Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse. In this commentary, members of the Global Economics and Evaluation of Clinical Genomics Sequencing Working Group (GEECS) describe the global landscape of CGS in the context of health economics and policy and propose evidence-based solutions to address existing and future barriers to CGS implementation. The topics discussed are reflected as two overarching themes: (1) system readiness for CGS and (2) evidence, assessments, and approval processes. These themes highlight the need for health economics, public health, and infrastructure and operational considerations; a robust patient- and family-centered evidence base on CGS outcomes; and a comprehensive, collaborative, interdisciplinary approach.

Posttraumatic growth in eating disorder recovery.

OBJECTIVE: To investigate posttraumatic growth in individuals recovering from an eating disorder. DESIGN: A convergent parallel mixed methods design was used. PARTICIPANTS: The sample consisted of 28 participants who completed the entire study and an additional 10 who completed only the quantitative portion of this mixed methods study. METHODS: The National Eating Disorders Association (NEDA) provided a link to the electronic survey via their website. Participants were asked to complete the Posttraumatic Growth Inventory (PTGI) and the Core Beliefs Inventory (CBI) in the quantitative strand. For the qualitative strand, participants were asked to describe any positive changes in their beliefs or life as the result of their eating disorder (ED). RESULTS: Participants reported a high amount of posttraumatic growth as indicated by their mean score on the CBI (30.39, SD 7.89) and (71.26, SD 16.58) on the PTGI. Qualitative categories included relating to others, personal strength, new possibilities, appreciation of life, and spiritual change. CONCLUSION: Participants described the transformation they experienced in the recovery process, with recovery from an eating disorder facilitating an opportunity for growth. Providing posttraumatic growth interventions may have the potential to help individuals with eating disorders find meaning in their pathway through recovery.

The State of State Biomarker Testing Insurance Coverage Laws.

This Viewpoint discusses laws mandating insurance coverage of biomarker testing to broaden access to care for patients with cancer.

Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner.

Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited. Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene Khdc3 have hepatic metabolic defects that persist over multiple generations. We find that genetically wild type females descended from Khdc3 mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages. This was associated with dysregulation of hepatically-metabolized molecules in the blood of these wild type mice with mutational ancestry. The oocytes of Khdc3-null females, as well as their wild type descendants, had dysregulation of multiple small RNAs, suggesting that these epigenetic changes in the gametes transmit the phenotype between generations. Our results demonstrate that ancestral mutation in Khdc3 can produce transgenerational inherited phenotypes, potentially indefinitely.

The restraint chair: A qualitative study of the patient experience.

Despite initiatives to eliminate restraint from acute psychiatric care, there remain times when violent episodes threaten the safety of patients and/or staff. The restraint chair may be used in these moments and provide an alternative to four-point restraint. The purpose of this study was to examine the patient experience of the restraint chair. Patients who had an episode of restraint in the restraint chair during their hospital stay were interviewed about the experience. Participants described the experience as "unpleasant," with the majority preferring the restraint chair to other methods of restraint they had experienced. Participants indicated they could "understand" why the restraint had occurred and felt staff were "helpful" and "create safety." Finally, participants stated the hospital experience was "positive." Although the goal remains to eliminate restraint, psychiatric settings may want to consider the restraint chair as an alternative to four-point restraint for situations requiring mechanical restraint. Nurses' presence and communication with patients during the restraint process is important to the patient experience. More research is needed to verify these results.

Clinical validity and utility of circulating tumor DNA (ctDNA) testing in advanced non-small cell lung cancer (aNSCLC): a systematic literature review and meta-analysis.

