Summary Background Administration of vaccines by needle-free technology such as jet injection might offer an alternative to needles and syringes that avoids the issue of needle phobia and the risk of ...needle-stick injury. We aimed to assess the immunogenicity and safety of trivalent influenza vaccine given by needle-free jet injector compared with needle and syringe. Methods For this randomised, comparator-controlled trial, we randomly assigned (1:1) healthy adults (aged 18–64 years) who attended one of four employee health clinics in the University of Colorado health system, with stratification by site, to receive one dose of the trivalent inactivated influenza vaccine Afluria given either intramuscularly with a needle-free jet injector (Stratis; PharmaJet, Golden, CO, USA) or with needle and syringe. Randomisation was done with a computer-generated randomisation schedule with a block size of 100. Because of the nature of the study, masking of participants was not possible. Immunogenicity was assessed by measurement of the hemagglutination inhibition antibody titres in serum for the three viral strains included in the vaccine. We included six coprimary endpoints: three strain-specific geometric mean titre ratios and the absolute differences in three strain-specific seroconversion rates. The immune response of the jet injector group was regarded as non-inferior to that of the needle and syringe group if both the upper bound of each of the three 95% CIs for the strain-specific geometric mean titre ratios was 1.5 or less, and the upper bound of the three 95% CIs for the strain-specific seroconversion rate differences was less than 10 percentage points. We used t test for group comparison. This study is registered with ClinicalTrials.gov , number NCT01688921. Findings During the 2012–13 influenza season of the northern hemisphere, we allocated 1250 participants to receive vaccination by needle-free jet injector (n=627) or needle and syringe (n=623). In the intention-to-treat immunogenicity population, all participants with two serum samples were included (575 in the jet injector group and 574 in the needle and syringe group). The immune response to Afluria when given by needle-free jet injector met the criteria for non-inferiority for all six coprimary endpoints. The jet injector group met the geometric mean titre criterion for non-inferiority for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI for the geometric mean titre ratios were 1·10 for A/H1N1, 1·17 for A/H3N2, and 1·04 for B strains). The jet injector group met the seroconversion rate criterion for non-inferiority for the A/H1N1, A/H3N2, and B strains (upper bound of the 95% CI of the seroconversion rate differences were 6·0% for A/H1N1, 7·0% for A/H3N2, and 5·7% for B strains). We recorded serious adverse events in three participants, none of which were study related. Interpretation The immune response to influenza vaccine given with the jet injector device was non-inferior to the immune response to influenza vaccine given with needle and syringe. The device had a clinically acceptable safety profile, but was associated with a higher frequency of local injection site reactions than was the use of needle and syringe. The Stratis needle-free jet injector device could be used as an alternative method of administration of Afluria trivalent influenza vaccine. Funding Biomedical Advanced Research and Development Authority (BARDA), PATH, bioCSL, and PharmaJet.
Abstract Objectives To identify a biomarker panel with sufficient sensitivity and negative predictive value to identify children with abdominal pain at low risk for acute appendicitis in order to ...avoid unnecessary imaging. Methods We prospectively enrolled 503 subjects aged two to 20 years with < 72 hours of abdominal pain consistent with appendicitis. Blood samples from each patient were analyzed for CBC, differential, and 5 candidate proteins. Biomarker values were evaluated using principal component, recursive partitioning and logistic regression to select the combination that best discriminated between those subjects with and without disease. Results The prevalence of acute appendicitis was 28.6%. A mathematical combination of three inflammation-related markers in a panel comprised of white blood cell count (WBC), C-reactive protein (CRP), and myeloid-related protein 8/14 complex (MRP 8/14) provided the best discrimination. This panel exhibited a sensitivity of 96.5% (95% CI, 92-99%), a negative predictive value of 96.9% (95% CI, 93-99%), a negative likelihood ratio of 0.08 (95% CI, 0.03- 0.19), and a specificity of 43.2% (95% CI, 38-48%) for acute appendicitis. Sixty of 185 CT scans (32.4%) were done for patients with negative biomarker panel results which, if deferred, would have reduced CT utilization at initial presentation by one third at the cost of missing five of 144 (3.5%) patients with appendicitis. Conclusion This panel may be useful in identifying pediatric patients with signs and symptoms suggestive of acute appendicitis who are at low risk and can be followed clinically, potentially sparing them exposure to the ionizing radiation of CT.
