Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data.

BACKGROUND: The 10 Warning Signs of Primary Immunodeficiency were created 30 years ago to advance recognition of inborn errors of immunity (IEI). However, no population-level assessment of their utility applied to electronic health record (EHR) data has been conducted. OBJECTIVE: We sought to quantify the value of having ≥2 warning signs (WS) toward diagnosing IEI using a highly representative real-world US cohort. A secondary goal was estimating the US prevalence of IEI. METHODS: In this cohort study, we accessed normalized and de-identified EHR data on 152 million US patients. An IEI cohort (n = 41,080), in which patients were defined by having at least 1 verifiable IEI diagnosis placed ≥2 times in their record, was compared with a matched set of controls (n = 250,262). WS were encoded along with relevant diagnoses, relative weights were calculated, and the proportion of IEI cases versus controls with ≥2 WS was compared. RESULTS: The proportion of IEI cases with ≥2 WS significantly differed from controls (0.33 vs 0.031; P < .0005, χ2 test). We also estimated a US IEI prevalence of 6 per 10,000 individuals (41,080/73,165,655; 0.056%). WS 9 (≥2 deep-seated infections), 7 (fungal infections), 5 (failure to thrive) and 4 (≥2 pneumonias in 1 year) were the most heavily weighted among the IEI cohort. CONCLUSIONS: This nationally representative US-based cohort study demonstrates that presence of WS and associated clinical diagnoses can facilitate identification of patients with IEI from EHR data. In addition, we estimate that 6 in 10,000, or approximately 150,000 to 200,000 individuals are affected by IEI across the United States.

A validated artificial intelligence-based pipeline for population-wide primary immunodeficiency screening.

BACKGROUND: Identification of patients with underlying inborn errors of immunity and inherent susceptibility to infection remains challenging. The ensuing protracted diagnostic odyssey for such patients often results in greater morbidity and suboptimal outcomes, underscoring a need to develop systematic methods for improving diagnostic rates. OBJECTIVE: The principal aim of this study is to build and validate a generalizable analytical pipeline for population-wide detection of infection susceptibility and risk of primary immunodeficiency. METHODS: This prospective, longitudinal cohort study coupled weighted rules with a machine learning classifier for risk stratification. Claims data were analyzed from a diverse population (n = 427,110) iteratively over 30 months. Cohort outcomes were enumerated for new diagnoses, hospitalizations, and acute care visits. This study followed TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) standards. RESULTS: Cohort members initially identified as high risk were proportionally more likely to receive a diagnosis of primary immunodeficiency compared to those at low-medium risk or those without claims of interest respectively (9% vs 1.5% vs 0.2%; P < .001, chi-square test). Subsequent machine learning stratification enabled an annualized individual snapshot of complexity for triaging referrals. This study's top-performing machine learning model for visit-level prediction used a single dense layer neural network architecture (area under the receiver-operator characteristic curve = 0.98; F1 score = 0.98). CONCLUSIONS: A 2-step analytical pipeline can facilitate identification of individuals with primary immunodeficiency and accurately quantify clinical risk.

Needs assessment of cancer survivors in Alaska.

PURPOSE: Little is known about cancer survivors' needs in Alaska. To address this knowledge gap, the Alaska Cancer Partnership conducted a needs assessment survey; our objectives were to identify unmet needs of Alaska's cancer survivors; identify survivor sub-populations that might benefit from targeted interventions or programming; and develop recommendations for public health and community organizations and healthcare providers for addressing cancer survivors' unmet needs. METHODS: Cancer survivors were identified using data from the Alaska Cancer Registry. A random sample of 2,600 individuals was selected to receive the survey, which assessed unmet needs across the following domains: information needs and medical care issues; quality of life; emotional and relationship issues related to cancer diagnoses; and support services. We calculated descriptive statistics for survey responses and assessed demographic predictors of unmet needs using Poisson regression. RESULTS: We received 335 survey responses, for a response of 13.7%. Only 29.9% of cancer survivors expressed that all their needs were met. The most highly ranked unmet needs were as follows: help to reduce stress in life; to know doctors were coordinating care; and managing concerns about cancer coming back. After adjustment, men, adults younger than 65 at diagnosis, Alaska Native people, survivors still receiving or who had recently received care, and people who had to travel 50+ miles for most of their care had significantly greater unmet needs than their comparison groups. CONCLUSION: This assessment provided some of the first information regarding the needs of Alaska's cancer survivors. These results will be used by Alaska Cancer Partnership members across the state to inform healthcare delivery, programs, and public health messaging to support survivors.