Purpose: Circulating tumor DNA (ctDNA) testing has become a promising tool to guide first-line (1L) targeted treatment for advanced non-small cell lung cancer (aNSCLC). This study aims to estimate the clinical validity (CV) and clinical utility (CU) of ctDNA-based next-generation sequencing (NGS) for oncogenic driver mutations to inform 1L treatment decisions in aNSCLC through a systematic literature review and meta-analysis. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Embase to identify randomized control trials or observational studies reporting CV/CU on ctDNA testing in patients with aNSCLC. Meta-analyses were performed using bivariate random-effects models to estimate pooled sensitivity and specificity. Progression-free/overall survival (PFS/OS) was summarized for CU studies. Results: Eighteen studies were identified: 17 CV only, 2 CU only, and 1 both. Thirteen studies were included for the meta-analysis on multi-gene detection. The overall sensitivity and specificity for ctDNA detection of any mutation were 0.69 (95% CI, 0.63-0.74) and 0.99 (95% CI, 0.97-1.00) respectively. However, sensitivity varied greatly by driver gene, ranging from 0.29 (95% CI, 0.13-0.53) for ROS 1 to 0.77 (95% CI, 0.63-0.86) for KRAS . Two studies compared PFS with ctDNA versus tissue-based testing followed by 1L targeted therapy found no significant differences. One study reported OS curves on ctDNA-matched and tissue-matched therapies but no hazard ratios were provided. Conclusion: ctDNA testing demonstrated an overall acceptable diagnostic accuracy in aNSCLC patients, however, sensitivity varied greatly by driver mutation. Further research is needed, especially for uncommon driver mutations, to better understand the CU of ctDNA testing in guiding targeted treatments for aNSCLC.

Ramifications of the COVID-19 Pandemic on Nursing Students' Transition to Practice.

As the COVID-19 pandemic altered the course of nursing education worldwide, it disrupted efforts to transition nursing students to professional practice. The investigators examined clinical nursing faculty members' assessment of senior students' practice strengths and challenges compared to graduates of prior years. Findings demonstrated COVID-19's wide-ranging impacts on nursing students' transition to practice and offered suggestions about the implications for nursing professional development practitioners.

The Health Inequality Impact of Liquid Biopsy to Inform First-Line Treatment of Advanced Non-Small Cell Lung Cancer: A Distributional Cost-Effectiveness Analysis.

OBJECTIVES: To perform a distributional cost-effectiveness analysis of liquid biopsy (LB) followed by, if needed, tissue biopsy (TB) (LB-first strategy) relative to a TB-only strategy to inform first-line treatment of advanced non-small cell lung cancer (aNSCLC) from a US payer perspective by which we quantify the impact of LB-first on population health inequality according to race and ethnicity. METHODS: With a health economic model, quality-adjusted life-years (QALYs) and costs per patient were estimated for each subgroup. Given the lifetime risk of aNSCLC, and assuming equally distributed opportunity costs, the incremental net health benefits of LB-first were calculated, which were used to estimate general population quality-adjusted life expectancy at birth (QALE) by race and ethnicity with and without LB-first. The degree of QALYs and QALE differences with the strategies was expressed with inequality indices. Their differences were defined as the inequality impact of LB-first. RESULTS: LB-first resulted in an additional 0.21 (95% uncertainty interval: 0.07-0.39) QALYs among treated patients, with the greatest gain observed among Asian patients (0.31 QALYs [0.09-0.61]). LB-first resulted in an increase in relative inequality in QALYs among patients, but a minor decrease in relative inequality in QALE. CONCLUSIONS: LB-first to inform first-line aNSCLC therapy can improve health outcomes. With current diagnostic performance, the benefit is the greatest among Asian patients, thereby potentially widening racial and ethnic differences in survival among patients with aNSCLC. Assuming equally distributed opportunity costs and access, LB-first does not worsen and, in fact, may reduce inequality in general population health according to race and ethnicity.

The Impact of Longitudinal Patterns of Adolescent Sleep Duration on Adult C-Reactive Protein (CRP), Waist-To-Height Ratio, and Body Mass Index (BMI) Among Black and White Individuals.

