A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults.

INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.

Children And The Opioid Epidemic: Age-Stratified Exposures And Harms.

Using North Carolina Medicaid 2016-18 claims data, we found that approximately one in ten adolescents (10.8 percent) filled at least one opioid prescription per year. Dentists, advanced practice providers, and surgeons were common prescribers of opioids to children. In addition, half of children who experienced opioid-related adverse events had filled opioid prescriptions in the prior six months.

Retrospective review of biopsy results following percutaneous fixation of vertebral compression fractures.

BACKGROUND: Percutaneous vertebral body fixation has been found to provide pain relief and restoration of function for patients with compression fractures. Despite the prevalence of osteoporosis, there are a variety of aetiologies, such as lymphoma, myeloma or metastatic disease that may be responsible for the condition. In these instances, vertebral body biopsy can play an important role in determining fracture aetiology and assist in initiating concurrent medical treatment. MATERIALS AND METHODS: Between 2002 and 2005, 80 vertebral body biopsies were performed in conjunction with percutaneous augmentation procedures on 50 patients at our teaching institution. Eleven biopsies were performed during vertebroplasty and 69 were performed during kyphoplasty. The mean age at the time of procedure was 75.7 years. Eight patients were male and 42 were female. A pathologist interpreted all biopsy samples and all charts were reviewed examining past history, diagnoses prior to compression fracture, biopsy results and post-op conditions that developed or were diagnosed after surgery. RESULTS: All patients healed their compression fractures following surgery and no complications were experienced. Eleven patients had a diagnosis of osteoporosis prior to vertebral fracture, while 8 patients had a malignant condition initially suspected as being responsible for the compression fracture. Malignancy was identified in 4 patients, 3 of whom did not previously have such a diagnosis. In an additional 6 cases the suspected aetiology behind vertebral compression fracture was not confirmed by pathology. DISCUSSION: This study found a 20% prevalence of malignancy in our population, which is higher than other reports in the literature. Eight percent of the patients in this study were ultimately found to have a malignant aetiology behind their compression fracture, while in 18% of the cases the presumed aetiology was not confirmed on pathological examination. Compression fractures can be one of the most common manifestations of osteoporosis, but a variety of other conditions, including neoplastic processes may also be responsible. As a result, we recommend obtaining a vertebral body biopsy prior to every vertebral augmentation procedure.