The association of varying treatment thresholds of mepolizumab on asthma exacerbations in adults.

Background: Asthma has a high healthcare burden globally, with up to 10% of the asthma population suffering from severe disease. Biologic agents are a newer class of asthma treatments for severe asthma, with good evidence for efficacy in clinical trials. Nevertheless, real-world studies of its impact on clinical outcomes are limited.Methods: This is an observational cohort study using administrative claims data. The study population consisted of patients aged ≥18 years who had a diagnosis of asthma and initiated mepolizumab after November 4, 2015 and had continuous medical and drug coverage in both the 365 days prior to and following mepolizumab initiation. In patients treated with mepolizumab, we described clinically significant asthma exacerbations by minimum continuous treatment thresholds following initiation of mepolizumab, medication switching patterns and chronic oral corticosteroid (≥28 days) use.Results: We identified 2,536 adults with asthma who initiated mepolizumab. There was an association toward reduction in severe asthma-related events over the first one year of exposure. We observed associations with reduced dispensings of oral corticosteroids over the first year after mepolizumab initiation. Very few patients switched to other biologics during the study period.Conclusions: Treatment with mepolizumab may be associated with fewer asthma-related events in the first year. Over the first one year after initiating mepolizumab, we found associations with decreased concomitant dispensings of oral corticosteroids and medium to high dose ICS/LABA. Additionally, most patients who initiated mepolizumab did not switch to other biologics.

Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

PURPOSE: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain. METHODS: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance. RESULTS: In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved). CONCLUSION: Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.

Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research.

BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS). METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS. RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million). CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.

Tick Paralysis Case Series: An 11-Year Institutional Case Series.

OBJECTIVES: The aims of the study were to identify and to describe cases of pediatric tick paralysis presenting to an emergency department in southern Louisiana during an 11-year period. METHODS: We conducted a retrospective chart review of patients aged 0 to 18 years with a diagnostic code of toxic effect of venom, tick-borne viral encephalitis, Guillain-Barré syndrome, acute infective polyneuritis, or abnormality of gait from July 2005 to June 2016. Data were collected on visit month, patient age, race and sex, tick's attachment site, location of tick removal, symptoms and length of symptoms, initial diagnosis, time to appropriate diagnosis, and hospital length of stay. RESULTS: Nine patients aged 2 to 10 years presented with lower limb weakness and varying degrees of upper extremity ataxia or paralysis, areflexia, dysarthria, diplopia, or petechia. Five cases were accurately and rapidly diagnosed; 4 cases involved a delay in accurate diagnosis. Treatment of the misdiagnosed cases ranged from septic workup to neurologic workup, including magnetic resonance imaging. The tick was discovered by the patients' relative in 4 cases, by a primary care or emergency care physician at another facility in 3 cases, and by 1 of our emergency care physicians in 2 patients. CONCLUSIONS: The incidence of tick paralysis in southern Louisiana is unknown. However, our case series indicates that it is likely higher than expected. Although most cases in our facility were quickly diagnosed and treated through tick removal, delayed diagnosis results in unnecessary tests, procedures, and medical costs. All of our cases fully recovered after tick removal.

Characteristics of new adult users of mepolizumab with asthma in the USA.