Abstract Background The diagnosis of pediatric acute appendicitis can be difficult. While scoring systems such as the Pediatric Appendicitis Score (PAS) are helpful, they lack adequate sensitivity ...and specificity as stand-alone diagnostics. When utilized for risk stratification, they often result in large percentages of moderate risk patients requiring further diagnostic evaluation. Methods We applied a biomarker panel (the APPY 1™ Test) that has high sensitivity and negative predictive value to patients with PAS in the moderate risk range Larson et al. (2011, 2015), Brenner et al. (2001), Gardner et al. (2007), Kocher et al. (2012) 20-24 , and reclassified those patients with a negative result to the low risk group. We compared the specificity, sensitivity, and negative predictive value (NPV), of the original and reclassified low risk groups at several different PAS low risk cutoffs. Results The application of a negative biomarker panel to a group of patients with a moderate risk for appendicitis (PAS score 3–7) resulted in 4 times more patients (586 vs. 145) being safely classified as low risk. Reclassification increased the overall specificity, or the proportion of patients without appendicitis who were correctly identified as low risk, from 10.3% in to 42.0%. The high NPV (97.2%) in the original group was preserved (97.6%) in the reclassified low risk group, as was the sensitivity (original 99.1% vs. reclassified 96.9%). Conclusion The addition of negative biomarker test results to patients with a moderate risk of appendicitis based on the PAS can safely reclassify many to a low risk group. This may allow clinicians to provide more conservative management in children with suspected appendicitis, and decrease unnecessary resource utilization.
Objective To examine the relation between baseline fat mass and gain in bone area and bone mass in preschoolers studied prospectively for 4 years, with a focus on the role of physical activity and TV ...viewing. Study design Children were part of a longitudinal study in which measures of fat, lean and bone mass, height, weight, activity, and diet were taken every 4 months from ages 3 to 7 years. Activity was measured by accelerometer and TV viewing by parent checklist. We included 214 children with total body dual energy x-ray absorptiometry (Hologic 4500A) scans at ages 3.5 and 7 years. Results Higher baseline fat mass was associated with smaller increases in bone area and bone mass over the next 3.5 years ( P < .001). More TV viewing was related to smaller gains in bone area and bone mass accounting for race, sex, and height. Activity by accelerometer was not associated with bone gains. Conclusions Adiposity and TV viewing are related to less bone accrual in preschoolers.
To assess pretreatment and interventional parameters as predictors of favorable Activity Measure for Post-Acute Care (AM-PAC) scores for optimal discharge planning.
In this prospectively collected, ...retrospectively reviewed multicenter study from 9/1/2017 to 9/22/2022, patients were dichotomized into favorable and unfavorable AM-PAC. Multivariate logistic regression and receiver operator characteristics analyses were performed for the identified significant variables. A
value of ≤.05 was significant.
Hospitalized care.
In total, 229 patients (mean ±SD 70.65 ±15.2 55.9% women) met our inclusion criteria. Inclusion criteria were (a) computed tomography (CT) angiography confirmed LVO from 9/1/2017 to 9/22/2022; (b) diagnostic CT perfusion; and (c) available AM-PAC scores.
None.
Favorable AM-PAC, defined as a daily activity score ≥19 and basic mobility score of ≥17.
