Comparing statistical methods for detecting and estimating waning efficacy of rotavirus vaccines in developing countries.

Introduction: Vaccination has significantly reduced morbidity and mortality resulting from rotavirus infection worldwide. However, rotavirus vaccine efficacy (VE) appears to wane over the first 2 years since vaccination, particularly in developing countries. Statistical methods for detecting VE waning and estimating its rate have been used in a few studies, but comparisons of methods for evaluating VE waning have not yet been performed.

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

Background: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs.

Methods: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures.

Postvaccination Serum Antirotavirus Immunoglobulin A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings.

Background: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis.

Methods: Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 clinical trials from 16 countries were pooled.

Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries.

Background: Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course.

Challenges in estimating influenza vaccine effectiveness.

: Influenza vaccination is regarded as the most effective way to prevent influenza infection. Due to the rapid genetic changes that influenza viruses undergo, seasonal influenza vaccines must be reformulated and re-administered annually necessitating the evaluation of influenza vaccine effectiveness (VE) each year. The estimation of influenza VE presents numerous challenges.

Effect of propensity of seeking medical care on the bias of the estimated effectiveness of rotavirus vaccines from studies using a test-negative case-control design.

Background: Rotavirus is the leading cause of severe diarrhea among children worldwide, and vaccines can reduce morbidity and mortality by 50-98%. The test-negative control (TNC) study design is increasingly used for evaluating the effectiveness of vaccines against rotavirus and other vaccine-preventable diseases. In this study design, symptomatic patients who seek medical care are tested for the pathogen of interest.

Bias of influenza vaccine effectiveness estimates from test-negative studies conducted during an influenza pandemic.

Test-negative (TN) studies have become the most widely used study design for the estimation of influenza vaccine effectiveness (VE) and are easily incorporated into existing influenza surveillance networks. We seek to determine the bias of TN-based VE estimates during a pandemic using a dynamic probability model. The model is used to evaluate and compare the bias of VE estimates under various sources of bias when vaccination occurs after the beginning of an outbreak, such as during a pandemic.

A Dynamic Model for Evaluation of the Bias of Influenza Vaccine Effectiveness Estimates From Observational Studies.

Given that influenza vaccination is now widely recommended in the United States, observational studies based on patients with acute respiratory illness (ARI) remain as the only option to estimate influenza vaccine effectiveness (VE). We developed a dynamic probability model to evaluate bias of VE estimates from passive surveillance cohort, test-negative, and traditional case-control studies. The model includes 2 covariates (health status and health awareness) that might affect the probabilities of vaccination, developing ARI, and seeking medical care.

Longer-term Direct and Indirect Effects of Infant Rotavirus Vaccination Across All Ages in the United States in 2000-2013: Analysis of a Large Hospital Discharge Data Set.

Background: Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated.

Methods: Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras.

A comparison of the test-negative and traditional case-control study designs with respect to the bias of estimates of rotavirus vaccine effectiveness.

Estimation of the effectiveness of rotavirus vaccines via the test-negative control study design has gained popularity over the past few years. In this study design, children with severe diarrhea who test positive for rotavirus infection are considered as cases, while children who test negative serve as controls. We use a simple probability model to evaluate and compare the test-negative control and the traditional case-control designs with respect to the bias of resulting estimates of rotavirus vaccine effectiveness (VE).

A comparison of the test-negative and the traditional case-control study designs for estimation of influenza vaccine effectiveness under nonrandom vaccination.

Background: As annual influenza vaccination is recommended for all U.S. persons aged 6 months or older, it is unethical to conduct randomized clinical trials to estimate influenza vaccine effectiveness (VE).

Maximum likelihood estimation of influenza vaccine effectiveness against transmission from the household and from the community.

Influenza vaccination is recommended as the best way to protect against influenza infection and illness. Due to seasonal changes in influenza virus types and subtypes, a new vaccine must be produced, and vaccine effectiveness (VE) must be estimated, annually. Since 2010, influenza vaccination has been recommended universally in the United States, making randomized clinical trials unethical.

On the bias of estimates of influenza vaccine effectiveness from test-negative studies.

Estimates of the effectiveness of influenza vaccines are commonly obtained from a test-negative design (TND) study, where cases and controls are patients seeking care for an acute respiratory illness who test positive and negative, respectively, for influenza infection. Vaccine effectiveness (VE) estimates from TND studies are usually interpreted as vaccine effectiveness against medically-attended influenza (MAI). However, it is also important to estimate VE against any influenza illness (symptomatic influenza (SI)) as individuals with SI are still a public health burden even if they do not seek medical care.

