Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort

Communications Biophysics

Contains reports on nine research projects split into four sections.National Institutes of Health (Grant 5 PO1 NS13126)National Institutes of Health (Grant 5 KO4 NS00113)National Institutes of Health (Training Grant 5 T32 NS07047)National Institutes of Health (Training Grant 1 T32 NS07099)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 ROI NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 RO1 NS14092)Edith E. Sturgis FoundationHealth Sciences FundNational Institutes of Health (Grant 2 R01 NS11680)National Institutes of Health (Fellowship 5 F32 NS05327)National Institutes of Health (Grant 2 ROI NS11080)National Institutes of Health (Training Grant 5 T32 GM07301

Communications Biophysics

Contains reports on nine research projects split into four sections.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 5 K04 NS00113)National Institutes of Health (Training Grant 5 T32 NS07047)National Institutes of Health (Grant 5 ROl NS11153-03)National Institutes of Health (Fellowship 1 T32 NS07099-01)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 ROl NS10916)National Institutes of Health (Grant 5 ROl NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 RO1 NS14092)Health Sciences FundNational Institutes of Health (Grant 2 R01 NS11680)National Institutes of Health (Grant 2 RO1 NS11080)National Institutes of Health (Training Grant 5 T32 GM07301

Profiling quality of care: Is there a role for peer review?

BACKGROUND: We sought to develop a more reliable structured implicit chart review instrument for use in assessing the quality of care for chronic disease and to examine if ratings are more reliable for conditions in which the evidence base for practice is more developed. METHODS: We conducted a reliability study in a cohort with patient records including both outpatient and inpatient care as the objects of measurement. We developed a structured implicit review instrument to assess the quality of care over one year of treatment. 12 reviewers conducted a total of 496 reviews of 70 patient records selected from 26 VA clinical sites in two regions of the country. Each patient had between one and four conditions specified as having a highly developed evidence base (diabetes and hypertension) or a less developed evidence base (chronic obstructive pulmonary disease or a collection of acute conditions). Multilevel analysis that accounts for the nested and cross-classified structure of the data was used to estimate the signal and noise components of the measurement of quality and the reliability of implicit review. RESULTS: For COPD and a collection of acute conditions the reliability of a single physician review was quite low (intra-class correlation = 0.16–0.26) but comparable to most previously published estimates for the use of this method in inpatient settings. However, for diabetes and hypertension the reliability is significantly higher at 0.46. The higher reliability is a result of the reviewers collectively being able to distinguish more differences in the quality of care between patients (p < 0.007) and not due to less random noise or individual reviewer bias in the measurement. For these conditions the level of true quality (i.e. the rating of quality of care that would result from the full population of physician reviewers reviewing a record) varied from poor to good across patients. CONCLUSIONS: For conditions with a well-developed quality of care evidence base, such as hypertension and diabetes, a single structured implicit review to assess the quality of care over a period of time is moderately reliable. This method could be a reasonable complement or alternative to explicit indicator approaches for assessing and comparing quality of care. Structured implicit review, like explicit quality measures, must be used more cautiously for illnesses for which the evidence base is less well developed, such as COPD and acute, short-course illnesses

CMV Infection Attenuates the Disease Course in a Murine Model of Multiple Sclerosis

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies

Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer

Polymorphisms in the cytochrome P450 1B1 (CYP1B1) and glutathione S-transferase (GST) drug metabolic enzymes, which are responsible for metabolic activation/detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one CYP1B1 119S allele (OR=0.53; 95% CI=0.20–1.40) and increased risk for those women harboring at least one CYP1B1 432V allele (OR=5.52; 95% CI=0.50–61.37). Stratified analyses demonstrated significant interactions in younger (age ≤60) Caucasian women with the CYP1B1 119SS genotype (OR=3.09; 95% CI=1.22–7.84) and younger African-American women with the GSTT1 null genotype (OR=4.07; 95% CI=1.12–14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at GSTP1 114 (OR=2.12; 95% CI=1.02–4.41). In Caucasian women, the combined GSTP1 105IV/VV and CYP1B1 119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04–3.72) and the three way combination of GSTP1 105IV/VV, CYP1B1 119AS/SS and GSTT1 null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27–12.40). These results suggest the importance of estrogen/carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Illusory Stimuli Can Be Used to Identify Retinal Blind Spots

Background. Identification of visual field loss in people with retinal disease is not straightforward as people with eye disease are frequently unaware of substantial deficits in their visual field, as a consequence of perceptual completion ("filling-in'') of affected areas. Methodology. We attempted to induce a compelling visual illusion known as the induced twinkle after-effect (TwAE) in eight patients with retinal scotomas. Half of these patients experience filling-in of their scotomas such that they are unaware of the presence of their scotoma, and conventional campimetric techniques can not be used to identify their vision loss. The region of the TwAE was compared to microperimetry maps of the retinal lesion. Principal Findings. Six of our eight participants experienced the TwAE. This effect occurred in three of the four people who filled-in their scotoma. The boundary of the TwAE showed good agreement with the boundary of lesion, as determined by microperimetry. Conclusion. For the first time, we have determined vision loss by asking patients to report the presence of an illusory percept in blind areas, rather than the absence of a real stimulus. This illusory technique is quick, accurate and not subject to the effects of filling-in