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Background: Clinical adoption of the sequencing of circulating tumor DNA (ctDNA) for cancer has rapidly increased in recent years. This sequencing is used to select targeted therapy and monitor nonresponding or progressive tumors to identify mechanisms of therapeutic resistance. Our study objective was to review available coverage policies for cancer ctDNA–based testing panels to examine trends from 2015 to 2019. Methods: We analyzed publicly available private payer policies and Medicare national coverage determinations and local coverage determinations (LCDs) for ctDNA-based panel tests for cancer. We coded variables for each year representing policy existence, covered clinical scenario, and specific ctDNA test covered. Descriptive analyses were performed. Results: We found that 38% of private payer coverage policies provided coverage of ctDNA-based panel testing as of July 2019. Most private payer policy coverage was highly specific: 87% for non–small cell lung cancer, 47% for EGFR gene testing, and 79% for specific brand-name tests. There were 8 final, 2 draft, and 2 future effective final LCDs (February 3 and March 15, 2020) that covered non–FDA-approved ctDNA-based tests. The draft and future effective LCDs were the first policies to cover pan-cancer use. Conclusions: Coverage of ctDNA-based panel testing for cancer indications increased from 2015 to 2019. The trend in private payer and Medicare coverage is an increasing number of coverage policies, number of positive policies, and scope of coverage. We found that Medicare coverage policies are evolving to pan-cancer uses, signifying a significant shift in coverage frameworks. Given that genomic medicine is rapidly changing, payers and policymakers (eg, guideline developers) will need to continue to evolve policies to keep pace with emerging science and standards in clinical care.

BackgroundA key tenet of sports performance research is to provide coaches and athletes with information to inform better practice, yet the determinants of athletic performance in actual competition remain an under-examined and under-theorised field. In cycling, the effects of contextual factors, presence of and interaction with opponents, environmental conditions, competition structure and socio-cultural, economic and authoritarian mechanisms on the performance of cyclists are not well understood.ObjectivesTo synthesise published findings on the determinants of cyclists’ behaviours and chances of success in elite competition.MethodsFour academic databases were searched for peer-reviewed articles. A total of 44 original research articles and 12 reviews met the inclusion criteria. Key findings were grouped and used to shape a conceptual framework of the determinants of performance.ResultsThe determinants of cycling performance were grouped into four dimensions: features related to the individual cyclist, tactical features emerging from the inter-personal dynamics between cyclists, strategic features related to competition format and the race environment and global features related to societal and organisational constraints. Interactions between these features were also found to shape cyclists’ behaviours and chances of success.ConclusionTeam managers, coaches, and athletes seeking to improve performance should give attention to features related not only to the individual performer, but also to features of the interpersonal, strategic, global dimensions and their interactions.

Objectives:The objective of this article is to describe the unique challenges and present potential solutions and approaches for economic evaluations of precision medicine (PM) interventions using simulation modeling methods. Methods:Given the large and growing number of PM interventions and applications, methods are needed for economic evaluation of PM that can handle the complexity of cascading decisions and patient-specific heterogeneity reflected in the myriad testing and treatment pathways. Traditional approaches (eg, Markov models) have limitations, and other modeling techniques may be required to overcome these challenges. Dynamic simulation models, such as discrete event simulation and agent-based models, are used to design and develop mathematical representations of complex systems and intervention scenarios to evaluate the consequence of interventions over time from a systems perspective. Results:Some of the methodological challenges of modeling PM can be addressed using dynamic simulation models. For example, issues regarding companion diagnostics, combining and sequencing of tests, and diagnostic performance of tests can be addressed by capturing patient-specific pathways in the context of care delivery. Issues regarding patient heterogeneity can be addressed by using patient-level simulation models. Conclusion:The economic evaluation of PM interventions poses unique methodological challenges that might require new solutions. Simulation models are well suited for economic evaluation in PM because they enable patient-level analyses and can capture the dynamics of interventions in complex systems specific to the context of healthcare service delivery.

Objectives Given the potential of real-world evidence (RWE) to inform understanding of the risk–benefit profile of next-generation sequencing (NGS)–based testing, we undertook a study to describe the current landscape of whether and how payers use RWE as part of their coverage decision making and potential solutions for overcoming barriers. Methods We performed a scoping literature review of existing RWE evidentiary frameworks for evaluating new technologies and identified barriers to clinical integration and evidence gaps for NGS. We synthesized findings as potential solutions for improving the relevance and utility of RWE for payer decision-making. Results Payers require evidence of clinical utility to inform coverage decisions, yet we found a relatively small number of published RWE studies, and these are predominately focused on oncology, pharmacogenomics, and perinatal/pediatric testing. We identified 3 categories of innovation that may help address the current undersupply of RWE studies for NGS: (1) increasing use of RWE to inform outcomes-based contracting for new technologies, (2) precision medicine initiatives that integrate clinical and genomic data and enable data sharing, and (3) Food and Drug Administration reforms to encourage the use of RWE. Potential solutions include development of data and evidence review standards, payer engagement in RWE study design, use of incentives and partnerships to lower the barriers to RWE generation, education of payers and providers concerning the use of RWE and NGS, and frameworks for conducting outcomes-based contracting for NGS. Conclusions We provide numerous suggestions to overcome the data, methodologic, infrastructure, and policy challenges constraining greater integration of RWE in assessments of NGS.