BACKGROUND: In the USA, over 25 million people have asthma; 5%-10% of cases are severe. Mepolizumab (Nucala) is an interleukin-5 antagonist monoclonal antibody; it was approved by the FDA in 2015 as add-on maintenance treatment of severe asthma for patients aged ≥12 years with an eosinophilic phenotype. OBJECTIVES: (1) Describe baseline demographic and clinical characteristics of new US adult mepolizumab users 2015-2019, (2) describe asthma medication use in the 12 months preceding initiation of and concomitant with mepolizumab and (3) assess mepolizumab adherence, persistence and discontinuation patterns in 12 months postinitiation. METHODS: We conducted a new-user observational cohort study using data from Aetna, a CVS Health Company, HealthCore (Anthem), Harvard Pilgrim Healthcare, and IBM MarketScan Research Databases. Curated administrative claims data in the FDA Sentinel System common data model format and publicly available Sentinel analytical tools were used to query the databases. We included adults who initiated mepolizumab in 2015-2019 with an asthma diagnosis in the preceding 12 months and no evidence of cystic fibrosis. We examined age, sex, comorbid conditions, asthma medication use and severe asthma exacerbations. RESULTS: We identified 3496 adults (mean age 54.2 years, SD 12.5 years) who initiated mepolizumab. In the 12 months before mepolizumab initiation, 22% had received inhaled corticosteroids, 46% had inhaled corticosteroid/long-acting beta agonists, 72.6% had leukotriene antagonists, 38% had long-acting muscarinic antagonist, 18% had omalizumab,<1% had reslizumab, dupilumab or benralizumab. In the previous 12 months, 70% had a diagnosis of allergic rhinitis, 32% had chronic obstructive pulmonary disease, 17% eosinophilia and 3% eosinophilic granulomatosis with polyangiitis. Further, 56% had an asthma-related ambulatory visit, 73%≥1 course of oral corticosteroids lasting 3-27 days, 10% an asthma-related emergency department visit and 22% an asthma-related hospitalisation. In the 12 months following initiation, the mean proportion of days covered was 70%, and reductions in the average mean dispensings of rescue oral corticosteriods (35%) and omalizumab (61%) were observed. CONCLUSIONS: Adults with asthma treated with mepolizumab had varying levels of healthcare utilisation and we observed evidence of mepolizumab use in patients without severe asthma.

Association of Alopecia Areata With Attention-Deficit/Hyperactivity Disorder Stimulant Medication: A Case-Control Study.

Background: Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of an association between attention-deficit/hyperactivity disorder (ADHD) stimulant medication (ASM) and various types of alopecia. Methods: We conducted a retrospective case-control medical record review of patients between the ages of 6 and 18 years seen in dermatology clinics during a 10-year period. Cases included patients diagnosed with alopecia areata (AA), alopecia totalis (AT), or alopecia universalis (AU). We matched 3 controls on age and sex to each case. We reviewed patients' medical records for the following medications: lisdexamfetamine, amphetamine/dextroamphetamine, dexmethylphenidate, and methylphenidate. We examined the association between medications used to treat ADHD and diagnoses of AA, AT, and/or AU by calculating a series of odds ratios and 95% CIs. Results: We identified 124 cases (110 with AA, 11 with AT, and 3 with AU) and 372 controls. We found a strong association between AU and ASM use (P<0.0071). No relationship between ASM use and other types of hair loss was found. Conclusion: Although the sample size of cases with AU was small, we found a significant association between AU and ASM. While further study is needed, practitioners may consider close monitoring of patients with AA who use ASM for the development of worsening disease and discontinue the medication if the patient experiences an increase in hair loss that appears to be progressing to AU.

Universal newborn genetic screening for pediatric cancer predisposition syndromes: model-based insights.

PURPOSE: Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs. METHODS: We developed a simulation model to evaluate universal screening for a CPS panel. Cohorts of US newborns were simulated under universal screening versus usual care. Using data from clinical studies, ClinVar, and gnomAD, the presence of pathogenic/likely pathogenic (P/LP) variants in RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, and PHOX2B were assigned at birth. Newborns with identified variants underwent guideline surveillance. Survival benefit was modeled via reductions in advanced disease, cancer deaths, and treatment-related late mortality, assuming 100% adherence. RESULTS: Among 3.7 million newborns, under usual care, 1,803 developed a CPS malignancy before age 20. With universal screening, 13.3% were identified at birth as at-risk due to P/LP variant detection and underwent surveillance, resulting in a 53.5% decrease in cancer deaths in P/LP heterozygotes and a 7.8% decrease among the entire cohort before age 20. Given a test cost of $55, universal screening cost $244,860 per life-year gained; with a $20 test, the cost fell to $99,430 per life-year gained. CONCLUSION: Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.

Using Multisource Feedback to Assess Resident Communication Skills: Adding a New Dimension to Milestone Data.