PURPOSE: To assess the impact of longitudinal adolescent sleep duration on adult C-reactive protein (CRP), waist-to-height ratio (WtHR), and body mass index (BMI) by race. METHODS: Participants (N = 2,399; Mage = 15.7; 40.2% male; 79.2% White, 20.8% Black; Grades 7-12 at Wave I) from the Add Health database provided self-reported sleep duration in Waves I-IV. During Wave V, CRP, WtHR, and BMI were objectively measured. Trajectory analysis was performed using a group-based modeling approach. Chi-square test determined racial differences between groups. General linear models determined relationships between trajectory group, race, and group/race interaction with Wave V CRP, WtHR, and BMI. RESULTS: Three sleep trajectories emerged: Group 1 "shortest" (24.4%), Group 2 "stable recommended" (67.6%), and Group 3 "varied" (8%). Black individuals and older individuals were more likely to be in Group 1 compared with Group 2. Regardless of race, individuals with patterns of sleep duration increasing to above what is recommended across waves (Group 3) had elevated CRP. Individuals with stable patterns of adequate sleep (Group 2) had lower WtHR. Black individuals with consistently stable patterns of adequate sleep duration had lower BMI compared to those with low sleep duration. DISCUSSION: Black individuals were more likely to obtain chronically short sleep during the transition from adolescence to adulthood, highlighting a significant health disparity. Poor longitudinal sleep predicted elevated CRP and WtHR. Sleep only impacted BMI for Black individuals. This may relate to racial differences in BMI measurement.

Pain-Related Stigma and Its Associations With Clinical and Experimental Pain Severity in Youth With Chronic Musculoskeletal Pain Conditions.

OBJECTIVE: Many children with chronic musculoskeletal pain conditions experience stigma which can have negative downstream consequences. This study compares ratings of clinical pain (current pain intensity and pain interference), experimental pain (temporal summation, cold water tolerance, and cold pain intensity), and pain-related stigma among three groups of youth with rheumatic conditions. The relations among ratings of pain-related stigma and pain variables were explored. METHODS: Eighty-eight youth aged 8-17 years with a diagnosis of juvenile idiopathic arthritis (JIA = 32), juvenile fibromyalgia (JFM = 31), or non-specific chronic pain (NSCP = 25) completed measures of clinical pain ratings (average 7-day pain intensity, day of assessment pain (DoA), and pain interference), experimental pain (cold pain tolerance, cold pain intensity, and temporal summation of mechanical pain), and pain-related stigma. Data analysis compared pain-related stigma and pain ratings across the three groups and examined the relations among pain-related stigma and pain ratings. RESULTS: Youth with JFM reported higher ratings of clinical pain and pain-related stigma than their counterparts with NSCP or JIA. However, there were no differences in experimental pain. Pain-related stigma was associated with greater ratings of pain interference, particularly for those with JIA and NSCP. Pain-related stigma was also associated with greater average daily pain intensity but not DoA. CONCLUSION: Youth with medically unexplained pain report greater stigma and worse pain than their peers; thus, robust assessment of pain in this population is necessary. Future work should longitudinally explore the impact of pain-related stigma on pain outcomes and treatment responses.

Private Payer and Medicare Coverage Policies for Use of Circulating Tumor DNA Tests in Cancer Diagnostics and Treatment.

BACKGROUND: Circulating tumor DNA (ctDNA) is used to select initial targeted therapy, identify mechanisms of therapeutic resistance, and measure minimal residual disease (MRD) after treatment. Our objective was to review private and Medicare coverage policies for ctDNA testing. METHODS: Policy Reporter was used to identify coverage policies (as of February 2022) from private payers and Medicare Local Coverage Determinations (LCDs) for ctDNA tests. We abstracted data regarding policy existence, ctDNA test coverage, cancer types covered, and clinical indications. Descriptive analyses were performed by payer, clinical indication, and cancer type. RESULTS: A total of 71 of 1,066 total policies met study inclusion criteria, of which 57 were private policies and 14 were Medicare LCDs; 70% of private policies and 100% of Medicare LCDs covered at least one indication. Among 57 private policies, 89% specified a policy for at least 1 clinical indication, with coverage for ctDNA for initial treatment selection most common (69%). Of 40 policies addressing progression, coverage was provided 28% of the time, and of 20 policies addressing MRD, coverage was provided 65% of the time. Non-small cell lung cancer (NSCLC) was the cancer type most frequently covered for initial treatment (47%) and progression (60%). Among policies with ctDNA coverage, coverage was restricted to patients without available tissue or in whom biopsy was contraindicated in 91% of policies. MRD was commonly covered for hematologic malignancies (30%) and NSCLC (25%). Of the 14 Medicare LCD policies, 64% provided coverage for initial treatment selection and progression, and 36% for MRD. CONCLUSIONS: Some private payers and Medicare LCDs provide coverage for ctDNA testing. Private payers frequently cover testing for initial treatment, especially for NSCLC, when tissue is insufficient or biopsy is contraindicated. Coverage remains variable across payers, clinical indications, and cancer types despite inclusion in clinical guidelines, which could impact delivery of effective cancer care.