PurposeExome sequencing (ES) has the potential to improve management of congenital anomalies and neurodevelopmental disorders in fetuses, infants, and children. US payers are key stakeholders in patient access to ES. We examined how payers view insurance coverage and clinical utility of pediatric and prenatal ES.MethodsWe employed the framework approach of qualitative research to conduct this study. The study cohort represented 14 payers collectively covering 170,000,000 enrollees.ResultsSeventy-one percent of payers covered pediatric ES despite perceived insufficient evidence because they saw merit in available interventions or in ending the diagnostic odyssey. None covered prenatal ES, because they saw no merit. For pediatric ES, 50% agreed with expanded aspects of clinical utility (e.g., information utility), and 21% considered them sufficient for coverage. For prenatal ES, payers saw little utility until in utero interventions become available.ConclusionThe perceived merit of ES is becoming a factor in payers' coverage for serious diseases with available interventions, even when evidence is perceived insufficient. Payers' views on ES's clinical utility are expanding to include informational utility, aligning with the views of patients and other stakeholders. Our findings inform clinical research, patient advocacy, and policy-making, allowing them to be more relevant to payers.

Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.

Background Early and accurate detection of stress remodelling in racehorses is of utmost importance to prevent catastrophic injuries. Current imaging techniques have limitations in assessing early changes predisposing to catastrophic breakdowns. Positron emission tomography (PET) using 18 F-sodium fluoride (18 F-NaF) is a sensitive method for the detection of early bone turnover and may improve early recognition of subtle injuries. Objectives To validate the clinical use of 18 F-NaF PET in Thoroughbred racehorses, to assess the value of PET in the detection of bone lesions and to compare PET results with findings of other advanced imaging modalities, clinical examination and pathology. Study design Experimental exploratory study. Methods Twenty fetlocks from nine Thoroughbred racehorses were imaged using 18 F-NaF PET, computed tomography (CT) and scintigraphy. Five fetlocks were also imaged with magnetic resonance imaging and four fetlocks were also examined histologically. Imaging findings were independently reviewed by three board certified radiologists. Imaging, clinical and histopathological findings were correlated. Results PET imaging was well-tolerated by all horses. PET detected focal areas of 18 F-NaF uptake in instances where other imaging modalities did not identify abnormalities, in particular in the proximal sesamoid bones. Maximal standardised uptake values could be measured to quantify the activity of lesions. Areas of 18 F-NaF uptake corresponded to regions of increased vascularity and increased osteoblastic activity. Main limitations Limited number of cases. Conclusions 18 F-NaF PET imaging of the Thoroughbred fetlock is feasible and compares favourably with other imaging modalities in detecting stress remodelling in Thoroughbred racehorses. PET appears to be a beneficial imaging modality when used for early detection of stress remodelling in an effort to prevent catastrophic musculoskeletal injuries in this population of horses.

Next-generation sequencing promises major advancements in precision medicine but faces considerable challenges with insurance coverage. These challenges are especially important to address in oncology in which next-generation tumor sequencing (NGTS) holds a particular promise, guiding the use of life-saving or life-prolonging therapies. Payers’ coverage decision making on NGTS is challenging because this revolutionary technology pushes the very boundaries of the underlying framework used in coverage decisions. Some experts have called for the adaptation of the coverage framework to make it better equipped for assessing NGTS. Medicare’s recent decision to cover NGTS makes this topic particularly urgent to examine. In this article, we discussed the previously proposed approaches for adaptation of the NGTS coverage framework, highlighted their innovations, and outlined remaining gaps in their ability to assess the features of NGTS. We then compared the three approaches with Medicare’s national coverage determination for NGTS and discussed its implications for US private payers as well as for other technologies and clinical areas. We focused on US payers because analyses of coverage approaches and policies in the large and complex US health care system may inform similar efforts in other countries. We concluded that further adaptation of the coverage framework will facilitate a better suited assessment of NGTS and future genomics innovations.

OBJECTIVES: To examine the temporal trajectory of insurance coverage for next-generation tumor sequencing (sequencing) by private US payers, describe the characteristics of coverage adopters and nonadopters, and explore adoption trends relative to the Centers for Medicare and Medicaid Services’ National Coverage Determination (CMS NCD) for sequencing. METHODS: We identified payers with positive coverage (adopters) or negative coverage (nonadopters) of sequencing on or before April 1, 2019, and abstracted their characteristics including size, membership in the BlueCross BlueShield Association, and whether they used a third-party policy. Using descriptive statistics, payer characteristics were compared between adopters and nonadopters and between pre-NCD and post-NCD adopters. An adoption timeline was constructed. RESULTS: Sixty-nine payers had a sequencing policy. Positive coverage started November 30, 2015, with 1 payer and increased to 33 (48%) as of April 1, 2019. Adopters were less likely to be BlueCross BlueShield members (P < .05) and more likely to use a third-party policy (P < .001). Fifty-eight percent of adopters were small payers. Among adopters, 52% initiated coverage pre-NCD over a 25-month period and 48% post-NCD over 17 months. CONCLUSIONS: We found an increase, but continued variability, in coverage over 3.5 years. Temporal analyses revealed important trends: the possible contribution of the CMS NCD to a faster pace of coverage adoption, the interdependence in coverage timing among BlueCross BlueShield members, the impact of using a third-party policy on coverage timing, and the importance of small payers in early adoption. Our study is a step toward systematic temporal research of coverage for precision medicine, which will inform policy and affordability assessments.

Precision medicine is poised to have an impact on patients, health care delivery systems and research participants in ways that were only imagined 15 years ago when the human genome was first sequenced. While discovery using genome-based technologies has accelerated, these have only begun to be adopted into clinical medicine. Here we define precision medicine and the stakeholder ecosystem required to enable its integration into research and health care. We explore the intersection of data science, analytics and precision medicine in creating a learning health system that carries out research in the context of clinical care and at the same time optimizes the tools and information used to delivery improved patient outcomes. We provide examples of real world impact, and conclude with a policy and economic agenda that will be necessary for the adoption of this new paradigm of health care both in the United States and globally.