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires evaluation of residents' communication skills. These evaluations should involve assessments from a variety of persons with different perspectives and opportunities to observe resident behavior. Our objectives with this study were to determine if parents, nurses, and physicians significantly differed in their ratings of residents' communication skills; to ascertain the degree of association between these evaluations and ACGME milestone data; and to elicit feedback from residents about the specificity and usefulness of this type of evaluation compared to the evaluations they were typically provided. Methods: During the 2016-2017 academic year, parents of patients ready for discharge, nurses, and attending physicians completed evaluations of resident communication skills. A repeated measures multivariate analysis of variance compared communication skills scores across the 3 groups of raters. Resident ACGME milestone ratings for interpersonal and communication skills were correlated with the communication skills evaluations. Residents rated the specificity and usefulness of the 360-degree evaluations. Results: Parents rated residents' communication skills significantly higher than nurses and physicians rated them. We found no significant difference between the nurse and physician ratings. A significant correlation was found between resident ratings by physicians and ACGME milestone data. Residents found the feedback from these evaluations to be more specific and useful in delineating their communication strengths and weaknesses than typical milestone feedback. Conclusion: Parents added a unique perspective about residents' communication and should be included in resident evaluation when feasible. Residents appreciated the specificity and usefulness of the evaluation instrument.

Practitioner Engagement in Activities of the National Dental Practice-Based Research Network (PBRN): 7-Year Results.

PURPOSE: To 1) quantify practitioner activities of the National Dental Practice-Based Research Network (Network) for which Continuing Education (CE) credits were received (study training, videos, webinars, meetings, and symposia); 2) quantify practitioner coauthoring Network publications and presentations; and 3) test whether practitioner characteristics were associated with participation in these activities. METHODS: A retrospective analysis of 4361 practitioners who enrolled in the Network between April 12, 2012 and October 12, 2018. RESULTS: Overall, 59% (n = 2586) of practitioners earned CE credit from the Network; among these, 68% (n = 1757) from a video, 38% (n = 993) attended an annual Network meeting, 31% (n = 798) due to training for a Network clinical study, 9% (n = 226) attended a national symposium, and 7% (n = 170) participated in a Network webinar. Members of 2 large group practices earned on average more CEs than practitioners from other practice settings. Four percent (n = 159) of practitioners coauthored a Network presentation or publication. Practitioners who received their dental degree before 2000, were general practitioners, or were members of 2 large group practices, were more likely to have coauthored a publication or presentation. CONCLUSION: This Network used a broad range of activities to engage community practitioners. These activities were successful in sustaining a high level of practitioner engagement in clinical research and its relevance to everyday clinical practice.

The Relationship Between Grit and Resilience in Emergency Medical Service Personnel.

Background: Emergency medical service (EMS) personnel are regularly exposed to traumatic incidents and experience higher rates of symptoms of posttraumatic stress disorder (PTSD) than the general population. Grit is a construct proposed to be associated with achievement, but it has demonstrated preliminary evidence of an association with resilience. The current study examined the relationship between grit and resilience among EMS workers. Methods: A link to an online survey was sent to East Baton Rouge Parish Emergency Medical Services personnel via an email distribution list. Demographic variables and the following self-report measures were assessed: the PTSD Checklist for DSM-5 (PCL-5), the Grit Scale, the Brief COPE scale, and the Professional Exposure to Traumatic Experiences scale (modified from the Life Events Checklist). Results: PCL-5 scores were significantly and negatively correlated with the Grit Scale score (r=-0.57, P<0.01). Hierarchical regression revealed that grit and coping mechanisms were predictive of self-reported PTSD symptoms (adjusted R2=68.7%, F(15,67)=9.81, P<0.001). Examination of the coefficients revealed that lower total Grit Scale scores and higher scores on the following Brief COPE scales were significant predictors of PCL-5 scores: denial, substance abuse, disengagement, and self-blame. Conclusion: This study examined the relationship between grit and resilience, measured by self-reported PTSD symptoms. Our results demonstrate a significant relationship between grit and resilience. Grit is related to, but distinct from, other constructs that predict resilience, such as coping mechanisms. Large prospective studies could have significant implications for hiring practices and building grit in existing personnel to bolster resilience.

