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Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.

Highlights • Nigeria’s national survey estimates of DPT3 and MCV1 coverage fluctuate greatly in recent years. • Much of the variation results from differences in surveys weights, not coverage. • Both USAID DHS and UNICEF MICS allow weights to vary from round-to-round. • Nigeria’s National Nutrition & Health Survey weights do not vary much due to post-stratification. • To compare results from surveys proximate in time, use similar strata weights for clarity., National vaccination coverage estimates from household surveys are widely used in monitoring and planning of immunization programs. In Nigeria, survey-reported national coverage estimates have shown large fluctuations in the past few years. In this paper, we examine the impact of state-level survey weighting on Nigeria’s national vaccination coverage estimation. In particular, we focus three vaccination-related outcomes among children aged 12–23 months: the coverage of the third dose of diphtheria, pertussis, and tetanus vaccine (DPT3); the coverage of the first dose of measles-containing vaccine (MCV1); and the availability rate of home-based vaccination record (HBR). We compare the sample selection and weight assignment of three major survey programs in Nigeria, and show that considerable portions of the changes in survey-reported national coverage estimates can be explained by shifts in state-level weights. Our analysis demonstrates the importance of state weighting method in estimating aggregated national coverage figures and provides important context for interpreting changes in coverage estimates between surveys in the future.

SummaryBackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It’s being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.MethodsThis phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422).FindingsBetween March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (InterpretationNDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.FundingNational Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)

PurposeGiven incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants.MethodsUsing publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (≥13%) black and all other (ResultsNearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with ConclusionsNearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.

Smokers with depressive symptoms have more difficulty quitting smoking than the general population of smokers. The present study examines a web-based treatment using acceptance and commitment therapy (ACT) for smokers with depressive symptoms. The study aimed to determine participant receptivity to the intervention and its effects on smoking cessation, acceptance of internal cues, and depressive symptoms.Smokers who had positive screening results for depressive symptoms at baseline (n = 94) were selected from a randomized controlled trial (N = 222) comparing web-based ACT for smoking cessation (WebQuit.org) with Smokefree.gov. Forty-five participants (48%) completed the three-month follow-up.Compared to Smokefree.gov, WebQuit participants spent significantly more time on site (p =.001) and had higher acceptance of physical cravings (p =.033). While not significant, WebQuit participants were more engaged and satisfied with their program and were more accepting of internal cues overall. There was preliminary evidence that WebQuit participants had higher quit rates (20% versus 12%) and lower depressive symptoms at follow-up (45% versus 56%) than those in Smokefree.gov.This was the first study of web-based ACT for smoking cessation among smokers with depressive symptoms, with promising evidence of receptivity, efficacy, impact on a theory-based change process, and possible secondary effects on depression. A fully powered trial of the ACT WebQuit.org intervention specifically for depressed smokers is needed. This was part of a clinical trial registered as NCT#01166334 at www.clinicaltrials.gov .

Currently, there are over 400 smoking cessation smartphone apps available, downloaded an estimated 780,000 times per month. No prior studies have examined how individuals engage with specific features of cessation apps and whether use of these features is associated with quitting.Using data from a pilot trial of a novel smoking cessation app, we examined: (i) the 10 most-used app features, and (ii) prospective associations between feature usage and quitting.Participants (n = 76) were from the experimental arm of a randomized, controlled pilot trial of an app for smoking cessation called "SmartQuit," which includes elements of both Acceptance and Commitment Therapy (ACT) and traditional cognitive behavioral therapy (CBT). Utilization data were automatically tracked during the 8-week treatment phase. Thirty-day point prevalence smoking abstinence was assessed at 60-day follow-up.The most-used features - quit plan, tracking, progress, and sharing - were mostly CBT. Only two of the 10 most-used features were prospectively associated with quitting: viewing the quit plan (p = 0.03) and tracking practice of letting urges pass (p = 0.03). Tracking ACT skill practice was used by fewer participants (n = 43) but was associated with cessation (p = 0.01).In this exploratory analysis without control for multiple comparisons, viewing a quit plan (CBT) as well as tracking practice of letting urges pass (ACT) were both appealing to app users and associated with successful quitting. Aside from these features, there was little overlap between a feature's popularity and its prospective association with quitting. Tests of causal associations between feature usage and smoking cessation are now needed.