Two dogs were evaluated for clinical signs including dysuria, stranguria, and/or dyschezia. Physical examination findings were consistent with a caudal abdominal and intra-pelvic mass. Imaging with abdominal ultrasonography confirmed the presence of a tubular fluid-filled structure. In 1 dog computed tomography identified the fluid-filled structure to be the vagina and hydrocolpos was suspected. Endoscopic evaluation of the urogenital tracts identified imperforate vaginas in both dogs, and endoscopic-guided laser ablation was used to create a vaginal opening into the vestibule. Initial response to treatment was positive in both dogs, although 1 dog developed a recurrence of hydrocolpos 1-month after treatment. Endoscopic laser ablation provided a minimally invasive option for opening an imperforate vagina and no procedural complications occurred. Further evaluation is needed to determine the long-term effectiveness of this procedure.

The Eating Disorder Examination Questionnaire (EDE-Q; Fairburn & Cooper, 1993; Fairburn, Cooper, & O’Connor, 2008) is a well-established self-report instrument that measures eating disorder behaviors and attitudes, and is derived from the Eating Disorder Examination (EDE) interview (Fairburn & Cooper, 1993; Fairburn et al., 2008). The EDE-Q is relatively brief and cost-efficient, and is used for research and clinical purposes. Normative data are needed for appropriate analysis and interpretation of EDE-Q scores. Additionally, normative data provides a baseline distribution in a representative sample of individuals with eating disorders and establishes a baseline for comparison to healthy controls and individuals who have recovered from an eating disorder. Currently, normative data exists in a myriad of adult populations such as undergraduate students (Darcy, Hardy, Lock, Hill, & Peebles, 2013; Keane, Clarke, McGrath, Farrelly, & MacHale, 2017; Kelly, Cotter, & Mazzeo, 2012; Lavender, De Young, & Anderson, 2010; Luce & Crowther, 1999; Luce, Crowther, & Pole, 2008; Nakai et al., 2014; Quick & Byrd-Bredbenner, 2013; Reas, Overas, & Ro, 2012; Ro, Reas, & Lask, 2010; Villarroel, Penelo, Portell, & Raich, 2011), community samples (Hilbert, de Zwaan, & Braehler, 2012; Machado et al., 2014; Mond, Hay, Rodgers, & Owen, 2006; Mond, Hay, Rodgers, Owen, & Beumont, 2004), eating disorder (ED) samples (Brewin, Baggott, Dugard, & Arcelus, 2014; Dahlgren, Stedal, & Ro, 2017; Jennings & Phillips, 2017; Smith et al., 2017), and both ED and community samples (Aardoom, Dingemans, Slof Op’t Landt, & Van Furth, 2012; Welch, Birgegard, Parling, & Ghaderi, 2011). Few studies have examined normative data in adolescent populations. Normative EDE-Q data are available for healthy adolescent girls in the United Kingdom (Carter, Stewart, & Fairburn, 2001) and Portugal (Machado et al., 2014), and healthy adolescent boys and girls in Australia (Mond et al., 2014), Malaysia (Musa et al., 2016), and Mexico (Penelo, Negrete, Portell, & Raich, 2013). One Swedish study (Mantilla & Birgegard, 2016) reported norms on clinical and healthy adolescents using a 14-day time frame version of the EDE-Q, which had been specifically modified for adolescents (Carter et al., 2001). To the knowledge of these researchers, despite increased research and clinical use of the EDE-Q in adolescent populations, normative data in a clinical sample in the United States (U.S.) has not been published. Thus, the purpose of the present study was to provide EDE-Q norms for a sample of adolescent females diagnosed with anorexia nervosa (AN) admitted to inpatient treatment for an eating disorder.

10594 Background: The accessibility of cancer hereditary syndrome testing has increased, and the cost has declined significantly in the past few years. We conducted a national, quantitative survey of genetic counselors (GCs) to assess their perspectives on what influences hereditary cancer genetic testing decisions and practices, with a focus on cost. This survey was funded by NIH, conducted by UCSF TRANSPERS, and supported by the National Society of Genetic Counselors (NSGC). Methods: The survey was developed through literature review, expert interviews, and a pilot. Sent to the NSGC Cancer Special Interest Group via email. Chi-square tests were used to examine variability. Results: The survey response rate was 56% (202/363). Multiple hereditary cancer syndrome tests are discussed often/always by 86% of genetic counselors (GCs). The existence of an institutional protocol on multiple hereditary cancer syndrome testing was reported by 35.4% of GCs. When asked about GC counseling encounters, GCs report insurance rarely/never pays for: 25.2% pre-test in-person, 39.7% for pre-test tele-genetics, 35.4% post-test in-person, and 52.9% post-test tele-genetics. GCs rated clinical factors higher than cost as influencing decision for multiple hereditary syndrome cancer testing (table); the total cost of the test was least important. These patterns were similar across the GCs institution types and years in practice. Conclusions: We found consistent use of multiple hereditary cancer syndrome tests, with less focus on cost, out-of-pocket, and insurance coverage and more of a focus on clinical indicators. GCs reported challenges with reimbursement for GC counseling encounters. The shift toward more genetic counseling encounters via tele-genetics necessitates evaluation of insurance reimbursement.[Table: see text]

Aim The purpose of this study was to examine nurses' use and knowledge of caffeine and high energy drinks (HED) in three countries. Methods Nurses in each country completed a survey on caffeine and HED use and knowledge. Results In a sample of 182 nurses, caffeine use was high with 92% of nurses in Korea, 90.8% in Italy and 88.1% in the United States (US) having at least one cup of coffee a day while 64% of Koreans and 11.9% of those in the US had at least one HED per day. In Korea 68% of nurses (Italy 63.1% and 35.8% US) had at least one cup of caffeinated tea per day. Most agreed there is a need to educate nurses about HED, which contain high amounts of caffeine. Over half of nurses in Korea (58%) and the US (56.7%) said their colleagues consume HED at work. Conclusion Findings of this study indicate many nurses are consuming caffeine at work and there is a need for education. It is unclear how caffeine affects nurses' clinical performance, which raises the issue of patient safety. Further research is needed regarding safe amounts of caffeine while nurses are on the job as well as an understanding of how HED additives may affect the well-being and clinical care of nurses.