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity.

BACKGROUND: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. METHODS: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. RESULTS: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). CONCLUSIONS: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.

Long-term change in the parasite burden of shore crabs (Hemigrapsus oregonensis and Hemigrapsus nudus) on the northwestern Pacific coast of North America.

The abundances of free-living species have changed dramatically in recent decades, but little is known about change in the abundance of parasitic species. We investigated whether populations of several parasites have shifted over time in two shore crab hosts, Hemigrapsus oregonensis and Hemigrapsus nudus, by comparing the prevalence and abundance of three parasite taxa in a historical dataset (1969-1970) to contemporary parasite abundance (2018-2020) for hosts collected from 11 intertidal sites located from Oregon, USA, to British Columbia, Canada. Our data suggest that the abundance of the parasitic isopod Portunion conformis has varied around a stable mean for the past 50 years. No change over time was observed for larval acanthocephalans. However, larval microphallid trematodes increased in prevalence over time among H. oregonensis hosts, from a mean of 8.4-61.8% between the historical and contemporary time points. The substantial increase in the prevalence of larval microphallid trematodes could be owing to increased abundances of their bird final hosts, increased production of parasite infective stages by snail intermediate hosts or both. Our study highlights the variability among parasite species in their temporal trajectories of change.

Clinical trial discussion, referral, and recruitment: physician, patient, and system factors.

PURPOSE: Patient participation in cancer clinical trials is imperative to the advancement of medical science. Physicians play an important role in recruitment by discussing clinical trials with their cancer patients. Patient-physician discussion is influenced by many factors relating to the physician, the patient, and the healthcare system. METHODS: Physicians selected from the 2008-2009 American Medical Association Physician Masterfile who practiced in California, Florida, Illinois, or New York and specialized in medical oncology, surgery, or radiation oncology were surveyed about their attitudes and practices with respect to breast cancer clinical trials. Practice types were categorized according to the classifications provided by the American College of Surgeons, and clinical trial and practice addresses were geocoded. RESULTS: Surveys were completed by 706 of 1,534 eligible physicians (46 %). Medical oncologists were more likely than surgical or radiation oncologists to discuss the possibility, benefits, and risks of clinical trial enrollment with their breast cancer patients. Physicians who spent the most time in patient care were least likely to discuss clinical trials with their patients. Distance from a physician's practice to the nearest clinical trial site was inversely associated with referral and recruitment. Perceived barriers to clinical trial participation were associated with greater referral activity suggesting that physicians who were more involved in trials were also more likely to understand barriers to participation. CONCLUSIONS: Multilevel interventions may be successful at increasing participation of women in clinical trials.

Growth in diagnosis and treatment of primary immunodeficiency within the global Jeffrey Modell Centers Network.

