. Significantly greater reductions in least-squares mean (standard error) WOMAC pain scores were observed for diclofenac-treated (-4.4 [0.4]) versus vehicle-treated patients (-3.4 [0.4]) at the final visit (p = 0.040). The most commonly reported TEAEs were administration site conditions. The vehicle-treated group experienced slightly more TEAEs than the active treatment group (38.8% vs. 31.5%). No serious adverse events were reported. CONCLUSIONS: Administration of diclofenac sodium 2% topical solution BID resulted in significantly greater improvement in pain reduction in patients with OA of the knee versus vehicle control and was generally well tolerated.