Background
An objective of the phase 3 HELP Study was to investigate the effect of lanadelumab on health‐related quality of life (HRQoL) in patients with hereditary angioedema (HAE).
Methods
Patients ...with HAE‐1/2 received either lanadelumab 150 mg every 4 weeks (q4wks; n = 28), 300 mg q4wks (n = 29), 300 mg every 2 weeks (q2wks; n = 27), or placebo (n = 41) for 26 weeks (days 0–182). The Angioedema Quality of Life Questionnaire (AE‐QoL) was administered monthly, consisting of four domain (functioning, fatigue/mood, fears/shame, nutrition) and total scores. The generic EQ‐5D‐5L questionnaire was administered on days 0, 98, and 182. Comparisons were made between placebo and (a) all lanadelumab‐treated patients and (b) individual lanadelumab groups for changes in scores (day 0–182) and proportions achieving the minimal clinically important difference (MCID, −6) in AE‐QoL total score.
Results
Compared with the placebo group, the lanadelumab total group demonstrated significantly greater improvements in AE‐QoL total and domain scores (mean change, −13.0 to −29.3; p < 0.05 for all); the largest improvement was in functioning. A significantly greater proportion of the lanadelumab total group achieved the MCID (70% vs 37%; p = 0.001). The lanadelumab 300 mg q2wks group had the highest proportion (81%; p = 0.001) and was 7.2 times more likely to achieve the MCID than the placebo group. Mean EQ‐5D‐5L scores at day 0 were high in all groups, indicating low impairment, with no significant changes at day 182.
Conclusion
Patients with HAE‐1/2 experienced significant and clinically meaningful improvements in HRQoL measured by AE‐QoL following lanadelumab treatment in the HELP Study.
In the phase 3 HELP Study, HRQoL (health‐related quality of life) of patients with HAE (hereditary angioedema)‐1/2 was evaluated using the angioedema‐specific AE‐QoL (Angioedema Quality of Life Questionnaire). After 26 weeks, lanadelumab‐treated patients experienced significantly greater HRQoL improvements than placebo‐treated patients. Patients receiving lanadelumab 300 mg q2wks (every 2 weeks) were most likely to see clinically meaningful benefit, with 81% reaching the MCID (minimal clinically important difference) and seven times greater odds vs placebo for this achievement.
Abbreviations: AE‐QoL, Angioedema Quality of Life Questionnaire; HAE, hereditary angioedema; HRQoL, health‐related quality of life; MCID, minimal clinically important difference; q2wks, every 2 weeks; q4wks, every 4 weeks.
The NuTeV Collaboration has extracted the electroweak parameter sin(2)theta(W) from the measurement of the ratios of neutral current to charged current nu and (-)nu cross sections. Our value, ...sin(2)theta((on-shell))(W) = 0.2277 +/- 0.0013(stat) +/- 0.0009(syst), is 3 standard deviations above the standard model prediction. We also present a model independent analysis of the same data in terms of neutral-current quark couplings.
BACKGROUND:The International Committee of Medical Journal Editors has devised a system of mandatory disclosure, under which authors are required to disclose all conflicts of interest and the sources ...of support for the submitted research. Because payments from industry to physicians generally are common, it is likely that many authors of medical manuscripts will have information to disclose. As a result, the signal-to-noise ratio of such declarations may be low, thereby undermining the effectiveness of disclosure. To our knowledge, the comparative prevalence of such conflicts has not been reported.
METHODS:We identified 100 consecutive scientific articles from the 2014 volumes of 3 journals with high impact factorsPediatrics, The Journal of Bone & Joint Surgery (JBJS), and The New England Journal of Medicine (NEJM). Each study was categorized by funding source and other relationships with industry.
RESULTS:In Pediatrics, 17 of 100 studies had a declared relationship with industry. Industry relationships were declared in 68 and 77 of the studies in JBJS and NEJM, respectively.
CONCLUSIONS:Industry relationships were common in studies in NEJM and JBJS, but rare in Pediatrics. The high prevalence of conflicts of interest may weaken the meaning of declarations and undermine any bias-reducing effect intended by the disclosure system.
The NuMI neutrino beam Adamson, P.; Andrews, R.; Augustine, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2016, Letnik:
806
Journal Article
Recenzirano
Odprti dostop
This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual ...elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.
To examine the effect of autoimmune (AI) disease on the composite outcome of intensive care unit (ICU) admission, intubation, or death from COVID-19 in hospitalized patients.
Retrospective cohort ...study of 186 patients hospitalized with COVID-19 between March 1, 2020, and April 15, 2020 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with AI disease and 124 age- and sex-matched controls. The primary outcome was a composite of ICU admission, intubation, and death, with secondary outcome as time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between AI disease and clinical outcomes.