Patients with favorable AM-PAC were younger (61.3 vs 70.7,
<.001), had lower admission glucose (mean, 124 vs 136,
=.042), lower blood urea nitrogen (mean, 15.59 vs 19.11,
<.001), and lower admission National Institutes of Health Stroke Scale (NIHSS) (mean, 10.58 vs 16.15,
<.001). No differences in sex were noted. Multivariate regression analyses revealed age, admission NIHSS, relative cerebral blood flow (rCBF) <30% volume, and modified thrombolysis in cerebral infarction (mTICI) score to be independent predictors of favorable AM-PAC (
<.047 for all predictors). The combined model revealed an area under the curve (AUC) of 0.83 (IQR 0.75-0.86).
Excellent recanalization, smaller core volumes, younger age, and lower stroke severity independently predict favorable outcomes as measured by AM-PAC.
Abstract Objectives Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are ...at low risk of acute appendicitis. Methods This study prospectively enrolled subjects > 18 years of age presenting to seven U.S. emergency departments with < 72 hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. Results 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3–99.3%), a negative predictive value of 98.4% (95% CI, 94.4–99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02–0.27), with a specificity of 36.5% (95% CI, 31.6–41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. Conclusion This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis.
Abstract Objectives To prospectively validate the diagnostic accuracy of a biomarker panel consisting of WBC, CRP, and MRP 8/14 levels in identifying pediatric patients with abdominal pain who are at ...low risk of appendicitis. Methods This prospective observational study enrolled subjects aged 2-20 years presenting to 29 U.S. emergency departments with abdominal pain suggesting possible acute appendicitis. Blood samples were analyzed for WBC, CRP, and MRP 8/14 levels from which the composite biomarker panel results were calculated, then correlated with the final diagnosis either positive or negative for acute appendicitis. Results 2201 patients were enrolled, with 1887 completing all aspects of the study. Prevalence of appendicitis in this cohort was 25.3%. The biomarker panel exhibited a sensitivity of 97.1% (95% CI, 95.1-98.2%), negative predictive value of 97.4% (95% CI, 95.8-98.5%), negative likelihood ratio of 0.08 (95% CI, 0.05-0.13), with a specificity of 37.9% (95% CI, 35.4-40.4%) for appendicitis. The panel correctly identified 534 of 1410 (37.8%) patients who did not have appendicitis with 14 (2.9%) false negatives. Overall, 23.7% (132/557) of CT scans were done for patients with negative biomarker panel results, including 31.2% (131/420) of patients who had CT but did not have appendicitis. Conclusion This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this large prospective cohort. This panel may be useful in identifying pediatric patients who are at low risk of appendicitis and might be followed clinically, potentially reducing the dependence on CT in the evaluation for acute appendicitis.
Background Quality of life (QOL) is an important but understudied outcome after lung transplantation. Previous cross-sectional, single-center studies suggest improved QOL, but few prior longitudinal ...multicenter data exist regarding the effect of transplantation on the patient's QOL. Methods We hypothesized that lung transplantation confers a 1-year QOL benefit in both physical and psychologic well-being; we further hypothesized that the magnitude of benefit would vary by sex, native disease, age, or type of transplant operation. To test these hypotheses, we conducted a secondary analysis using QOL data prospectively and serially measured with the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36) in a multicenter cytomegalovirus prevention clinical trial. Linear mixed-effects models were used to assess the impact of transplantation on the recipient's QOL. Results Over the first year after lung transplantation, the SF-36 Physical Component Score significantly increased an average of 10.9 points from baseline levels ( P < .0001). A positive benefit was observed for all native diseases; however, the magnitude varied slightly by native disease ( P = .04) but not by sex ( P = .35), age ( P = .06), or transplant type ( P = .30). In contrast, the SF-36 Mental Component Score did not change from baseline ( P = .36) and remained well below population norms. Conclusions Our results demonstrate that lung transplantation confers clinically important QOL benefits in physical domains but not in psychologic well-being. A better understanding of the barriers to psychologic well-being after transplant is critical to enhancing the benefits of lung transplantation.
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