BACKGROUND: Primary immunodeficiencies (PI), which include more than 450 single-gene inborn errors of immunity and may affect up to 1% of the population, are genetic disorders that impair the immune system. If not properly identified and treated, individuals with PI are subject to serious, prolonged, and sometimes life-threatening infections or autoimmunity. Despite advancements, awareness of PI remains a critical issue for physicians and the public alike, as this leads to the enhanced and expedited management of these conditions. To address this critical issue, the Jeffrey Modell Foundation (JMF) formed a global network of specialized centers. The goal of this endeavor was to raise awareness of PI to better identify, diagnose, and treat patients, reducing associated mortality and morbidity and improving quality of life (QOL). For more than two decades, the Jeffrey Modell Centers Network (JMCN) has served as the foundation upon which these goals have been pursued. The JMCN currently includes 909 Expert Physicians at 400 institutions, in 316 cities, and 86 countries spanning six continents. METHODS: A survey was developed by JMF for members of the JMCN, following the most recent Classification of PI from the IUIS Expert Committee, to periodically describe the patient population, including treatment modalities and demographics. Physician-reported data from 2021 was compared to that from 2018 and 2013. Physicians in the JMCN also reported on select outcomes of their PI patients one year prior to and one year following diagnosis. RESULTS: A total of 300 JMF Physician Surveys from 681 physicians were included in this analysis. This is a 75% physician response rate. From 2013 to 2021, there was a 96.3% increase in patients followed in the US and an 86.1% increase globally. During the same period, patients identified with a specific PI defect increased by 46.6% in the US and 47.9% globally. Patients receiving IgG and HSCT increased by 110% and 201% respectfully since 2013. Early diagnosis led to reported decreased morbidity and mortality and reduced calculated healthcare costs. CONCLUSIONS: This global analysis of physician-reported data on patients with PI demonstrates an increase in both diagnosed and treated patients. This substantial increase from within the JMCN is a testament to its impact. In addition to building an extensive global patient database, the expanding JMCN serves as a unique and critical resource, providing the infrastructure for earliest diagnosis, optimized treatments, and implementation of standard-of-care and best practices. The JMCN provides a critical platform that facilitates the education of physicians and patients, awareness initiatives, and research advances, through collaboration and connectivity, ultimately resulting in improved outcomes and QOL for patients with PI. The JMCN has steadily and substantially grown for more than two decades and continues to substantively impact the field of Immunology globally.

Global Expansion of Jeffrey's Insights: Jeffrey Modell Foundation's Genetic Sequencing Program for Primary Immunodeficiency.

Genetic disorders that impair the immune system, known as Primary Immunodeficiencies (PI), include over 450 single-gene inborn errors of immunity. Timely and appropriate diagnosis and treatment is vital to quality of life (QOL) and sometimes survival, as patients are susceptible to frequent, persistent, severe, and sometimes life-threatening infections or autoimmunity. Suspected PI patients that do not have a genetic diagnosis often endure a prolonged, onerous, inefficient, and expensive experience, known as a diagnostic odyssey. The resulting diagnostic delay prohibits proper disease management and treatment, causing unnecessary distress and diminished QOL. Next-generation sequencing (NGS) offers relief from the distress of the diagnostic odyssey, but because of cost and barriers to access, it is regularly unobtainable. The Jeffrey Modell Foundation (JMF) introduced "Jeffrey's Insights", a no-charge genetic sequencing pilot program, in January 2019 for patients within the Jeffrey Modell Centers Network (JMCN) with an underlying PI, but no genetic diagnosis. Building on the success of the pilot program, JMF expanded it globally to more than 400 Centers in the JMCN in early 2020. The most current version of Invitae's PI Panel available was used for this program. All participating clinicians were invited to complete a brief questionnaire assessing prior impediments to access and post-sequencing alterations in disease management and treatment. A total of 1,398 patients were tested, with 20.3% receiving a molecular diagnosis and many more receiving helpful diagnostic leads. Results obtained from genetic sequencing led to an alteration of clinical diagnosis, disease management, treatment, and genetic counseling in 39%, 38%, 35%, and 53% of patients, respectively. The global expansion of this program further underscores the crucial need for NGS for PI, along with its efficiency and potential cost savings. The results of this program to date further define rationale for the availability of comprehensive diagnostic NGS for patients with PI when requisitioned by an expert immunologist.

The effect of system-level access factors on receipt of reconstruction among Latina and white women with DCIS.

Treatment decisions associated with ductal carcinoma in situ (DCIS), including the decision to undergo breast reconstruction, may be more problematic for Latinas due to access and language issues. To help understand the factors that influence patients' receipt of reconstruction following mastectomy for DCIS, we conducted a population-based study of English- and Spanish-speaking Latina and non-Latina white women from 35 California counties. The objectives of this study were to identify the role of ethnicity and language in the receipt of reconstruction, the relationship between system-level factors and the receipt of reconstruction, and women's reasons for not undergoing reconstruction. Women aged 18 and older, who self-identified as Latina or non-Latino white and were diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions encompassing 35 counties. Approximately 24 months after diagnosis, they were surveyed about their DCIS treatment decisions. Survey data were merged with CCR records to obtain tumor and treatment data. The survey was successfully completed by 745 women, 239 of whom had a mastectomy and represent the sample included in this study. Whites had a higher completion rate than Latinas (67 and 55%, respectively). Analysis included descriptive statistics and logistic regression modeling. Mean age was 54 years. A greater proportion of whites had reconstruction (72%) compared to English-speaking Latinas (69%) and Spanish-speaking Latinas (40%). Multivariate analysis showed that women who were aged 65 and older, unemployed, and had a lower ratio of plastic surgeons in their county were less likely to have reconstructive surgery after mastectomy. The most frequent reasons mentioned not to receive reconstruction included lack of importance and desire to avoid additional surgery. Although ethnic/language differences in treatment selection were observed, multivariable analysis suggests that these differences could be explained by differential employment levels and geographic availability of plastic surgeons.