Small area estimation (SAE) is an important endeavor in many fields and is used for resource allocation by both public health and government organizations. Often, complex surveys are carried out within areas, in which case it is common for the data to consist only of the response of interest and an associated sampling weight, reflecting the design. While it is appealing to use spatial smoothing models, and many approaches have been suggested for this endeavor, it is rare for spatial models to incorporate the weighting scheme, leaving the analysis potentially subject to bias. To examine the properties of various approaches to estimation we carry out a simulation study, looking at bias due to both non-response and non-random sampling. We also carry out SAE of smoking prevalence in Washington State, at the zip code level, using data from the 2006 Behavioral Risk Factor Surveillance System. The computation times for the methods we compare are short, and all approaches are implemented in R using currently available packages.

Web-based behavioral interventions for substance use are being developed at a rapid pace, yet there is a dearth of information regarding the most effective methods for recruiting participants into web-based intervention trials. In this paper, we describe our successful recruitment of participants into a pilot trial of web-based Acceptance and Commitment Therapy (ACT) for smoking cessation and compare traditional and web-based methods of recruitment in terms of their effects on baseline participant characteristics, association with study retention and treatment outcome, yield, and cost-effectiveness. Over a 10-week period starting June 15, 2010, we recruited 222 smokers for a web-based smoking cessation study using a variety of recruitment methods. The largest portion of randomized participants were recruited through Google AdWords (36%), followed by medical Internet media (23%), standard media (14%), word of mouth (12%), broadcast emails (11%), and social media (6%). Recruitment source was not related to baseline participant characteristics, 3-month data retention, or 30-day point prevalence smoking abstinence at the 3-month outcome assessment. Cost per randomized participant ranged from $5.27/participant for word of mouth to $172.76/participant for social media, with a mean cost of $42.48/participant. Our diversified approach to recruitment, including both traditional and web-based methods, enabled timely enrollment of participants into the study. Because there was no evidence of a substantive difference in baseline characteristics, retention, or outcomes based on recruitment channel, the yield and cost-effectiveness of recruitment methods may be the more critical considerations in developing a feasible recruitment plan for a web-based smoking cessation intervention study.

Background Preoperative simulation warm-up has been shown to improve performance and reduce errors in novice and experienced surgeons, yet existing studies have only investigated conventional laparoscopy. We hypothesized that a brief virtual reality (VR) robotic warm-up would enhance robotic task performance and reduce errors. Study Design In a 2-center randomized trial, 51 residents and experienced minimally invasive surgery faculty in General Surgery, Urology, and Gynecology underwent a validated robotic surgery proficiency curriculum on a VR robotic simulator and on the da Vinci surgical robot (Intuitive Surgical Inc). Once they successfully achieved performance benchmarks, surgeons were randomized to either receive a 3- to 5-minute VR simulator warm-up or read a leisure book for 10 minutes before performing similar and dissimilar (intracorporeal suturing) robotic surgery tasks. The primary outcomes compared were task time, tool path length, economy of motion, technical, and cognitive errors. Results Task time (−29.29 seconds, p = 0.001; 95% CI, −47.03 to −11.56), path length (−79.87 mm; p = 0.014; 95% CI, −144.48 to −15.25), and cognitive errors were reduced in the warm-up group compared with the control group for similar tasks. Global technical errors in intracorporeal suturing (0.32; p = 0.020; 95% CI, 0.06−0.59) were reduced after the dissimilar VR task. When surgeons were stratified by earlier robotic and laparoscopic clinical experience, the more experienced surgeons (n = 17) demonstrated significant improvements from warm-up in task time (−53.5 seconds; p = 0.001; 95% CI, −83.9 to −23.0) and economy of motion (0.63 mm/s; p = 0.007; 95% CI, 0.18–1.09), and improvement in these metrics was not statistically significantly appreciated in the less-experienced cohort (n = 34). Conclusions We observed significant performance improvement and error reduction rates among surgeons of varying experience after VR warm-up for basic robotic surgery tasks. In addition, the VR warm-up reduced errors on a more complex task (robotic suturing), suggesting the generalizability of the warm-up.

