Current strategies to understand the molecular basis of Marek\'s disease virus (MDV) virulence primarily consist of cataloging divergent nucleotides between strains with different phenotypes. However, most comparative genomic studies of MDV rely on previously published consensus genomes despite the confirmed existence of MDV strains as mixed viral populations. To assess the reliability of interstrain genomic comparisons relying on published consensus genomes of MDV, we obtained two additional consensus genomes of vaccine strain CVI988 (Rispens) and two additional consensus genomes of the very virulent strain Md5 by sequencing viral stocks and cultured field isolates. In conjunction with the published genomes of CVI988 and Md5, this allowed us to perform three-way comparisons between multiple consensus genomes of the same strain. We found that consensus genomes of CVI988 can vary in as many as 236 positions involving 13 open reading frames (ORFs). By contrast, we found that Md5 genomes varied only in 11 positions involving a single ORF. Notably, we were able to identify 3 single-nucleotide polymorphisms (SNPs) in the unique long region and 16 SNPs in the unique short (US) region of CVI988GenBank.BAC that were not present in either CVI988Pirbright.lab or CVI988USDA.PA.field. Recombination analyses of field strains previously described as natural recombinants of CVI988 yielded no evidence of crossover events in the US region when either CVI988Pirbright.lab or CVI988USDA.PA.field were used to represent CVI988 instead of CVI988GenBank.BAC. We were also able to confirm that both CVI988 and Md5 populations were mixed, exhibiting a total of 29 and 27 high-confidence minor variant positions, respectively. However, we did not find any evidence of minor variants in the positions corresponding to the 19 SNPs in the unique regions of CVI988GenBank.BAC. Taken together, our findings suggest that continued reliance on the same published consensus genome of CVI988 may have led to an overestimation of genomic divergence between CVI988 and virulent strains and that multiple consensus genomes per strain may be necessary to ensure the accuracy of interstrain genomic comparisons.

The United States Preventive Services Task Force recommends that medical providers apply fluoride varnish (FV) to the teeth of all children under 6 years of age, but fewer than 10% of eligible children receive FV as recommended. Prior studies suggest that variation in clinical guidelines is associated with low uptake of other evidence-based health-related interventions, but consistency of national guidelines for the delivery of FV in medical settings is unknown.
Eligible guidelines for application of FV in medical settings for children under 6 years of age were published in the past 10 years by national pediatric or dental professional organizations or by national public health entities. Guidelines were identified using the search terms fluoride varnish + [application; guidelines, or recommendations; children or pediatric; American Academy of Pediatrics (AAP); American Academy of Pediatric Dentistry] and a search of Guideline Central. Details of the guidelines were extracted and compared.
Ten guidelines met inclusion criteria. Guidelines differed in terms of periodicity recommendations and whether FV was indicated for children with a dental home or level of risk of dental caries.
Numerous recommendations about FV delivery in medical settings are available to pediatric medical providers. Further study is warranted to determine whether the variation across current guidelines detected in this study may contribute to low FV application rates in medical settings.

According to (inter-)national guidelines, (neo-)adjuvant and concurrent androgen deprivation therapy (ADT) in combination with external beam radiotherapy (EBRT) is optional for intermediate-risk prostate cancer (PCa) patients and is the recommended standard treatment for high-risk PCa patients.
The aim of this study is to provide insight into the prescription of ADT in intermediate- and high-risk PCa patients treated with EBRT in the Netherlands, and to evaluate adherence to European Association of Urology guidelines and factors affecting prescription.
All intermediate- and high-risk PCa patients between October 2015 and April 2016 were identified through the population-based Netherlands Cancer Registry. Variation in the prescription of ADT in patients with EBRT was evaluated. Multivariable multilevel logistic regression analyses were performed to determine the probability of ADT and to examine the role of patient-, tumour-, and hospital-related factors.
Overall, 29% of patients with intermediate-risk PCa received ADT varying from 3% to 73% between institutions. From the multivariable regression analysis, higher Gleason grade, magnetic resonance imaging, and computed tomography (CT)-positron-emission tomography/CT prior to radiotherapy appeared to be associated with increased prescription of ADT. Among high-risk patients, 83% received ADT, varying from 57% to 100% between departments. A higher prostate-specific antigen level, more advanced tumour stage, and a higher Gleason grade were associated with increased prescription.
Less than one-third of intermediate-risk PCa patients treated with EBRT receive ADT. The variation in the prescription of ADT between different institutions is substantial. This suggests that the prescription is largely dependent on different institutional policies. The guideline adherence in high-risk PCa is fairly good, as the vast majority of patients received ADT as recommended. However, given the clear recommendations in the guidelines, adherence could be improved.
In this review, we looked at the variation of hormonal treatment in intermediate- and high-risk prostate cancer patients. We found substantial variation between institutions.

Recent methodological advances in both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have facilitated the profiling highly complex mixtures of primary and secondary metabolites in order to investigate a diverse range of biological questions. These techniques usually face a large number of potential sources of technical and biological variation. In this chapter we describe guidelines and normalization procedures to reduce the analytical variation, which are essential for the high-throughput evaluation of metabolic variance used in broad genetic populations which commonly entail the evaluation of hundreds or thousands of samples. This chapter specifically deals with handling of large-scale plant samples for metabolomics analysis of quantitative trait loci (mQTL) in order to reduce analytical error as well as batch-to-batch variation.