Complication associated with abdominal surgical implantation of a radio transmitter in an American badger (Taxidea taxus).

Radio telemetry has greatly advanced the understanding of wild animal ecology. Telemetry studies must ensure that placement of transmitters does not influence the health and behavior of study animals. Here, 10 American badgers (Taxidea taxus) were implanted with beeswax-coated abdominal radio transmitters under general anesthesia and tracked for an average of 14 mo. Behavior and movements of all badgers indicated successful short-term recovery from implantation; however, three mortalities were observed between 5 mo and 15 mo after capture. Cause of death could not be determined for two badgers due to decomposition of the carcasses. A third badger that was recovered in good postmortem condition died from sepsis secondary to a transmitter-related omental torsion. This study indicates that there is some risk associated with abdominally implanted radio transmitters in badgers. Future studies involving implanted transmitters in mammals should focus on identifying safe and effective telemetry devices that do not affect the health of study animals. American badger, omental adhesion, peritoneal implant, telemetry, Taxidea taxus.

The case for severe combined immunodeficiency (SCID) and T cell lymphopenia newborn screening: saving lives one at a time.

Severe combined immunodeficiency (SCID) is a group of syndromes resulting from genetic defects causing severe deficiency in T cell and B cell function. These conditions are life-threatening and result in susceptibility to serious infections. SCID is often fatal in the first year of life if not detected and properly treated. SCID and related T cell lymphopenias can be detected in newborns by a simple screening test, the T cell receptor excision circle (TREC) assay, using the same dried blood spot samples already collected from newborns to screen for other genetic disorders. The TREC assay facilitates the earliest possible identification of cases of SCID before opportunistic infections, irreversible organ damage, or death, thus allowing for the possibility of curative treatment through hematopoietic stem cell transplant and gene therapy. Infants receiving hematopoietic stem cell transplant in the first few months of life, after being identified through screening, have a high probability of survival (95-100%), along with lower morbidity. The TREC assay has proven to have outstanding specificity and sensitivity to accurately identify almost all infants with SCID (the primary targets) as well as additional infants having other select immunologic abnormalities (secondary targets). The TREC assay is inexpensive and has been effectively integrated into many public health programs. Without timely treatment, SCID is a fatal disease that causes accrual of exorbitant healthcare costs even in just 1 year of life. The cost of care for just one infant with SCID, not diagnosed through newborn screening, could be more than the cost of screening for an entire state or regional population. Continued implementation of TREC screening will undoubtedly enhance early diagnosis, application of treatment, and healthcare cost savings. The Jeffrey Modell Foundation helped initiate newborn screening for SCID in the USA in 2008 and continues its efforts to advocate for SCID screening worldwide. Today, all 50 states and Puerto Rico are screening for SCID and T cell lymphopenia, with 27 million newborns screened to date, and hundreds diagnosed and treated. Additionally, there are at least 20 countries around the world currently conducting screening for SCID at various stages. Newborn screening for SCID and related T cell lymphopenia is cost-effective, and most importantly, it is lifesaving and allows children with SCID the opportunity to live a healthy life.

Jeffrey's insights: Jeffrey Modell Foundation's global genetic sequencing pilot program to identify specific primary immunodeficiency defects to optimize disease management and treatment.