Background— Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance as compared with matched controls. Insulin resistance leads to structural abnormalities in the heart, such as increased left atrial size, left ventricular mass, and alterations in transmitral velocity that can precede the diagnosis of HF. It is not known whether insulin resistance precedes the development of HF or whether the relationship between insulin resistance and HF is present among adults with HF caused by nonischemic heart disease. Methods and Results— We examined 4425 participants (60% women) from the Cardiovascular Health Study after excluding those with HF, myocardial infarction, or treated diabetes mellitus at baseline. We used Cox proportional hazards models to estimate the relative risk of incident HF associated with fasting insulin measured at study entry. There were 1216 cases of incident HF (1103 without antecedent myocardial infarction) during a median follow-up of 12 years (maximum, 19 years). Fasting insulin levels were positively associated with the risk of incident HF (hazard ratio, 1.10; 95% confidence interval, 1.05–1.15, per SD change) when adjusted for age, sex, race, field center, physical activity, smoking, alcohol intake, high-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure, and waist circumference. The association between fasting insulin levels and incident HF was similar for HF without antecedent myocardial infarction (hazard ratio, 1.10; 95% confidence interval, 1.05–1.15). Measures of left atrial size, left ventricular mass, and peak A velocity at baseline were associated both with fasting insulin levels and with HF; however, additional statistical adjustment for these parameters did not completely attenuate the insulin-HF estimate (hazard ratio, 1.08; 95% confidence interval, 1.03–1.14 per 1-SD increase in fasting insulin). Conclusions— Fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF in Cardiovascular Health Study participants, including those without an antecedent myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00005133.

BACKGROUND: Epidemiological studies that assess the health effects of long-term exposure to ambient air pollution are used to inform public policy. These studies rely on exposure models that use data collected from pollution monitoring sites to predict exposures at subject locations. Land use regression (LUR) and universal kriging (UK) have been suggested as potential prediction methods. We evaluate these approaches on a dataset including measurements from three seasons in Los Angeles, CA. METHODS: The measurements of gaseous oxides of nitrogen (NOx) used in this study are from a "snapshot" sampling campaign that is part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The measurements in Los Angeles were collected during three two-week periods in the summer, autumn, and winter, each with about 150 sites. The design included clusters of monitors on either side of busy roads to capture near-field gradients of traffic-related pollution. LUR and UK prediction models were created using geographic information system (GIS)-based covariates. Selection of covariates was based on 10-fold cross-validated (CV) R(2) and root mean square error (RMSE). Since UK requires specialized software, a computationally simpler two-step procedure was also employed to approximate fitting the UK model using readily available regression and GIS software. RESULTS: UK models consistently performed as well as or better than the analogous LUR models. The best CV R(2) values for season-specific UK models predicting log(NOx) were 0.75, 0.72, and 0.74 (CV RMSE 0.20, 0.17, and 0.15) for summer, autumn, and winter, respectively. The best CV R(2) values for season-specific LUR models predicting log(NOx) were 0.74, 0.60, and 0.67 (CV RMSE 0.20, 0.20, and 0.17). The two-stage approximation to UK also performed better than LUR and nearly as well as the full UK model with CV R(2) values 0.75, 0.70, and 0.70 (CV RMSE 0.20, 0.17, and 0.17) for summer, autumn, and winter, respectively. CONCLUSION: High quality LUR and UK prediction models for NOx in Los Angeles were developed for the three seasons based on data collected for MESA Air. In our study, UK consistently outperformed LUR. Similarly, the 2-step approach was more effective than the LUR models, with performance equal to or slightly worse than UK.

Many people living in low- and middle-income countries are not covered by civil registration and vital statistics systems. Consequently, a wide variety of other types of data, including many household sample surveys, are used to estimate health and population indicators. In this paper we combine data from sample surveys and demographic surveillance systems to produce small area estimates of child mortality through time. Small area estimates are necessary to understand geographical heterogeneity in health indicators when full-coverage vital statistics are not available. For this endeavor spatio-temporal smoothing is beneficial to alleviate problems of data sparsity. The use of conventional hierarchical models requires careful thought since the survey weights may need to be considered to alleviate bias due to nonrandom sampling and nonresponse. The application that motivated this work is an estimation of child mortality rates in five-year time intervals in regions of Tanzania. Data come from Demographic and Health Surveys conducted over the period 1991-2010 and two demographic surveillance system sites. We derive a variance estimator of under five years child mortality that accounts for the complex survey weighting. For our application, the hierarchical models we consider include random effects for area, time and survey and we compare models using a variety of measures including the conditional predictive ordinate (CPO). The method we propose is implemented via the fast and accurate integrated nested Laplace approximation (INLA)., Comment: Published at http://dx.doi.org/10.1214/15-AOAS872 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