Background Positron emission tomography (PET) is a cross-sectional, functional imaging modality that has recently become available to the horse. The use of 18 F-sodium fluoride (18 F-NaF), a PET bone tracer, has not previously been reported in this species. Objectives To assess the feasibility of 18 F-NaF PET in the equine distal limb and explore possible applications in the horse in comparison with other imaging modalities. Study design Exploratory descriptive study involving three research horses. Methods Horses were placed under general anaesthesia prior to intravenous (i.v.) administration of 1.5 MBq/kg of 18 F-NaF. Positron emission tomography imaging of both front feet and fetlocks was performed using a portable scanner. Computed tomography (CT) of the distal limb was performed under a separate anaesthetic episode. Bone scintigraphy and magnetic resonance imaging (MRI) were subsequently performed under standing sedation. Images obtained from PET and other imaging modalities were independently assessed and the results correlated. Results Positron emission tomography images were obtained without complication. The radiation exposure rate was similar to equine bone scintigraphy. Positron emission tomography detected focal 18 F-NaF uptake in areas where other imaging modalities did not identify any abnormalities. This included sites of ligamentous attachment, subchondral compact bone plate and the flexor cortex of the navicular bone. 18 F-NaF uptake was identified in some, but not all, osseous fragments and areas of osseous formation, suggesting a distinction between active and inactive lesions. Main limitations A small number of horses were included and histopathology was not available. Conclusions 18 F-NaF PET imaging of the equine distal limb provides useful additional information when compared with CT, MRI and scintigraphy and has the potential for both research and clinical applications in the horse. The Summary is available in Chinese - see Supporting information.

© 2017 Future Medicine Ltd. Aim: Since whole-genome sequencing (WGS) information can have positive and negative personal utility for individuals, we examined predictors of willingness to pay (WTP) for WGS. Patients & methods: We surveyed two independent populations: adult patients (n = 203) and college seniors (n = 980). Ordinal logistic regression models were used to characterize the relationship between predictors and WTP. Results: Sex, age, education, income, genomic knowledge and knowing someone who had genetic testing or having had genetic testing done personally were associated with significantly higher WTP for WGS. After controlling for income and education, males were willing to pay more for WGS than females. Conclusion: Differences in WTP may impact equity, coverage, affordability and access, and should be anticipated by public dialog about related health policy.

Purpose:To explore the extent to which factors that determine performance transfer within and between time-trial and mass-start events in the track-cycling Omnium.Methods:Official finish rank in the 3 time-trial events, in the 3 mass-start events, and in the competition overall were collated in 20 international Omnium competitions between 2010 and 2014 for 196 male and 140 female cyclists. Linear mixed modeling of the log-transformed finish time for the time-trial events and of log-transformed finish rank for all events and final rank provided estimates of within-athlete race-to-race changes in performance and average betweenathletes differences across a season. These estimates were converted to various correlations representing relationships within and between the various events and final rank.Results:Intraclass correlation coefficients, representing race-to-race reproducibility of performance, were similar whether derived from finish rank or finish time for the time-trial events. Log-transformed finish ranks are therefore a suitable measure to assess and compare performance in time-trial and mass-start events. Omnium cyclists were more predictable in their performances from race to race in the timed events, whereas reduced predictability was observed in mass-start events. Interevent correlations indicated stronger links in performance between the timed disciplines, whereas performance in any of the mass-start events had only a slight positive relationship with performance in the other massstart events and little or no relationship with the timed events.Conclusions:Further investigation is warranted to determine whether factors related to performance in mass-start events can be identified to improve reproducibility or whether variability in performance results from random chance.

Background: Hereditary cancer panels (HCPs), testing for multiple genes and syndromes, are rapidly transforming cancer risk assessment but are controversial and lack formal insurance coverage. We aimed to identify payers' perspectives on barriers to HCP coverage and opportunities to address them. Comprehensive cancer risk assessment is highly relevant to the Precision Medicine Initiative (PMI), and payers' considerations could inform PMI's efforts. We describe our findings and discuss them in the context of PMI priorities. Methods: We conducted semi-structured interviews with 11 major US payers, covering >160 million lives. We used the framework approach of qualitative research to design, conduct, and analyze interviews, and used simple frequencies to further describe findings. Results: Barriers to HCP coverage included poor fit with coverage frameworks (100%); insufficient evidence (100%); departure from pedigree/family history-based testing toward genetic screening (91%); lacking rigor in the HCP hybrid research/clinical setting (82%); and patient transparency and involvement concerns (82%). Addressing barriers requires refining HCP-indicated populations (82%); developing evidence of actionability (82%) and pathogenicity/penetrance (64%); creating infrastructure and standards for informing and recontacting patients (45%); separating research from clinical use in the hybrid clinical-research setting (44%); and adjusting coverage frameworks (18%). Conclusions: Leveraging opportunities suggested by payers to address HCP coverage barriers is essential to ensure patients' access to evolving HCPs. Our findings inform 3 areas of the PMI: addressing insurance coverage to secure access to future PMI discoveries; incorporating payers' evidentiary requirements into PMI's research agenda; and leveraging payers' recommendations and experience to keep patients informed and involved.