Primary immunodeficiencies (PI) are genetic defects of the immune system that result in chronic and often life-threatening infections and/or life-threatening autoimmunity if not diagnosed and treated. Patients with a suspected PI, but without a genetic diagnosis, commonly undergo a diagnostic odyssey that is costly, time-consuming, and arduous. This delay in diagnosis prevents appropriate disease management and treatment, contributing to prolonged suffering and decreased quality of life. Although next generation sequencing (NGS) can provide these patients with relief from such a diagnostic odyssey, it is often unavailable, mainly due to cost and inaccessibility. In January 2019, the Jeffrey Modell Foundation (JMF) launched a free genetic sequencing pilot program for Jeffrey Modell Centers Network (JMCN) patients clinically diagnosed with an underlying PI. A total of 21 sites within the JMCN were invited to participate. JMF collaborated with Invitae, and testing was comprised of Invitae's Primary Immunodeficiency Panel, which currently includes 207 genes. A questionnaire was disseminated to each participating physician to evaluate barriers to access to genetic sequencing and changes in disease management and treatment after testing. One hundred fifty-eight patients and 29 family members were tested in this pilot study. Twenty-one percent of patients with a suspected monogenic disorder received a molecular diagnosis, and others received potentially useful diagnostic leads. Based on the results of genetic sequencing, clinical diagnosis was altered in 45% of patients, disease management was altered in 40%, treatment was altered in 36%, and genetic counseling was altered in 62%. The results of this pilot program demonstrate the utility, cost-efficiency, and critical importance of NGS for PI and make the case for broad scale sequence-based diagnostics for PI patients when requested by expert immunologists.

Global systematic review of primary immunodeficiency registries.

INTRODUCTION: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. AREAS COVERED: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. EXPERT OPINION: Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.

Calculation of a Primary Immunodeficiency "Risk Vital Sign" via Population-Wide Analysis of Claims Data to Aid in Clinical Decision Support.

Background: Early diagnosis of primary immunodeficiency disease leads to reductions in illness and decreased healthcare costs. Analysis of electronic health record data may allow for identification of persons at risk of host-defense impairments from within the general population. Our hypothesis was that coded infection history would inform individual risk of disease and ultimately lead to diagnosis. Methods: In this study we assessed individual risk for primary immunodeficiency by analyzing diagnostic codes and pharmacy records from members (n = 185,892) of a large pediatric health network. Relevant infection-associated diagnostic codes were weighted and enumerated for individual members allowing for risk score calculations ("Risk Vital Sign"). At-risk individuals underwent further assessment by chart review and re-analysis of diagnostic codes 12 months later. Results: Of the original cohort, 2188 (1.2%) individuals were identified as medium-high-risk for having a primary immunodeficiency. This group included 41 subjects who were ultimately diagnosed with primary immunodeficiency. An additional 57 medium-high risk patients had coded diagnoses worthy of referral. Conclusions: Population-wide informatics approaches can facilitate disease detection and improve outcomes. Early identification of the 98 patients with confirmed or suspected primary immunodeficiency described here could represent an annual cost savings of up to $7.7 million US Dollars.

Improving Response Rates and Representation of Hard-to-Reach Groups in Family Experience Surveys.

OBJECTIVE: Most US hospitals conduct patient experience surveys by mail or telephone after discharge to assess patient/family centeredness of care. Pediatric response rates are usually very low, especially for black, Latino, and low-income respondents. We investigated whether day of discharge surveying using tablets improves response rates and respondent representativeness. METHODS: This was a quasi-experimental study of parents of patients discharged from 4 units of a children's hospital. Parents were assigned to receive the Child Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) via an audio-enabled tablet before discharge or via mail at approximately 1 week postdischarge. Intervention and control conditions alternated by week. We compared response rates, child/respondent characteristics, and mean top-box scores between tablet and mail only arms. RESULTS: Administering Child HCAHPS on a tablet was administratively feasible and did not interfere with the discharge process (median completion time, 12.4 minutes). The response rate was 71.1% (424 of 596) for tablet versus 16.3% (96 of 588) for mail only. Although the tablet response rate was higher in every subgroup, tablet respondents were more likely to be fathers (20.4% vs 6.4%; P = .006), more likely to have a high school education or less (17.5% vs 8.4%; P = .002), less likely to be white (56.8% vs 71.9%; P = .006), and more likely to be publicly insured (31.4% vs 19.8%; P = .02). Tablet scores were significantly higher than mail only scores for 3 of 17 measures. CONCLUSIONS: The response rate for day of discharge tablet survey administration was >4-fold higher than with single-wave mail-only administration, with greater participation of hard-to-reach groups. These findings suggest tablet administration before discharge shows great promise for real-time feedback and QI and may transform the field of inpatient survey administration.