Parent and Child Reports of Food Insecurity and Mental Health: Divergent Perspectives.

BACKGROUND: Food insecurity-the inability to provide adequate food for at least one household member sometime during the year-is linked to negative physical and mental health outcomes. Child reports of experiences in other domains of life are only moderately related to parental proxy reports of the same experiences. The goal of our study was to assess the convergence of parent and child reports of food insecurity and several specific mental health symptoms. METHODS: Dyads of parents and children attending medical appointments were surveyed. Inclusion criteria consisted of English-speaking adults and their children between the ages of 8 and 17 years. RESULTS: Sixty-two percent of adults and 50% of children self-reported meeting screening criteria for food insecurity, and adult-child dyad reports were significantly correlated. However, when asked about the child worrying about food running out or having eaten less than desired in order to conserve food, adult and child reports diverged significantly, with adults more frequently underestimating worry and conservation behaviors compared to child self-reports. Similar discrepancies were found for items probing specific symptoms of depression, general anxiety, and obsessive-compulsive disorder. CONCLUSION: Our data show that adults may not accurately perceive the subjective effects of food insecurity on children in their household, particularly in households receiving food assistance, perhaps because of objectively greater need. Because food insecurity may have profound effects on child development, pediatricians should be aware of the mental health risks for children in food-insecure homes.

Practitioner Participation in National Dental Practice-based Research Network (PBRN) Studies: 12-Year Results.

PURPOSE: This study examines practitioner participation over 12 years in the National Dental Practice-Based Research Network (PBRN) studies and practitioner meetings, average length of participation, and association of practitioner- and practice-level characteristics with participation. Little information exists about practitioners' long-term participation in PBRNs. METHODS: The network conducted a retrospective analysis of practitioner participation in 3 main network activities during 2005 to 2017. Practitioners who completed an enrollment questionnaire, practiced in the United States, and either attended a network meeting or received an invitation to complete a questionnaire or clinical study were included in the analysis. Practitioners (n = 3669) met inclusion criteria. The network implemented 38 studies (28 clinical and 10 questionnaire), 23 of which (15 clinical and 8 questionnaire) met the criteria for the current analysis. RESULTS: Overall, 86% (N = 3148) participated in at least 1 network activity during 2005 to 2017. Questionnaire studies had the highest rate with 81% (N = 2963) completing at least 1, 21% (N = 762) completed at least 1 clinical study and 19% (N = 700) attended at least 1 network meeting. Among 1578 practitioners enrolled in the first 5 years of the Network launch, 20% (N = 320) participated in multiple network activities over 5 to 9 years, and 14% (N = 238) for 10 to 12 years. Practitioner characteristics associated with participation varied depending on the activity assessed. CONCLUSION: The network engaged practitioners in its research activities with relatively high participation rates over a 12-year period. Strategies employed by the network to engage practitioners may serve as a model for PBRN networks for other allied health professions.

An Atypical Case of Bartonella henselae Osteomyelitis and Hepatic Disease.

Bartonella henselae is a Gram-negative bacterium and the causative agent of cat scratch disease (CSD). Atypical presentations of B. henselae that involve the musculoskeletal, hepatosplenic, cardiac, or neurologic systems are rare. In this case report, we describe a case of B. henselae osteomyelitis involving bilateral iliac bones complicated by hepatic lesions in a 12-year-old immunocompetent female patient. Although B. henselae is a rare cause of osteomyelitis, it should be considered when patients who present with fever, pain, and lymphadenopathy do not respond to routine osteomyelitis therapy.

Integration of Mobile Devices to Facilitate Patient Care and Teaching During Family-Centered Rounds.