Patients with AI disease were more likely to have at least one comorbidity (87.1% vs 74.2%,
= 0.04), take chronic immunosuppressive medications (66.1% vs 4.0%,
< 0.01), and have had a solid organ transplant (16.1% vs 1.6%,
< 0.01). There were no significant differences in ICU admission (13.7% vs 19.4%,
= 0.32), intubation (13.7% vs 17.7%,
= 0.47), or death (16.1% vs 14.5%,
= 0.78). On multivariable analysis, patients with AI disease were not at an increased risk for a composite outcome of ICU admission, intubation, or death (OR
0.79, 95% CI 0.37-1.67). On Cox regression, AI disease was not associated with in-hospital mortality (HR
0.73, 95% CI 0.33-1.63).
Among patients hospitalized with COVID-19, individuals with AI disease did not have an increased risk of a composite outcome of ICU admission, intubation, or death.
Charged lepton flavor violation (CLFV) is a clear signal of new physics; it directly addresses the physics of flavor and of generations. The search for CLFV has continued from the early 1940s, when ...the muon was identified as a separate particle, until today. Certainly in the LHC era the motivations for continued searches are clear and have been covered in many reviews. This review is focused on the experimental history with a view toward how these searches might progress. We examine the status of searches for charged lepton flavor violation in the muon, tau, and other channels, and then examine the prospects for new efforts over the next decade. Finally, we examine what paths might be taken after the conclusion of upcoming experiments and what facilities might be required.
This work and its companion paper, Amon et al. Phys. Rev. D 105, 023514 (2022), present cosmic shear measurements and cosmological constraints from over 100 million source galaxies in the Dark Energy ...Survey (DES) Year 3 data. We constrain the lensing amplitude parameter S8≡σ8Ωm/0.3 at the 3% level in ΛCDM: S8=0.759-0.023+0.025 (68% CL). Our constraint is at the 2% level when using angular scale cuts that are optimized for the ΛCDM analysis: S8=0.772-0.017+0.018 (68% CL). With cosmic shear alone, we find no statistically significant constraint on the dark energy equation-of-state parameter at our present statistical power. We carry out our analysis blind, and compare our measurement with constraints from two other contemporary weak lensing experiments: the Kilo-Degree Survey (KiDS) and Hyper-Suprime Camera Subaru Strategic Program (HSC). We additionally quantify the agreement between our data and external constraints from the Cosmic Microwave Background (CMB). Our DES Y3 result under the assumption of ΛCDM is found to be in statistical agreement with Planck 2018, although favors a lower S8 than the CMB-inferred value by 2.3σ (a p-value of 0.02). This paper explores the robustness of these cosmic shear results to modeling of intrinsic alignments, the matter power spectrum and baryonic physics. We additionally explore the statistical preference of our data for intrinsic alignment models of different complexity. The fiducial cosmic shear model is tested using synthetic data, and we report no biases greater than 0.3σ in the plane of S8×Ωm caused by uncertainties in the theoretical models.
OBJECTIVES:
To evaluate the effectiveness of a stepped-wedge randomized trial of Development of Systems and Education for Human Papillomavirus Vaccination (DOSE HPV), a multilevel intervention.
...METHODS:
DOSE HPV is a 7-session program that includes interprofessional provider education, communication training, data feedback, and tailored systems change. Five primary care pediatric and/or family medicine practices completed interventions between 2016 and 2018; all chose to initiate vaccination at ages 9 to 10. We compared vaccination rates in the preintervention, intervention, and postintervention periods among 9- to 17-year-olds using random-effects generalized linear regression models appropriate for stepped-wedge design, accounting for calendar time and clustering of patients by providers and clinic. Outcomes included (1) the likelihood that eligible patients would receive vaccination during clinic visits; (2) the likelihood that adolescents would complete the series by age 13; and (3) the cumulative effect on population-level vaccine initiation and completion rates. Postintervention periods ranged from 6 to 18 months.
RESULTS:
In the intervention and postintervention periods, the adjusted likelihood of vaccination at an eligible visit increased by >10 percentage points for ages 9 to 10 and 11 to 12, and completion of the vaccine series by age 13 increased by 4 percentage points (P < .001 for all comparisons). Population-level vaccine initiation coverage increased from 75% (preintervention) to 84% (intervention) to 90% (postintervention), and completion increased from 60% (preintervention) to 63% (intervention) to 69% (postintervention).
CONCLUSIONS:
Multilevel interventions that include provider education, data feedback, tailored systems changes, and early initiation of the human papillomavirus vaccine series may improve vaccine series initiation and completion beyond the conclusion of the intervention period.
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