Emergency Nurses' Care of Psychiatric Patients.

OBJECTIVE: The volume of patients with mental illness presenting to the emergency department (ED) has been increasing in recent years, yet many ED nurses hold stigmatized attitudes and behaviors about patients with mental illness, creating barriers to therapeutic care. At the same time, there has been an increase in workplace violence (WPV) against nurses. Fortunately, resilience helps nurses manage their response to WPV and continue to provide therapeutic care. Although research has considered many barriers to the therapeutic care of patients with mental illness in the ED, the variables of stigma, resilience, and the experience of WPV have not been considered in relation to behavioral care competence and work performance, which is the purpose of this study. METHODS: A survey consisting of the Brief Resilience Scale, the Individual Work Performance Questionnaire, the Behavioral Healthcare Competency (BHCC) survey, the Opening Minds Scale for Healthcare Providers, and open-ended questions about WPV were used to collect data. Independent t-tests were run between scale scores and categorical descriptive data. Correlations were run between scale scores and continuous descriptive data. RESULTS: Over half (60%) had experienced a personal injury from WPV. Higher behavioral competence scores were associated with lower stigma and higher contextual work performance. Nurses who experienced a WPV injury had higher mean BHCC and higher contextual work performance scores. CONCLUSIONS: WPV may be an impetus for nurses to improve their practice in behavioral health and working as part of a team.

Horner syndrome as a physiological biomarker of disease in canine cervical myelopathy.

BACKGROUND: Horner syndrome often occurs with cervical myelopathies and might provide insight into the underlying disease and prognosis. OBJECTIVES: To describe the clinical and imaging features of dogs with cervical myelopathy and concurrent Horner syndrome and to determine association of Horner syndrome with diseases or magnetic resonance images (MRI). ANIMALS: Ninety-three client-owned dogs with cervical myelopathy and concurrent Horner syndrome and 99 randomly selected client-owned dogs with cervical myelopathy without Horner syndrome (control cases). METHODS: Retrospective study. Medical records were reviewed to identify Horner and control cases and clinical findings recorded. MRI were reviewed, and lesions characterized and recorded. Descriptive and comparative statistics were performed. RESULTS: Non-compressive disease occurred more frequently in the Horner group compared with controls (58%; 95% CI: 48-68 vs 9%; 95% CI: 5-16; P < .0001). The most common diseases were fibrocartilaginous embolism in the Horner group (44/93; 47%) and intervertebral disc extrusion (76/99; 77%) amongst controls. On MRI, parenchymal hyperintensity was seen more commonly in the Horner group (95%; 95% CI: 88-98) compared with controls (51%; 95% CI: 41-60; P < .0001). In the Horner group, dogs that did not survive to discharge (N = 13) had more extensive MRI lesions relative to the adjacent vertebral length (200%; IQR 110%-575%) compared with survivors (N = 80; 110%; IQR 40%-250%; P = .02). Lateralization of Horner signs and MRI changes matched in 54% of cases. The overall survival rate was high in both Horner (80/93; 86%) and control (95/99; 96%) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Horner syndrome in cervical myelopathy is commonly associated with noncompressive intraparenchymal disease.