Objective To determine the safety and efficacy of caudal cervical articular process joint arthroscopy by using needle arthroscopy in standing sedated horses. Study design Prospective experimental case series. Animals Six adult horses. Methods Three horses underwent exploration of bilateral C5-6 vertebral articular process joints and three bilateral C6-7 articular process joints by using a 1.2 × 65-mm needle arthroscope under standing sedation. The 16-gauge arthroscopic trocar and canula assembly was inserted in the desired articular process joint under ultrasonographic guidance without distention of the joint. Results All 12 articular process joints were successfully explored. Entering the joint on the first attempt was achieved in 10 of 12 joints. A craniodorsal approach for arthroscope insertion allowed evaluation of the most cranial aspect of the articular cartilage surface. Triangulation with a spinal needle was determined to be difficult and resulted in a limited space for movement. Conclusion Needle arthroscopy of the caudal cervical facet joints was performed safely and efficiently in standing sedated horses. Clinical significance Standing cervical articular process needle arthroscopy is a minimal morbidity technique with the potential to be an advantageous technique for the diagnosis and treatment of cervical articular process pathology.

Exome sequencing (ES) has the potential to improve management of congenital anomalies and neurodevelopmental disorders in fetuses, infants, and children. US payers are key stakeholders in patient access to ES. We examined how payers view insurance coverage and clinical utility of pediatric and prenatal ES.We employed the framework approach of qualitative research to conduct this study. The study cohort represented 14 payers collectively covering 170,000,000 enrollees.Seventy-one percent of payers covered pediatric ES despite perceived insufficient evidence because they saw merit in available interventions or in ending the diagnostic odyssey. None covered prenatal ES, because they saw no merit. For pediatric ES, 50% agreed with expanded aspects of clinical utility (e.g., information utility), and 21% considered them sufficient for coverage. For prenatal ES, payers saw little utility until in utero interventions become available.The perceived merit of ES is becoming a factor in payers' coverage for serious diseases with available interventions, even when evidence is perceived insufficient. Payers' views on ES's clinical utility are expanding to include informational utility, aligning with the views of patients and other stakeholders. Our findings inform clinical research, patient advocacy, and policy-making, allowing them to be more relevant to payers.

Author(s): Zakinova, Angela; Long-Boyle, Janel R; French, Deborah; Croci, Rhiannon; Wilson, Leslie; Phillips, Kathryn A; Kroetz, Deanna L; Shin, Jaekyu; Tamraz, Bani | Abstract: Introduction:Genetic-guided selection of non-oncologic medications is not commonly practiced in general, and at University of California, San Francisco (UCSF) Health, specifically. Understanding the unique position of clinicians with respect to clinical pharmacogenetics (PG) at a specific institution or practice is fundamental for implementing a successful PG consult service. Objectives:To assess clinicians' current practices, needs, and interests with respect to clinical PG at UCSF Health, a large tertiary academic medical center. Methods:A list of 42 target medications with clinical PG recommendations was complied. Clinical specialties that routinely used the target medications were identified. A 12-question survey focused on practice of PG for target medications was developed. Pharmacists and physicians were surveyed anonymously in several clinical specialties. Survey results were analyzed using descriptive statistics. Results:Of the 396 clinicians surveyed, 76 physicians and 59 pharmacists participated, resulting in 27% and 50% average response rates, respectively. The current use of PG in clinical practice for physicians and pharmacists was 29% and 32%, respectively, however this number varied across clinical specialties from 0% to 80%. Of clinicians whom reported they do not currently apply PG, 63% of physicians and 54% of pharmacists expressed interest in integrating PG. However, the level of interest varied from 20% to 100% across specialties. Of the respondents, 64% of physicians and 56% of pharmacists elected to provide contact information to investigators to further discuss their interest related to clinical PG. Conclusions:While PG is not uniformly practiced at UCSF Health, there is considerable interest in utilizing PG by the respondents. Our approach was successful at identifying clinicians and services interested in PG for specific drug-gene pairs. This work has set a foundation for next steps to advance PG integration at UCSF Health. Clinicians can adopt our approach as preliminary work to build a clinical PG program at their institutions.

An 8 yr old female spayed poodle/terrier mixed-breed dog was referred for evaluation of a recurrent and metastatic ovarian dysgerminoma. A total dose of 20Gy was administered to both the mediastinal metastatic lesion and retroperitoneal recurrent dysgerminoma in five daily fractions of 4Gy. Acute side effects were mild and self-limiting. This was followed by several courses of chemotherapy using a variety of agents. Despite extensive disease, this patient was still alive at the time of publication, 524 days after presentation and 501 days following completion of radiation. This case report demonstrates tolerability and efficacy of palliative radiation and chemotherapy for this rare tumor type.