Estimating Direct and Indirect Protective Effect of Influenza Vaccination in the United States.

With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States.

The case test-negative design for studies of the effectiveness of influenza vaccine in inpatient settings.

Background: The test-negative design (TND) to evaluate influenza vaccine effectiveness is based on patients seeking care for acute respiratory infection, with those who test positive for influenza as cases and the test-negatives serving as controls. This design has not been validated for the inpatient setting where selection bias might be different from an outpatient setting.

Methods: We derived mathematical expressions for vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations and used numerical simulations to verify theoretical results exploring expected biases under various scenarios.

A simulation study of nonparametric total deviation index as a measure of agreement based on quantile regression.

Total deviation index (TDI) captures a prespecified quantile of the absolute deviation of paired observations from raters, observers, methods, assays, instruments, etc. We compare the performance of TDI using nonparametric quantile regression to the TDI assuming normality (Lin, 2000). This simulation study considers three distributions: normal, Poisson, and uniform at quantile levels of 0.

Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

Background: In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1.

Methods: We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014.

The E3 ubiquitin ligase parkin is recruited to the 26 S proteasome via the proteasomal ubiquitin receptor Rpn13.

Mutations in the Park2 gene, encoding the RING-HECT hybrid E3 ubiquitin ligase parkin, are responsible for a common familial form of Parkinson disease. By mono- and polyubiquitinating target proteins, parkin regulates various cellular processes, including degradation of proteins within the 26 S proteasome, a large multimeric degradation machine. In our attempt to further elucidate the function of parkin, we have identified the proteasomal ubiquitin receptor Rpn13/ADRM1 as a parkin-interacting protein.

Effect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: a time series analysis.

Background: In March 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced the seven-valent vaccine in the USA. We assessed the effect of PCV13 use on pneumococcus-related admissions to hospital 2 years after the vaccine was introduced, when coverage in children younger than age 5 years had reached 54%.

Methods: We used data from a private inpatient discharge record database.

Accounting for unintended binding events in the analysis of quartz crystal microbalance kinetic data.

Previous methods for analyzing protein-ligand binding events using the quartz crystal microbalance with dissipation monitoring (QCM-D) fail to account for unintended binding that inevitably occurs during surface measurements and obscure kinetic information. In this article, we present a system of differential equations that accounts for both reversible and irreversible unintended interactions. This model is tested on three protein-ligand systems, each of which has different features, to establish the feasibility of using the QCM-D for protein binding analysis.

Influence of histologic criteria and confounding factors in staging equivocal cases for microscopic perivesical tissue invasion (pT3a): an interobserver study among genitourinary pathologists.

Current oncology guidelines and clinical trials consider giving adjuvant chemotherapy to bladder cancer patients with at least microscopic perivesical tissue invasion (MPVTI) (≥pT3a) on cystectomy. The boundary of muscularis propria (MP) and perivesical tissue is commonly ill defined, and hence, when the tumor involves the interface, interpretation of MPVTI is likely to be subjective. In this study, 20 sets of static images that included 1 nontumoral bladder wall for defining MP-perivesical tissue boundary and 19 bladder cancer cases equivocal for MPVTI with confounding factors were sent to 17 expert genitourinary pathologists for review.

Assessing agreement of repeated binary measurements with an application to the CDC's anthrax vaccine clinical trial.

Cohen's kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. However, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. This study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions and discusses under which condition we should use the most appropriate method in practice.

Comorbid posttraumatic stress disorder and opiate addiction: a literature review.

Treatment of comorbid posttraumatic stress disorder (PTSD) and opioid dependence has been a challenge for many clinicians. There are limited evidence-based guidelines for treatment of this comorbidity. Symptoms of PTSD and opiate dependence may converge, and it is sometimes difficult to differentiate between both conditions.

Inactivated influenza vaccines for prevention of community-acquired pneumonia: the limits of using nonspecific outcomes in vaccine effectiveness studies.

Background: One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP.

Methods: We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models.

Intussusception after rotavirus vaccines reported to US VAERS, 2006-2012.

Background: In 2006 and 2008, 2 new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States.

Methods: We assessed intussusception events reported to the Vaccine Adverse Event Reporting System from February 2006 through April 2012 for RV5 and from April 2008 through April 2012 for RV1. For RV5, we conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception comparing average daily reports 3 to 6 versus 0 to 2 days after vaccination.