Search

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

Mutation and recombination are central processes driving microbial evolution. A high mutation rate fuels adaptation but also generates deleterious mutations. Recombination between two different genomes may resolve this paradox, alleviating effects of clonal interference and purging deleterious mutations. Here we demonstrate that recombination significantly accelerates adaptation and evolution during acute virus infection. We identified a poliovirus recombination determinant within the virus polymerase, mutation of which reduces recombination rates without altering replication fidelity. By generating a panel of variants with distinct mutation rates and recombination ability, we demonstrate that recombination is essential to enrich the population in beneficial mutations and purge it from deleterious mutations. The concerted activities of mutation and recombination are key to virus spread and virulence in infected animals. These findings inform a mathematical model to demonstrate that poliovirus adapts most rapidly at an optimal mutation rate determined by the trade-off between selection and accumulation of detrimental mutations.

BackgroundSince 1990, the National Cancer Institute (NCI) and Centers for Medicare and Medicaid Services (CMS) have collaborated to create linked data resources to improve our understanding of patterns of care, health care costs, and trends in utilization. However, existing data linkages have not included measures of patient experiences with care.ObjectiveTo describe a new resource for quality of care research based on a linkage between the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS®) patient surveys and the NCI's Surveillance, Epidemiology and End Results (SEER) data.DesignThis is an observational study of CAHPS respondents and includes both fee-for-service and Medicare Advantage beneficiaries with and without cancer. The data linkage includes: CAHPS survey data collected between 1998 and 2010 to assess patient reports on multiple aspects of their care, such as access to needed and timely care, doctor communication, as well as patients' global ratings of their personal doctor, specialists, overall health care, and their health plan; SEER registry data (1973-2007) on cancer site, stage, treatment, death information, and patient demographics; and longitudinal Medicare claims data (2002-2011) for fee-for-service beneficiaries on utilization and costs of care.ParticipantsIn total, 150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer cohort.Main measuresThe data linkage includes SEER data on cancer site, stage, treatment, death information, and patient demographics, in addition to longitudinal data from Medicare claims and information on patient experiences from CAHPS surveys.Key resultsSizable proportions of cases from common cancers (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g., pancreas) by time since diagnosis enable comparisons across the cancer care trajectory by MA vs. FFS coverage.ConclusionsSEER-CAHPS is a valuable resource for information about Medicare beneficiaries' experiences of care across different diagnoses and treatment modalities, and enables comparisons by type of insurance.

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the need for survey mode adjustments to hospital care evaluations by discharged inpatients and develop the appropriate adjustments. Data Source. A total of 7,555 respondents from a 2006 national random sample of 45 hospitals who completed the CAHPS® Hospital (HCAHPS [Hospital Consumer Assessments of Healthcare Providers and Systems]) Survey. Study Design/Data Collection/Extraction Methods. We estimated mode effects in linear models that predicted each HCAHPS outcome from hospital-fixed effects and patient-mix adjustors. Principal Findings. Patients randomized to the telephone and active interactive voice response (IVR) modes provided more positive evaluations than patients randomized to mail and mixed (mail with telephone follow-up) modes, with some effects equivalent to more than 30 percentile points in hospital rankings. Mode effects are consistent across hospitals and are generally larger than total patient-mix effects. Patient-mix adjustment accounts for any nonresponse bias that could have been addressed through weighting. Conclusions. Valid comparisons of hospital performance require that reported hospital scores be adjusted for survey mode and patient mix. [ABSTRACT FROM AUTHOR]

Objective. To describe the developmental process for the CAHPS® Hospital Survey. Study Design. A pilot was conducted in three states with 19,720 hospital discharges. Methods of Analysis. A rigorous, multi-step process was used to develop the CAHPS Hospital Survey. It included a public call for measures, multiple Federal Register notices soliciting public input, a review of the relevant literature, meetings with hospitals, consumers and survey vendors, cognitive interviews with consumer, a large-scale pilot test in three states and consumer testing and numerous small-scale field tests. Findings. The current version of the CAHPS Hospital Survey has survey items in seven domains, two overall ratings of the hospital and five items used for adjusting for the mix of patients across hospitals and for analytical purposes. Conclusions. The CAHPS Hospital Survey is a core set of questions that can be administered as a stand-alone questionnaire or combined with a broader set of hospital specific items. [ABSTRACT FROM AUTHOR]

The Medicare+Choice (M+C) program, created by the 1997 Balanced Budget Act (BBA), expands Medicare's health insurance options to include a wider range of health plan options. In this article, we describe the Consumer Assessment of Health Plans Study (CAHPS ® ) survey and its use with beneficiaries receiving care through Medicare managed care (MMC) plans. We also discuss the implications of these efforts for future quality improvement efforts.