Objective To evaluate the diagnostic and therapeutic utility of bronchoscopy in dogs undergoing computed tomography (CT) and surgery for intrathoracic disease (pyothorax and pneumothorax) secondary to migrating plant awns (MPA) and to report outcomes in dogs that did and did not undergo bronchoscopy in addition to CT and surgery. Study design Retrospective case series. Animals Thirty-seven client-owned dogs. Methods Medical records from 2008 to 2017 were reviewed for dogs with documented MPA in the thoracic cavity treated with CT and surgery with or without bronchoscopy. Information regarding diagnostics, treatments, complications, and outcomes relating to hospitalization was evaluated. Results At least one abnormal lung lobe was identified by CT in all dogs. Bronchial abnormalities were identified with bronchoscopy in 21 of 22 dogs (95.4%) with available reports. Agreement between CT and bronchoscopy findings ranged from 50% to 81.8%, depending on lung lobe. Thirty-six dogs had one or more lung lobes surgically removed. Thirty-seven MPA were retrieved via bronchoscopy in 10 of 27 (37%) dogs, and 39 MPA were retrieved at surgery in 26 of 37 (70.3%) dogs. Actinomyces spp. were cultured from surgical samples in 7 of 33 (21.2%) dogs. Thirty-five of 37 (94.6%) dogs survived to discharge. Conclusion Migrating plant awns were successfully retrieved via bronchoscopy. Agreement between CT findings and bronchoscopy was inconsistent, so there may be roles for both modalities. Short- and long-term survival was excellent in this cohort. Clinical significance Bronchoscopy may allow for diagnostic and therapeutic advantages compared with CT in dogs with endobronchial MPA. Actinomyces spp appear to be variably present in surgically acquired bacterial cultures in dogs with MPA.

Previously published myelographic studies do not report findings at the junction between the seventh cervical (C7) and first thoracic vertebrae (T1). Modern digital radiographic equipment allows improved visualization of C7-T1. Based on clinical experience, we hypothesized that 50% reduction of the dorsal myelographic column or 20% reduction of the dural diameter, criteria commonly used as a supportive finding for spinal cord compression in the cervical vertebral column, do not apply at C7-T1. A myelographic study was performed on 12 healthy, neurologically normal horses. Our hypothesis was confirmed; using established criteria eight of 12 horses would have been classified as having evidence of spinal cord compression at C7-T1. The dorsal myelographic column reduction at C7-T1 was 48 ± 12%, while the C6-C7 dorsal myelographic column reduction was 33 ± 17% (mean ± standard deviation) (P=0.010). The dural diameter reduction at C7-T1 (22.0 ± 6.7%) was significantly greater than the dural diameter reduction at C6-C7 (13.2 ± 9.5%) (P=0.0007). Further measurements and comparisons suggested that the apparent greater reduction of dorsal myelographic column and dural diameter at C7-T1 was due to larger intravertebral measurements at C7 rather than smaller intervertebral values at C7-T1. Based on these findings, alternative criteria should be used at C7-T1 when assessing clinical cases for cervical stenotic myelopathy. Reduction of the dorsal myelographic column by 60% or of the dural diameter by 30% would avoid high numbers of false positive myelographic cases at C7-T1.

Purpose: To further the understanding of elite athlete performance in complex race environments by examining the changes in cyclists’ performance between solo time trials and head-to-head racing in match-sprint tournaments. Methods: Analyses were derived from official results of cyclists in 61 elite international sprint tournaments (2000–2016), incorporating the results of 2060 male and 1969 female head-to-head match races. Linear mixed modeling of log-transformed qualification and finish ranks was used to determine estimates of performance predictability as intraclass correlation coefficients. Correlations between qualifying performance and final tournament rank were also calculated. Chances of winning head-to-head races were estimated adjusting for the difference in the cyclists’ qualifying times. All effects were evaluated using magnitude-based inference. Results: Minor differences in predictability between qualification time trial and final tournament rank were suggestive of more competitiveness among men in the overall tournament. Performance in the qualification time trial was strongly correlated with, but not fully indicative of, performance in the overall tournament. Correspondingly, being the faster qualifier had a large positive effect on the chances of winning a head-to-head race, but small substantial differences between riders remained after adjustment for time-trial differentials. Conclusions: The present study provides further insight into how real-world competition data can be used to investigate elite athlete performance in sports where athletes must directly interact with their opponents. For elite match-sprint cyclists, qualifying time-trial performance largely determines success in the overall tournament, but there is evidence of a consistent match-race ability that modifies the chances of winning head-to-head races.

OBJECTIVE To describe vertebral left atrial size (VLAS), a quantitative method to estimate left atrial (LA) size radiographically, and to determine its diagnostic value for prediction of echocardiographic LA enlargement in dogs with myxomatous mitral valve disease (MMVD) of varying severity. DESIGN Prospective observational study. ANIMALS 103 client-owned dogs with a left-sided systolic murmur. PROCEDURES For each dog, 3-view thoracic radiographs were obtained within 24 hours of an echocardiographic examination. The VLAS was measured on right and left lateral thoracic radiographs and compared with the left atrium-to-aortic root ratio acquired from short-axis (LA:AoSx) and long-axis (LA:AoLx) echocardiographic images. Left atrial enlargement was defined as an LA:AoLx ≥ 2.6 or LA:AoSx ≥ 1.6. Dogs were allocated to 4 groups on the basis of MMVD severity. RESULTS Of the 103 dogs, 15, 40, 26, and 22 were assigned to the control (no echocardiographic abnormalities), stage B1 (hemodynamically irrelevant MMVD), B2 (hemodynamically relevant MMVD), and C-D (MMVD with congestive heart failure) groups, respectively. Median VLAS, LA:AoSx, and LA:AoLx for the stage B2 and C-D groups were significantly greater than the corresponding medians for the control and stage B1 groups. There was a moderate positive correlation between VLAS and both LA:AoSx and LA:AoLx. Receiver operating characteristic analyses revealed that a VLAS ≥ 2.3 vertebrae was a useful predictor of LA enlargement. Intraobserver and interobserver agreements for VLAS measurements were high. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated VLAS was a repeatable and useful radiographic measurement for prediction of LA enlargement in dogs with MMVD.

