Efficacy, effectiveness and immunogenicity of reduced HPV vaccination schedules: A review of available evidence.

Background: Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. Objective: The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. Methods: To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Results: Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. Conclusion: While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.

Pandemic Risk Assessment for Swine Influenza A Virus in Comparative In Vitro and In Vivo Models.

Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify which animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019 (H1N2), using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host, with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest that the selection of models is important for meaningful risk assessment.

Republication of "Most Readmissions Following Ankle Fracture Surgery Are Unrelated to Surgical Site Issues: An Analysis of 5056 Cases".

Background: Ankle fracture surgeries are generally safe and effective procedures; however, as quality-based reimbursement models are increasingly affected by postoperative readmission, we aimed to determine the causes and risk factors for readmission following ankle fracture surgery. Methods: Ankle fracture cases were identified from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program from 2013 to 2014. Demographics, comorbidities, and fracture characteristics were collected. Rates of 30-day adverse events and readmissions were determined as well as the causes for readmission. Multivariable logistic regression analyses were performed to identify risk factors associated with having any adverse events and being readmitted within 30 days of surgery. Results: There were 5056 patients included; 167 (3.3%) were open fractures. The rate of any postoperative adverse event was 5.2%. There were 116 unplanned readmissions, with a readmission rate of 2.3%. Of the 116 unplanned readmissions, 49 (42.2%) were for reasons related to the surgery or surgical site, with the most common causes being deep surgical site/hardware infections (12.9%), superficial site infections (11.2%), and wound disruption (6.9%). Most readmissions were for reasons unrelated to the surgical site (51.7%), including cardiac disorders (8.6%), pulmonary disorders (7.8%), and neurological/psychiatric disorders (6.9%). The cause of readmission was unknown for 6% of readmissions. With multivariable logistic regression, the strongest risk factors for readmission were a history of pulmonary disease (odds ratio [OR], 2.29), American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.28), and open fractures (OR, 2.04) (all P < .05). Conclusion: In this cohort of 5056 ankle fracture cases, 2.3% of patients were readmitted within 30 days, with at least 51.7% of all unplanned readmissions due to causes unrelated to the surgery or surgical site. Predictors of readmission included a history of pulmonary disease, higher ASA class, and open fractures. Based on these findings, we advocate close medical follow-up with nonorthopaedic providers after discharge for high-risk patients. Level of Evidence: Level III.

The Use of Patient-Reported Outcomes Measurement Information System in Spine: A Systematic Review.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to provide an easily administered patient-outcome questionnaire that was adaptable to a variety of medical and surgical subspecialties. Numerous authors have examined the effectiveness of PROMIS in various areas of spine surgery. Our goal was to systematically review PROMIS scores compared with legacy patient-reported outcomes measures (PROMs) in spinal surgery and spine pathology. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed, yielding 254 unique studies reporting on "PROMIS" in "spine." Each study was independently reviewed. A total of 16 studies were selected for inclusion. RESULTS: The pooled sample size yielded a total of 4268 patients. In the cervical population, PROMIS physical function (PF; |r| = .47-.87, pain intensity (PIn; |r| = .61-.74), pain interference (PIf; |r| = .65-.88), and pain behavior (PB; |r| = .59-.74) correlated with the Neck Disability Index (NDI). PROMIS PF also strongly correlated with the modified Japanese Orthopaedic Association scale (mJOA; |r| = .61-.72). Among patients with lumbar pathology and adult spinal deformities, PROMIS PF (|r| = .53-.85), PIn (|r| = .73-.78), PIf (|r| = .59-.89), and PB (|r| = .58-.82) strongly correlated with the Oswestry Disability Index (ODI). PF (|r| = .51-.78), PIf (|r| = .60-.70), and anxiety (|r| = .73) also strongly correlated with the Scoliosis Research Society (SRS)-22 and SRS-30. When comparing measures of global health, PROMIS PF was strongly correlated with the Short Form (SF)-12 and SF-36 (|r| = .50-.85). On average, all PROMIS domains required less time to complete (49.6-56 seconds) than the ODI (176 seconds), NDI (190.3 seconds), SF-12 (214 seconds), and SF-36 physical function domains (99 seconds). The responsiveness of the PROMIS PF, PIf, and PB was comparable to that of legacy measures ODI, NDI, and SF-12. CONCLUSIONS: The PROMIS PF, PIn, PIf, and PB demonstrated moderate to strong correlations with NDI, mJOA, ODI, SRS, and SF-12 measures in various populations of spine patients. All PROMIS domains had decreased time to completion and similar responsiveness compared with legacy measures. LEVEL OF EVIDENCE: 2. CLINICAL RELEVANCE: These results highlight the potential of PROMIS as a valid and reliable tool to assess patient-reported outcomes in spinal surgery patients and support more widespread use of PROMIS in spine.

Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Next to progressive airway disease, CF is also associated with intestinal inflammation and dysbiosis. Ivacaftor, a CFTR potentiator, has improved pulmonary and nutritional status but its effects on the intestinal microbiota and inflammation are unclear. Hence, we assessed the changes on the intestinal microbial communities (16S rRNA variable 3 gene region) and inflammatory markers (calprotectin and M2-pyruvate kinase [M2-PK]) in 16 CF individuals (8 children and 8 adults) before and after (median 6.1 months) ivacaftor. Stool calprotectin significantly decreased following ivacaftor (median [IQR]: 154.4 [102.1-284.2] vs. 87.5 [19.5-190.2] mg/kg, P = 0.03). There was a significant increase in Akkermansia with ivacaftor. Increased abundance of Akkermansia was associated with normal stool M2-PK concentrations, and decreased abundances of Enterobacteriaceae correlated with decreased stool calprotectin concentrations. In summary, changes in the gut microbiome and decrease in intestinal inflammation was associated with Ivacaftor treatment among individuals with CF carrying at least one gating CFTR mutation. Thus, CFTR-modifying therapy may adequately improve the aberrant pathophysiology and milieu of the CF gut to favor a more healthy microbiota, which in turn reduces intestinal inflammation.