OBJECTIVES: The increasing prevalence of mobile devices in clinical settings has the potential to improve both patient care and education. The benefits are particularly promising in the context of family-centered rounds in inpatient pediatric settings. We aimed to increase mobile device usage by inpatient rounding teams by 50% in 6 months. We hoped to demonstrate that use of mobile devices would improve access to patient care and educational information and to determine if use would improve efficiency and perceptions of clinical teaching. METHODS: We designed a mixed-methods study involving pre- and post-implementation surveys to residents, families, and faculty as well as direct observations of family-centered rounds. We conducted rapid cycles of continual quality improvement by using the Plan-Do-Study-Act framework involving 3 interventions. RESULTS: Pre-intervention, the mobile computing cart was used for resident education on average 3.3 times per rounding session. After cycle 3, teaching through the use of mobile devices increased by ∼79% to 5.9 times per rounding session. On the basis of survey data, we determined there was a statistically significant increase in residents' perception of feeling prepared for rounds, receiving teaching on clinical care, and ability to teach families. Additionally, average time spent per patient on rounds decreased after implementation of mobile devices. CONCLUSIONS: Integration of mobile devices into a pediatric hospital medicine teaching service can facilitate patient care and perception of resident teaching by extending the utility of electronic medical records in care decisions and by improving access to knowledge resources.

The impact of overdiagnosis on the selection of efficient lung cancer screening strategies.

The U.S. Preventive Services Task Force (USPSTF) recently updated their national lung screening guidelines and recommended low-dose computed tomography (LDCT) for lung cancer (LC) screening through age 80. However, the risk of overdiagnosis among older populations is a concern. Using four comparative models from the Cancer Intervention and Surveillance Modeling Network, we evaluate the overdiagnosis of the screening program recommended by USPSTF in the U.S. 1950 birth cohort. We estimate the number of LC deaths averted by screening (D) per overdiagnosed case (O), yielding the ratio D/O, to quantify the trade-off between the harms and benefits of LDCT. We analyze 576 hypothetical screening strategies that vary by age, smoking, and screening frequency and evaluate efficient screening strategies that maximize the D/O ratio and other metrics including D and life-years gained (LYG) per overdiagnosed case. The estimated D/O ratio for the USPSTF screening program is 2.85 (model range: 1.5-4.5) in the 1950 birth cohort, implying LDCT can prevent ∼3 LC deaths per overdiagnosed case. This D/O ratio increases by 22% when the program stops screening at an earlier age 75 instead of 80. Efficiency frontier analysis shows that while the most efficient screening strategies that maximize the mortality reduction (D) irrespective of overdiagnosis screen through age 80, screening strategies that stop at age 75 versus 80 produce greater efficiency in increasing life-years gained per overdiagnosed case. Given the risk of overdiagnosis with LC screening, the stopping age of screening merits further consideration when balancing benefits and harms.

Cost Analysis of a Randomized Trial of Early Palliative Care in Patients with Metastatic Nonsmall-Cell Lung Cancer.

BACKGROUND: Several trials have shown that integrated palliative and oncology care improves quality of life and mood in patients with advanced cancers. However, the degree to which early involvement of palliative care (PC) in the outpatient setting impacts the cost of care remains unknown. METHODS: Data for this secondary analysis came from a trial of 151 patients with metastatic nonsmall-cell lung cancer (NSCLC) who were randomized to early PC integrated with standard oncology care (SC) or SC alone. We abstracted costs for hospital and outpatient care, including intravenous chemotherapy, from the hospital accounting system. Oral chemotherapy costs were estimated based on actual drug costs. To estimate hospice costs, we used Medicare reimbursement rates. We examined between-group differences in costs of care throughout the entire study period and during the last 30 days before death using the bootstrap-t method. RESULTS: The analytic sample includes the 138/151 patients who died by July 15, 2013. Early PC was associated with a lower mean total cost per day of $117 (p = 0.13) compared to SC. In the final 30 days of life, patients in the early PC group incurred higher hospice care costs (mean difference = $1,053; p = 0.07), while expenses for chemotherapy were less (mean difference = $757; p = 0.03). Costs for emergency department visits and hospitalizations did not differ significantly between groups over the course of the study or at the end of life. CONCLUSIONS: The delivery of early PC does not appear to increase overall medical care expenses for patients with metastatic NSCLC. Larger, sufficiently powered cost studies of early PC are needed.