There is a dual need for (1) innovative theory-based smartphone applications for smoking cessation and (2) controlled trials to evaluate their efficacy. Accordingly, this study tested the feasibility, acceptability, preliminary efficacy, and mechanism of behavioral change of an innovative smartphone-delivered acceptance and commitment therapy (ACT) application for smoking cessation vs. an application following US Clinical Practice Guidelines.Adult participants were recruited nationally into the double-blind randomized controlled pilot trial (n=196) that compared smartphone-delivered ACT for smoking cessation application (SmartQuit) with the National Cancer Institute's application for smoking cessation (QuitGuide).We recruited 196 participants in two months. SmartQuit participants opened their application an average of 37.2 times, as compared to 15.2 times for QuitGuide participants (p0001). The overall quit rates were 13% in SmartQuit vs. 8% in QuitGuide (OR=2.7; 95% CI=0.8-10.3). Consistent with ACT's theory of change, among those scoring low (below the median) on acceptance of cravings at baseline (n=88), the quit rates were 15% in SmartQuit vs. 8% in QuitGuide (OR=2.9; 95% CI=0.6-20.7).ACT is feasible to deliver by smartphone application and shows higher engagement and promising quit rates compared to an application that follows US Clinical Practice Guidelines. As results were limited by the pilot design (e.g., small sample), a full-scale efficacy trial is now needed.

No studies to date have examined the effect of counselor techniques on smoking cessation over the course of treatment. To address this gap, we examined the degree to which the use of specific Acceptance and Commitment Therapy (ACT) counseling techniques in a given session predicted smoking cessation reported at the next session. The data came from the ACT arm of a randomized controlled trial of a telephone-delivered smoking cessation intervention. Trained raters coded 139 counseling sessions across 44 participants. The openness, awareness and activation components of the ACT model were rated for each telephone counseling session. Multilevel logistic regression models were used to estimate the predictive relationship between each component during any given telephone session and smoking cessation at the following telephone session. For every 1-unit increase in counselors' use of openness and awareness techniques there were 42% and 52% decreases in the odds of smoking at the next counseling session, respectively. However, there was no significant predictive relationship between counselors' use of activation techniques and smoking cessation. Overall, results highlight the theoretical and clinical value of examining therapists' techniques as predictors of outcome during the course of treatment.

BACKGROUND Controversies exist in the adult literature regarding the use of kidneys from small donors into larger recipients. Little is known regarding this issue in pediatric kidney transplantation. To assess the impact of donor/recipient size mismatch on long-term renal graft survival in pediatric patients undergoing living-donor renal transplantation. METHODS We reviewed the United Network for Organ Sharing database from 1987 to 2010 for adolescent (11-18 years old) patients who underwent primary living-donor renal transplantation. According to donor/recipient body surface area (BSA) ratio, patients were stratified into two categories: BSA ratio

Surgical infants requiring long-term parenteral nutrition (PN) are at risk for parenteral nutrition-associated liver disease (PNALD). The purpose of this study was to determine the effect of a lipid restricted PN regimen in preventing the development of PNALD in surgical infants.In 2009, we implemented a lipid restricted strategy in surgical infants expected to be on long-term PN using a soy-based lipid emulsion at a goal provision of 1g/kg/day throughout a patient's entire PN course. An experimental cohort of surgical infants treated with lipid restriction from 2009 to 2011 (n=82) was retrospectively compared to a control cohort of infants from 2005 to 2008 receiving standard intravenous lipid dosing (n=132). A multivariable relative risk regression model was constructed analyzing the association between lipid restriction and PNALD.Patients admitted during the lipid restriction era had reduced daily lipid provisions compared to the control group (p0.001). There were no significant differences in demographic or measured clinical characteristics between the two groups. A significant reduction in the incidence of PNALD was demonstrated in the lipid restricted group compared to the control group (22% vs. 43%, p=0.002). On multivariable relative risk regression, patients treated with standard lipid provisions were 1.77 times more likely to develop PNALD than patients who were lipid restricted (95% CI: 1.2-2.7; p=0.007).Restriction of intravenous soy-based lipid in PN-fed surgical infants is associated with a reduction in the incidence of liver disease. Early lipid restriction should be considered in all surgical infants who require PN as a preventative measure against PNALD.