Validating Psychometric Properties of a Revised Patient Version of the Combined Assessment of Psychiatric Environments (CAPE).

BACKGROUND: Measuring patient experience is an essential challenge in the inpatient behavioral health population. AIM: This initiative analyzed the psychometric properties of a revised version of the patient Combined Assessment of Psychiatric Environments (p-CAPE-R) survey. METHODS: The p-CAPE was revised to encompass the interdisciplinary treatment team and implemented on five inpatient psychiatric units at an academic medical center. A psychometric analysis was performed on the p-CAPE-R. RESULTS: Analysis of factor loadings with a large sample (n = 786) revealed a more coherent item structure under the "staff competency and engagement" and "treatment effectiveness" domains than presented in the original instrument development research. CONCLUSIONS: Although the p-CAPE-R reflects a more useful and psychometrically sound instrument than the original p-CAPE, further analysis and revision to reflect the entire interdisciplinary team is warranted.

Eating Disorders: Identification and Management in General Medical and Psychiatric Settings.

OBJECTIVE: Eating disorders (EDs) are serious, complex illnesses with both behavioral and physical health features. EDs have high rates of medical and psychiatric morbidity, and a 6% mortality rate, the highest of any mental illness. Early detection of EDs offers the best opportunity for recovery; yet, estimates are that as few as one in 10 individuals with an ED receive treatment. The purpose of this article is to provide an ED identification and management overview for inpatient nurse clinicians in general psychiatric and medical settings, helping to facilitate timely recognition and care. METHOD: An overview of ED diagnostic criteria and two evidence-based ED tools are introduced for consideration. RESULTS: Opportunities to identify and help manage an ED are numerous. Most individuals with an ED make several health care visits in either medical or psychiatric settings without ever being screened for an ED. General ED screening and assessment tool familiarization can facilitate a treatment trajectory for these patients, improve overall quality of life, and may potentially result in a life-saving intervention for this often-deadly cluster of medical and psychiatric disorders. CONCLUSION: Screening and assessment in general clinical settings, identifying patients with undiagnosed EDs, beginning basic treatment plans, and referrals for appropriate follow-up care, have the potential to reduce ED recidivism and related health care costs. Simultaneously, and most important, long-term outcomes for patients with EDs may improve.

Introducing the inaugural issue of Health Affairs Scholar: Emerging and Global Health Policy (HAS).

We are delighted to introduce readers to the inaugural issue of Health Affairs Scholar: Emerging and Global Health Policy (HAS). HAS is the new fully open access companion journal to Health Affairs. Building on Health Affairs' reputation as the leading journal of health policy thought and research, HAS serves as an additional forum for high-quality, peer-reviewed work from researchers worldwide. The journal fills a gap by focusing on both health policy and emerging issues that are historically less often addressed in "legacy" health policy journals. HAS will elevate emerging new research and policy analysis on healthcare technology, business models, and innovation; population health; global health policy; and important intersecting topics with health, such as the impact of climate change. The journal will also cover core health policy topics of healthcare costs, access to care, quality, and equity.

Ten health policy challenges for the next 10 years.

Health policies and associated research initiatives are constantly evolving and changing. In recent years, there has been a dizzying increase in research on emerging topics such as the implications of changing public and private health payment models, the global impact of pandemics, novel initiatives to tackle the persistence of health inequities, broad efforts to reduce the impact of climate change, the emergence of novel technologies such as whole-genome sequencing and artificial intelligence, and the increase in consumer-directed care. This evolution demands future-thinking research to meet the needs of policymakers in translating science into policy. In this paper, the Health Affairs Scholar editorial team describes "ten health policy challenges for the next 10 years." Each of the ten assertions describes the challenges and steps that can be taken to address those challenges. We focus on issues that are traditionally studied by health services researchers such as cost, access, and quality, but then examine emerging and intersectional topics: equity, income, and justice; technology, pharmaceuticals, markets, and innovation; population health; and global health.