Care Quality and Spending Among Commercially Insured Children With Disabilities.

OBJECTIVE: To identify opportunities to improve care value for children with disabilities (CWD), we examined CWD prevalence within a commercially insured population and compared outpatient care quality and annual health plan spending levels for CWD relative to children with complex medical conditions without disabilities; children with chronic conditions that are not complex; and children without disabling, complex, or chronic conditions. METHODS: This cross-sectional study comprised 1,118,081 person-years of Blue Cross Blue Shield Massachusetts data for beneficiaries aged 1 to 19years old during 2008 to 2012. We combined the newly developed and validated Children with Disabilities Algorithm with the Pediatric Medical Complexity Algorithm to identify CWD and non-CWD subgroups. We used 14 validated or National Quality Forum-endorsed measures to assess outpatient care quality and paid claims to examine annual plan spending levels and components. RESULTS: CWD constituted 4.5% of all enrollees. Care quality for CWD was between 11% and 59% for 8 of 14 quality measures and >80% for the 6 remaining measures and was generally comparable to that for non-CWD subgroups. Annual plan spending among CWD was a median and mean 23% and 53% higher than that for children with complex medical conditions without disabilities, respectively; CWD mean and median values were higher than for all other groups as well. CONCLUSIONS: CWD were prevalent in our commercially insured population. CWD experienced suboptimal levels of care, but those levels were comparable to non-CWD groups. Improving the care value for CWD involves a deeper understanding of what higher spending delivers and additional aspects of care quality.

Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes.

Primary immunodeficiencies (PI) are genetic defects of the immune system that result in chronic, serious, and often life-threatening infections, if not diagnosed and treated. Many patients with PI are undiagnosed, underdiagnosed, or misdiagnosed. In fact, recent studies have shown that PI may be more common than previously estimated and that as many as 1% of the population may be affected with a PI when all types and varieties are considered. In order to raise awareness of PI with the overall goal of reducing associated morbidity and mortality, the Jeffrey Modell Foundation (JMF) established a network of specialized centers that could better identify, diagnose, treat, and follow patients with PI disorders. Over the past decade, the Jeffrey Modell Centers Network (JMCN) has provided the infrastructure to accept referrals, provide diagnosis, and offer treatments. Currently, the network consists of 792 Expert Physicians at 358 institutions, in 277 cities, and 86 countries spanning 6 continents. JMF developed an annual survey for physician experts within the JMCN, using the categories and gene defects identified by the International Union of Immunological Societies Expert Committee for the Classification of PI, to report on the number of patients identified with PI; treatment modalities, including immunoglobulins, transplantation, and gene therapy; and data on gender and age. Center Directors also provided physician-reported outcomes and differentials pre- and post-diagnosis. The current physician-reported data reflect an increase in diagnosed patients, as well as those receiving treatment. Suspected patients are being identified and referred so that they can receive early and appropriate diagnosis and treatment. The significant increase in patients identified with a PI is due, in part, to expanding education and awareness initiatives, newborn screening, and the expansion of molecular diagnosis and sequencing. To our knowledge, this is the most extensive single physician report on patients with PI around the world.

Adverse Events in Hospitalized Pediatric Patients.