Squamous cell carcinoma has been reported in a variety of bird species, most commonly psittacine and gallinaceous birds. The long-term prognosis in nongallinaceous birds is generally poor if complete surgical excision is not possible. Squamous cell carcinoma of the rhinotheca was diagnosed in a 34-year-old timneh African grey parrot (Psittacus timneh) with a 2-year history of beak abnormalities. No evidence of metastasis or local invasion were found on results of radiographs or computed tomography scan. The bird was treated with surgical debulking and palliative megavoltage radiation therapy. After 4 radiation treatments, the affected tissue was necrotic and was debrided to reveal healthy granulation tissue. The bird died approximately 7 months after diagnosis and 4 months after cessation of radiation treatment. At the time of death, a small scab lesion remained at the left oral commissure, but no visible tumor regrowth was evident. A postmortem examination was not performed, however, and tumor recurrence could not be ruled out in this bird.

Behavioral health problems are common, yet most patients do not receive effective treatment in primary care settings. Despite availability of effective models for integrating behavioral health care in primary care settings, uptake has been slow. The Behavioral Health Integration Implementation Guide provides practical guidance for adapting and implementing effective integrated behavioral health care into patient-centered medical homes. The authors gathered input from stakeholders involved in behavioral health integration efforts: safety net providers, subject matter experts in primary care and behavioral health, a behavioral health patient and peer specialist, and state and national policy makers. Stakeholder input informed development of the Behavioral Health Integration Implementation Guide and the GROW Pathway Planning Worksheet. The Behavioral Health Integration Implementation Guide is model neutral and allows organizations to take meaningful steps toward providing integrated care that achieves access and accountability.

A 10-year-old female koi subspecies ( Cyprinus carpio ) was presented with bilateral, asymmetric, sessile masses of the periventiductal tissue. The owner had first observed the masses for approximately 1 year before seeking a veterinary evaluation of the fish. Over the past year, the sessile masses continued to grow and develop in size. An incisional biopsy was performed under general anesthesia to further assess the abnormal tissue structures. Based on the histologic evaluation of the submitted biopsy sample, the growth was determined to be a benign spindle cell neoplasm. The koi also was diagnosed with a concurrent genital tract infection based on cytological examination of the reproductive tract fluid. Following transport to the Veterinary Medical Teaching Hospital for further evaluation, a coelomic ultrasound revealed local infiltration of the tissue to the surrounding tissue. To decrease the risks of recurrence following surgical debulking, chemotherapy was recommended to treat the tissue adjacent to the tumor. Cultures obtained from the genital pore resulted in the isolation of Aeromonas spp. susceptible to ceftiofur, which was elected as a preemptive antibiotic. Surgical debulking of the mass was performed, and bleomycin was administered intralesionally and at the periphery of the surgical site. The koi recovered successfully from anesthesia and was discharged later the same day and prescribed an analgesic regimen of meloxicam. After further histological examination of the submitted tissue samples from the periventiductal growths, the tumor was identified as a leiomyoma. No recurrence of the mass was detected 6 months following the surgical procedure and chemotherapy.

Nurses experience high rates of violence on the job, which is a significant stressor. Stress can alter nurses' care of patients, but stress can be mitigated by resilience. The purpose of this study was to examine the relationship between nurses' resilience levels and their reports of patient care following episodes of workplace violence. Six themes emerged from nurses' (n = 57) responses to workplace violence: vigilance, cautious yet individualized with care, part of the job, growth, jaded, and no effect. Low resilience levels were found in nurses with themes of feeling jaded, cautious yet individualized with care, and vigilance. High resilience levels were found in nurses with themes of no effect, growth, cautious yet individualized with care, and vigilance. Nurses' resilience scores were related to their patient care descriptions after episodes of workplace violence. Raising nurses' resilience levels through training might help them to positively overcome the effects of workplace violence, limiting impacts to patient care.

© 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research Background: Clinical use of next-generation sequencing (NGS) tests has been increasing, but few studies have examined their economic value. Several studies have noted that there are methodological challenges to conducting economic evaluations of NGS tests. Objective: Our objective was to examine key methodological challenges for conducting economic evaluations of NGS tests, prioritize these challenges for future research, and identify how studies have attempted solutions to address these challenges. Methods: We identified challenges for economic evaluations of NGS tests using prior literature and expert judgment of the co-authors. We used a modified Delphi assessment to prioritize challenges, based on importance and probability of resolution. Using a structured literature review and article extraction we then assessed whether published economic evaluations had addressed these challenges. Results: We identified 11 challenges for conducting economic evaluations of NGS tests. The experts identified three challenges as the top priorities for future research: complex model structure, timeframe, and type of analysis and comparators used. Of the 15 published studies included in our literature review, four studies described specific solutions relevant to five of the 11 identified challenges. Conclusions: Major methodological challenges to economic evaluations of NGS tests remain to be addressed. Our results can be used to guide future research and inform decision-makers on how to prioritize research on the economic assessment of NGS tests.