BACKGROUND: We explored regional variation in 30-day ischemic stroke mortality and readmission rates and the extent to which regional differences in patients, hospitals, healthcare resources, and a quality of care composite care measure explain the observed variation.
RESULTS: This ecological analysis aggregated patient and hospital characteristics from the Get With The Guidelines-Stroke registry (2007-2011), healthcare resource data from the Dartmouth Atlas of Health Care (2006), and Medicare fee-for-service data on 30-day mortality and readmissions (2007-2011) to the hospital referral region (HRR) level. We used linear regression to estimate adjusted HRR-level 30-day outcomes, to identify HRR-level characteristics associated with 30-day outcomes, and to describe which characteristics explained variation in 30-day outcomes. The mean adjusted HRR-level 30-day mortality and readmission rates were 10.3% (SD=1.1%) and 13.1% (SD=1.1%), respectively; a modest, negative correlation (r=-0.17; P=0.003) was found between one another. Demographics explained more variation in readmissions than mortality (25% versus 6%), but after accounting for demographics, comorbidities accounted for more variation in mortality compared with readmission rates (17% versus 7%). The combination of hospital characteristics and healthcare resources explained 11% and 16% of the variance in mortality and readmission rates, beyond patient characteristics. Most of the regional variation in mortality (65%) and readmission (50%) rates remained unexplained.
CONCLUSIONS: Thirty-day mortality and readmission rates vary substantially across HRRs and exhibit an inverse relationship. While regional variation in 30-day outcomes were explained by patient and hospital factors differently, much of the regional variation in both outcomes remains unexplained.

BACKGROUND: Evidence indicates that early detection and management of dementia care can improve outcomes. We assess variations in dementia care based on processes outlined in clinical guidelines by the BC Ministry of Health.
METHODS: A population-based retrospective cohort study of community-dwelling seniors using patient-level administrative data in British Columbia, Canada. Guidelines measured: laboratory testing, imaging, prescriptions, complete examination, counseling, and specialist referral.
RESULTS: Older patients were less likely to receive guideline-consistent medical care. Patients in higher income categories had higher odds of receiving counseling (confidence interval or CI 1.13-153) and referrals (15.1 CI 1.18-1.95) compared with those of lower income. Over a quarter of the cohort received an antipsychotic (28%) or nonrecommended benzodiazepine (26%). Individuals living within \"rural\" health authorities or of low income were more likely to receive antipsychotic treatment.
CONCLUSIONS: Patterns of inequality by age and income may signal barriers to care, particularly for management of dementia care processes.

BACKGROUND: Clinical practice guidelines (cpgs) are systematically developed statements designed to assist practitioners and patients in making decisions about appropriate heath care interventions. Clinical practice guidelines are expensive and time-consuming to create. A cpg on concurrent chemotherapy with radiation therapy (ccrt) was developed in Ontario at a time when treatment approaches for head-and-neck cancer were changing significantly.
METHODS: An assessment of treatments and outcomes based on electronic and chart data obtained from a population-based study of 571 patients with oropharynx cancer treated in Ontario (2003-2004) was combined with a review of relevant knowledge transfer (publications and presentations at major meetings) to understand variation in adherence to a cpg.
RESULTS: In 9 Ontario cancer treatment centres, ccrt was used for 55% of all patients with oropharyngeal cancer; however, at the centres individually, that proportion ranged from 82% to 39%. Furthermore, there was no agreement on the chemotherapy regimen: 2-4 years later (a period during which newer regimens were emerging), only 4 of 9 centres were following the guideline for most patients. When outcomes of treated patients were compared for centres with \"higher\" and \"lower\" use of ccrt, no difference in survival was observed (p = 0.64).
CONCLUSIONS: At a time of treatment evolution, the new guideline was controversial, and there are many reasons for the mixed adherence. An estimation of adherence should be included during both development and review of guidelines.

Modelling demand for radiotherapy is contingent on the uniform application of clinical practice guidelines. However, decision making in lung cancer is a complex process requiring the integration of multimodality treatment in patients who frequently have underlying comorbidities. Population studies have shown that guideline adherence in lung cancer is modest, ranging from 44 to 52%. The application of guideline treatment decreases with increasing age and the presence of comorbidities. Patient and clinician attitudes also impact on this. In some regions, sociodemographic factors, such as lower income and non-White race, have been associated with a lack of guideline treatment. One of the major barriers in treating lung cancer patients according to guidelines is the mismatch between the clinic population and those enrolled in clinical trials from which evidence is derived. The lung cancer clinic population often consists of patients who are older, have multiple comorbidities and are of borderline performance status, all characteristics that are usually exclusion criteria for clinical trials. Hence, there is uncertainty not only about the magnitude of benefit, but also potential toxicities of guideline treatment. Further research is necessary in order to define the best treatment in these patients and thus increase the applicability of guidelines to the general lung cancer population. Lung cancer is an extreme example of the difficulties in translating evidence into clinical practice. The applicability of guidelines to specific cancer populations will affect the modelling of demand for radiotherapy and other treatment modalities.