: media-1vid110.1542/5789657761001PEDS-VA_2017-3360Video Abstract BACKGROUND: Patient safety concerns over the past 2 decades have prompted widespread efforts to reduce adverse events (AEs). It is unclear whether these efforts have resulted in reductions in hospital-wide AE rates. We used a validated safety surveillance tool, the Global Assessment of Pediatric Patient Safety, to measure temporal trends (2007-2012) in AE rates among hospitalized children. METHODS: We conducted a retrospective surveillance study of randomly selected pediatric inpatient records from 16 teaching and nonteaching hospitals. We constructed Poisson regression models with hospital random intercepts, controlling for patient age, sex, insurance, and chronic conditions, to estimate changes in AE rates over time. RESULTS: Examining 3790 records, reviewers identified 414 AEs (19.1 AEs per 1000 patient days; 95% confidence interval [CI] 17.2-20.9) and 210 preventable AEs (9.5 AEs per 1000 patient days; 95% CI 8.2-10.8). On average, teaching hospitals had higher AE rates than nonteaching hospitals (26.2 [95% CI 23.7-29.0] vs 5.1 [95% CI 3.7-7.1] AEs per 1000 patient days, P < .001). Chronically ill children had higher AE rates than patients without chronic conditions (33.9 [95% CI 24.5-47.0] vs 14.0 [95% CI 11.8-16.5] AEs per 1000 patient days, P < .001). Multivariate analyses revealed no significant changes in AE rates over time. When stratified by hospital type, neither teaching nor nonteaching hospitals experienced significant temporal AE rate variations. CONCLUSIONS: AE rates in pediatric inpatients are high and did not improve from 2007 to 2012. Pediatric AE rates were substantially higher in teaching hospitals as well as in patients with more chronic conditions.

Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement.

This study seeks to generate analytic insights into risk management and probability of an identifiable primary immunodeficiency defect. The Jeffrey Modell Centers Network database, Jeffrey Modell Foundation's 10 Warning Signs, the 4 Stages of Testing Algorithm, physician-reported clinical outcomes, programs of physician education and public awareness, the SPIRIT® Analyzer, and newborn screening, taken together, generates P values of less than 0.05%. This indicates that the data results do not occur by chance, and that there is a better than 95% probability that the data are valid. The objectives are to improve patients' quality of life, while generating significant reduction of costs. The advances of the world's experts aligned with these JMF programs can generate analytic insights as to risk management and probability of an identifiable primary immunodeficiency defect. This strategy reduces the uncertainties related to primary immunodeficiency risks, as we can screen, test, identify, and treat undiagnosed patients. We can also address regional differences and prevalence, age, gender, treatment modalities, and sites of care, as well as economic benefits. These tools support high net benefits, substantial financial savings, and significant reduction of costs. All stakeholders, including patients, clinicians, pharmaceutical companies, third party payers, and government healthcare agencies, must address the earliest possible precise diagnosis, appropriate intervention and treatment, as well as stringent control of healthcare costs through risk assessment and outcome measurement. An affected patient is entitled to nothing less, and stakeholders are responsible to utilize tools currently available. Implementation offers a significant challenge to the entire primary immunodeficiency community.

Quality of Primary Care for Children With Disabilities Enrolled in Medicaid.

OBJECTIVE: The quality of primary care delivered to Medicaid-insured children with disabilities (CWD) is unknown. We used the newly validated CWD algorithm (CWDA) to examine CWD prevalence among Medicaid enrollees 1 to 18 years old, primary care quality for CWD, and differences in primary care quality for CWD and non-CWD. METHODS: Cross-sectional study using 2008 Medicaid Analytic eXtract claims data from 9 states, including children with at least 11 months of enrollment (N = 2,671,922 enrollees). We utilized CWDA to identify CWD and applied 12 validated or endorsed pediatric quality measures to assess preventive/screening, acute, and chronic disease care quality. We compared quality for CWD and non-CWD unmatched and matched on age, sex, and number of nondisabling chronic conditions and outpatient encounters. RESULTS: CWDA identified 5.3% (n = 141,384) of our study population as CWD. Care quality levels for CWD were below 50% on 8 of 12 quality measures (eg, adolescent well visits [44.9%], alcohol/drug treatment engagement [24.9%]). CWD care quality was significantly better than the general population of non-CWD by +0.9% to +15.6% on 9 measures, but significantly worse for 2 measures, chlamydia screening (-3.4%) and no emergency department visits for asthma (-5.0%; all P < .01 to .001). Differences in care quality between CWD and non-CWD were generally smaller or changed direction when CWD were compared to a general population or matched group of non-CWD. CONCLUSIONS: One in 20 Medicaid-insured children is CWD, and the quality of primary care delivered to CWD is suboptimal. Areas needing improvement include preventive/screening, acute care, and chronic disease management.