A 17-yr-old, 22.2-kg, intact female sulcata tortoise (Centrochelys sulcata) was presented for evaluation of a suspected intestinal obstruction and a 2-month history of hind-limb weakness, anorexia, lack of defecation, and decreased urine production. Clinical signs included generalized subcutaneous edema, pelvic limb paresis, decreased vent tone, and ataxia. Computed tomography (CT) identified findings consistent with a chronic compression fracture of the eighth cervical vertebrae with severe extradural compression of the spinal cord and near-complete obliteration of the vertebral canal. The tortoise was medically managed in the hospital for 13 days and discharged with analgesic and antibiotic medications. Over the following weeks, the tortoise regained an ability to defecate and urinate, and the tortoise's motor deficits mildly improved. A recheck contrast CT at 39 wk postdischarge was consistent with remodeling of the chronic compression fracture and mildly improved extradural compression of the spinal cord. Approximately 2 yr after the initial presentation, the motor limb deficits were still present. Thirty-three months after initial presentation, the tortoise presented obtunded and with anasarca. The tortoise was euthanized, and the necropsy revealed bilateral demyelination with moderate axonal loss, astrocyte reactivity, and moderate dural fibrosis in the spinal cord, consistent with chronic compression at the level of C8. This report illustrates an unusual presentation of a chronic cervical vertebral fracture and spinal cord compression that was diagnosed and monitored via CT, the treatment and recovery of most of the initial clinical signs and persistent motor limb deficits, as well as the postmortem spinal cord histologic findings.

Purpose Whole Exome Sequencing (WES) is being adopted for neurodevelopmental disorders in pediatric patients. However, little is known about current coverage policies or the evidence cited supporting these policies. Our study is the first in-depth review of private payer WES coverage policies for pediatric patients with neurodevelopmental disorders. Methods We reviewed private payer coverage policies and examined evidence cited in the policies of the 15 largest payers in 2017, and trends in coverage policies and evidence cited (2015 – 2017) for the five largest payers. Results There were four relevant policies (N=5 payers) in 2015 and 13 policies (N=15 payers) in 2017. In 2015, no payer covered WES, but by 2017, three payers from the original registry payers did. In 2017, eight of the 15 payers covered WES. We found variations in the number and types of evidence cited. Positive coverage policies tended to include a larger number and range of citations. Conclusion We conclude that more systematic assessment of evidence cited in coverage policies can provide a greater understanding of coverage policies and how evidence is used. Such assessments could facilitate the ability of researchers to provide the needed evidence, and the ability of clinicians to provide the most appropriate testing for patients.

A major challenge to adoption of personalized medicine approaches, such as pharmacogenomics, is that data to address many critical questions relevant to clinical application, economics, policy and regulation are typically unavailable or widely dispersed. The evidence base we tentatively call Evaluation Data for Assessing Personalized Medicine Translation (EDAPT) would generate the foundation for a database of information. This article begins with a description of the rationale and conceptual framework for this effort.

BiDil

This study aimed to critically appraise the current level of economic evidence available for thiopurine S-methyltransferase (TPMT) testing of thiopurine drugs, such as azathioprine. Six economic evaluations of testing were identified, which all recommended that TPMT testing is a cost-effective use of healthcare resources. Critical appraisal, using published guidelines, showed potential limitations in model structures, approaches to data analysis and input parameters, which were mainly based on expert opinion. Where data did exist these were from retrospective studies. To conduct economic evaluations with more robust findings, decision analysts need good quality data for the following key parameters: current prevalence of profound neutropenia among patients prescribed thiopurine drugs; mean length of related hospitalization and clinical outcome; impact of introducing the test on clinical pathways in terms of resource use; and clinical effectiveness data in terms of number of cases of neutropenia averted and subsequent impact on mortality and health-related quality of life. An iterative approach may be used to stimulate the production of a sufficient evidence base for innovative technologies, such as pharmacogenetic testing. Such an iterative approach involves starting with simple models using available existing clinical and resource use data, as in the case of TPMT testing. The use of formal value of information methods may guide the decision whether prospective studies are required to address uncertainties in the key parameters driving the model results. The results from well-designed prospective studies can then be used to populate more complex economic models.

Objective To summarize lessons learned while analyzing the costs of integrating whole genome sequencing into the care of cardiology and primary care patients in the MedSeq Project by conducting the first randomized controlled trial of whole genome sequencing in general and specialty medicine. Methods Case study that describes key methodological and data challenges that were encountered or are likely to emerge in future work, describes the pros and cons of approaches considered by the study team, and summarizes the solutions that were implemented. Results Major methodological challenges included defining whole genome sequencing, structuring an appropriate comparator, measuring downstream costs, and examining clinical outcomes. Discussions about solutions addressed conceptual and practical issues that arose because of definitions and analyses around the cost of genomic sequencing in trial-based studies. Conclusions The MedSeq Project provides an instructive example of how to conduct a cost analysis of whole genome sequencing that feasibly incorporates best practices while being sensitive to the varied applications and diversity of results it may produce. Findings provide guidance for researchers to consider when conducting or analyzing economic analyses of whole genome sequencing and other next-generation sequencing tests, particularly regarding costs.

Genetic testing and spending on that testing have grown rapidly since the mapping of the human genome in 2003. However, it is not widely known how many tests there are, how they are used, and how they are paid for. Little evidence from large data sets about their use has emerged. We shed light on the issue of genetic testing by providing an overview of the testing landscape. We examined test availability and spending for the full spectrum of genetic tests, using unique data sources on test availability and commercial payer spending for privately insured populations, focusing particularly on tests measuring multiple genes in the period 2014-17. We found that there were approximately 75,000 genetic tests on the market, with about ten new tests entering the market daily. Prenatal tests accounted for the highest percentage of spending on genetic tests, and spending on hereditary cancer tests accounted for the second-highest. Our results provide insights for those interested in assessing genetic testing markets, test usage, and health policy implications, including current debates over the most appropriate regulatory and payer coverage mechanisms.

On 16 March, the Centers for Medicare and Medicaid Services (CMS) announced that Medicare will cover Food and Drug Administration (FDA)–approved or cleared genomic tests that encompass broad gene panels for advanced cancer patients ([ 1 ][1]). The final policy does not include the initial draft's

A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW-antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated-saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs.