Estimates of congenital cytomegalovirus-attributable infant mortality in high-income countries: A review.

As many as 5%-10% of infants with symptomatic congenital cytomegalovirus (cCMV) disease, or 0.4%-0.8% of all liveborn infants with cCMV infection, die in early infancy in high-income countries. However, estimates are uncertain due to several potential biases that can result from data limitations and study designs. First, infants with cCMV infections who die prior to diagnosis, which usually occurs at 1-4 weeks after birth, may be excluded from both the count of deaths and the denominator of cCMV births, resulting in left truncation and immortal time biases. These 'biases' are features of the data and do not reflect bias on the part of researchers, but understanding the potential existence of threats to validity can help with interpretation of findings. Left truncation of infant deaths occurring prior to diagnosis of cCMV can result in understatement of the burden of infant deaths due to cCMV. Conversely, overestimation of infant deaths associated with symptomatic cCMV may occur in clinical case series owing to greater representation of relatively severely affected infants owing to ascertainment and referral biases. In this review, we summarise the characteristics of 26 studies that reported estimates of cCMV-associated infant deaths, including potential biases or limitations to which those estimates may have been subject. We discuss study designs whose implementation might generate improved estimates of infant deaths attributable to cCMV. More complete estimates of the overall public health impact of cCMV could inform current and future screening, prevention, and vaccine research.

Evidence and recommendation for mucopolysaccharidosis type II newborn screening in the United States.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.

Professional Fees for U.S. Hospital Care, 2016-2020.

BACKGROUND: The latest comprehensive diagnosis-specific estimates of hospital professional fees relative to facility fees are from 2004 to 2012. OBJECTIVE: Update professional fee ratio (PFR) estimates to improve cost analysis opportunities with hospital discharge data sources and compare them with previous PFR estimates. SUBJECTS: 2016-2020 MarketScan inpatient admissions and emergency department (ED) treat and release claims. MEASURES: PFR was calculated as total admission or ED visit payment divided by facility-only payment. This measure can be multiplied by hospital facility costs to yield a total cost estimate. RESEARCH DESIGN: Generalized linear regression models controlling for selected patient and service characteristics were used to calculate adjusted mean PFR per admission or ED visit by health payer type (commercial or Medicaid) and by selected diagnostic categories representing all clinical diagnoses (Major Diagnostic Category, Diagnostic Related Group, and Clinical Classification Software Revised). RESULTS: Mean 2016-2020 PFR was 1.224 for admissions with commercial payers (n = 6.7 million admissions) and 1.178 for Medicaid (n = 4.2 million), indicating professional payments on average increased total payments by 22.4% and 17.8%, respectively, above facility-only payments. This is a 9% and 3% decline in PFR, respectively, compared with 2004 estimates. PFR for ED visits during 2016-2020 was 1.283 for commercial payers (n = 22.2 million visits) and 1.415 for Medicaid (n = 17.7 million). This is a 12% and 5% decline in PFR, respectively, compared with 2004 estimates. CONCLUSIONS: Professional fees comprise a declining proportion of hospital-based care costs. Adjustments for professional fees are recommended when hospital facility-only financial data are used to estimate hospital care costs.

Inpatient Hospitalization Costs Associated with Birth Defects Among Persons Aged <65 Years - United States, 2019.

Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all.

Trends in Stimulant Prescription Fills Among Commercially Insured Children and Adults - United States, 2016-2021.

Prescription stimulant use, primarily for the treatment of attention-deficit/hyperactivity disorder (ADHD), has increased among adults in the United States during recent decades, while remaining stable or declining among children and adolescents (1,2). MarketScan commercial claims data were analyzed to describe trends in prescription stimulant fills before and during the COVID-19 pandemic (2016-2021) by calculating annual percentages of enrollees aged 5-64 years in employer-sponsored health plans who had one or more prescription stimulant fills overall and by sex and age group. Overall, the percentage of enrollees with one or more prescription stimulant fills increased from 3.6% in 2016 to 4.1% in 2021. The percentages of females aged 15-44 years and males aged 25-44 years with prescription stimulant fills increased by more than 10% during 2020-2021. Future evaluation could determine if policy and health system reimbursement changes enacted during the pandemic contributed to the increase in stimulant prescriptions. Stimulants can offer substantial benefits for persons with ADHD, but also pose potential harms, including adverse effects, medication interactions, diversion and misuse, and overdoses. Well-established clinical guidelines exist for ADHD care, but only for children and adolescents* (3); clinical practice guidelines for adult ADHD could help adults also receive accurate diagnoses and appropriate treatment.

Changes in Valganciclovir Use Among Infants with Congenital Cytomegalovirus Diagnosis in the United States, 2009-2015 and 2016-2019.

From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.

Direct costs of adhering to selected Duchenne muscular dystrophy Care Considerations: Estimates from a midwestern state.

INTRODUCTION/AIMS: The multidisciplinary Duchenne muscular dystrophy (DMD) Care Considerations were developed to standardize care and improve outcomes. We provide cumulative cost estimates for selected key preventive (ie, excluding new molecular therapies and acute care) elements of the care considerations in eight domains (neuromuscular, rehabilitation, respiratory, cardiac, orthopedic, gastrointestinal, endocrine, psychosocial management) independent of completeness of uptake or provision of nonpreventive care. METHODS: We used de-identified insurance claims data from a large midwestern commercial health insurer during 2018. We used Current Procedural Terminology and national drug codes to extract unit costs for clinical encounters representing key preventive elements of the DMD Care Considerations. We projected per-patient cumulative costs from ages 5 to 25 years for these elements by multiplying a schedule of recommended frequencies of preventive services by unit costs in 2018 US dollars. RESULTS: Assuming a diagnosis at age 5 years, independent ambulation until age 11, and survival until age 25, we estimated 670 billable clinical events. The 20-year per-patient cumulative cost was $174 701 with prednisone ($2.3 million with deflazacort) and an expected total of $12 643 ($29 194) for out-of-pocket expenses associated with those events and medications. DISCUSSION: Standardized monitoring of disease progression and treatments may reduce overall costs of illness. Costs associated with these services would be needed to quantify potential savings. Our approach demonstrates a method to estimate costs associated with implementation of preventive care schedules.

Health and economic outcomes of newborn screening for infantile-onset Pompe disease.

PURPOSE: To estimate health and economic outcomes associated with newborn screening (NBS) for infantile-onset Pompe disease in the United States. METHODS: A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared with clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course. RESULTS: Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared with clinical detection. The ICER was $379,000/QALY from a societal perspective and $408,000/QALY from the health-care perspective. Results were sensitive to the cost of enzyme replacement therapy. CONCLUSION: Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.

Labor market participation and productivity costs for female caregivers of minor male children with Duchenne and Becker muscular dystrophies.

INTRODUCTION/AIMS: Duchenne and Becker muscular dystrophies (DBMD) are X-linked neuromuscular disorders characterized by progressive muscle weakness, leading to decreased mobility and multisystem complications. We estimate productivity costs attributable to time spent by a parent caring for a male child under the age of 18 y with DBMD, with particular focus on female caregivers of boys with Duchenne muscular dystrophy (DMD) who have already lost ambulation. METHODS: Primary caregivers of males with DBMD in the Muscular Dystrophy Surveillance and Research Tracking Network (MD STARnet) were surveyed during 2011-2012 on family quality of life measures, including labor market outcomes. Of 211 respondents, 96 female caregivers of boys with DBMD were matched on state, year of survey, respondent's age, child's age, and number of minor children with controls constructed from Current Population Survey extracts. Regression analysis was used to estimate labor market outcomes and productivity costs. RESULTS: Caregivers of boys with DBMD worked 296 h less per year on average than caregivers of unaffected children, translating to a $8816 earnings loss in 2020 U.S. dollars. Caregivers of boys with DMD with ≥4 y of ambulation loss had a predicted loss in annualized earnings of $23,995, whereas caregivers of boys with DBMD of the same ages who remained ambulatory had no loss of earnings. DISCUSSION: Female caregivers of non-ambulatory boys with DMD face additional household budget constraints through income loss. Failure to include informal care costs in economic studies could understate the societal cost-effectiveness of strategies for managing DMD that might prolong ambulation.

Influenza vaccination rates and hospitalizations among Medicaid enrollees with and without sickle cell disease, 2009-2015.

BACKGROUND: Personswith sickle cell disease (SCD) face increased risks for pulmonary and infection-related complications. This study examines influenza vaccination coverage and estimates influenza-related morbidity among Medicaid enrollees with and without SCD. PROCEDURE: Influenza vaccination coverage and hospitalizations related to influenza and pneumonia/acute chest syndrome (ACS) during each influenza season from 2009-2010 to 2014-2015 were assessed among enrollees in the IBM MarketScan® Multi-State Medicaid Database. Enrollees with SCD were identified as enrollees with greater than or equal to three claims listing SCD within a 5-year period during 2003-2017. Vaccinations were identified in outpatient claims. Hospitalizations associated with influenza or pneumonia/ACS were identified using inpatient claims. This study includes a series of cross-sectional assessments by season. RESULTS: From 2009-2010 through 2014-2015 seasons, the SCD sample ranged from 5044 to 8651 enrollees; the non-SCD sample ranged from 1,841,756 to 3,796,337 enrollees. Influenza vaccination coverage was higher among enrollees with SCD compared with enrollees without SCD for all seasons (24.5%-33.6% and 18.2%-22.0%, respectively). Age-standardized rates of influenza-related hospitalizations were 20-42 times higher among SCD enrollees compared with non-SCD enrollees, and ACS/pneumonia hospitalizations were 18-29 times higher. Among enrollees with SCD, influenza-related hospitalization rates were highest among children aged 0-9 years. Among enrollees without SCD, influenza-related hospitalization rates were highest among adults aged 40-64 years. CONCLUSIONS: Although vaccine coverage was higher in persons with versus without SCD, efforts to increase influenza coverage further are warranted for this high-risk group, who experienced markedly higher rates of influenza and ACS/pneumonia hospitalizations during each season.

Treatment Discontinuation within 3 Years of Levothyroxine Initiation among Children Diagnosed with Congenital Hypothyroidism.

OBJECTIVES: To measure the rates of thyroid gland imaging and levothyroxine (L-T4) discontinuation and to assess whether discontinuation was monitored with thyroid-stimulating hormone testing in subjects with congenital hypothyroidism. STUDY DESIGN: This is a retrospective analysis of claims data from the IBM MarketScan Databases for children born between 2010 and 2016 and continuously enrolled in a noncapitated employer-sponsored private health insurance plan or in Medicaid for ≥36 months from the date of the first filled L-T4 prescription. RESULTS: There were 263 privately insured and 241 Medicaid-enrolled children who met the inclusion criteria. More privately insured than Medicaid-enrolled children had imaging between the first filled prescription and 180 days after the last filled prescription (24.3% vs 12.9%; P = .001). By 36 months, 35.7% discontinued L-T4, with no difference by insurance status (P = .48). Among those who discontinued, 29.1% of privately insured children and 47.7% of Medicaid-enrolled children had no claims for thyroid-stimulating hormone testing within the next 180 days (P = .01). CONCLUSIONS: Nearly one-third of children with suspected congenital hypothyroidism discontinued L-T4 by 3 years and fewer Medicaid-enrolled than privately insured children received timely follow-up thyroid-stimulating hormone testing. Future studies are indicated to understand the quality of care and developmental outcomes for children with congenital hypothyroidism and barriers to guideline adherence in evaluating for transient congenital hypothyroidism.

National Health Care Expenditures Associated With Disability.

BACKGROUND: In 2003, national disability-associated health care expenditures (DAHE) were $398 billion. Updated estimates will improve our understanding of current DAHE. OBJECTIVE: The objective of this study was to estimate national DAHE for the US adult population and analyze spending by insurance and service categories and to assess changes in spending over the past decade. RESEARCH DESIGN: Data from the 2013-2015 Medical Expenditure Panel Survey were used to estimate DAHE for noninstitutionalized adults. These estimates were reconciled with National Health Expenditure Accounts (NHEA) data and adjusted to 2017 medical prices. Expenditures for institutionalized adults were added from NHEA data. MEASURES: National DAHE in total, by insurance and service categories, and percentage of total expenditures associated with disability. RESULTS: DAHE in 2015 were $868 billion (at 2017 prices), representing 36% of total national health care spending (up from 27% in 2003). DAHE per person with disability increased from $13,395 in 2003 to $17,431 in 2015, whereas nondisability per-person spending remained constant (about $6700). Public insurers paid 69% of DAHE. Medicare paid the largest portion ($324.7 billion), and Medicaid DAHE were $277.2 billion. More than half (54%) of all Medicare expenditures and 72% of all Medicaid expenditures were associated with disability. CONCLUSIONS: The share of health care expenditures associated with disability has increased substantially over the past decade. The high proportion of DAHE paid by public insurers reinforces the importance of public programs designed to improve health care for people with disabilities and emphasizes the need for evaluating programs and health services available to this vulnerable population.

Infant Mortality Attributable to Birth Defects - United States, 2003-2017.

Birth defects are a leading cause of infant mortality in the United States, accounting for 20.6% of infant deaths in 2017 (1). Rates of infant mortality attributable to birth defects (IMBD) have generally declined since the 1970s (1-3). U.S. linked birth/infant death data from 2003-2017 were used to assess trends in IMBD. Overall, rates declined 10% during 2003-2017, but decreases varied by maternal and infant characteristics. During 2003-2017, IMBD rates decreased 4% for infants of Hispanic mothers, 11% for infants of non-Hispanic black (black) mothers, and 12% for infants of non-Hispanic white (white) mothers. In 2017, these rates were highest among infants of black mothers (13.3 per 10,000 live births) and were lowest among infants of white mothers (9.9). During 2003-2017, IMBD rates for infants who were born extremely preterm (20-27 completed gestational weeks), full term (39-40 weeks), and late term/postterm (41-44 weeks) declined 20%-29%; rates for moderate (32-33 weeks) and late preterm (34-36 weeks) infants increased 17%. Continued tracking of IMBD rates can help identify areas where efforts to reduce IMBD are needed, such as among infants born to black and Hispanic mothers and those born moderate and late preterm (32-36 weeks).

Infants with Congenital Disorders Identified Through Newborn Screening - United States, 2015-2017.

Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018,† approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences.

Administrative data identify sickle cell disease: A critical review of approaches in U.S. health services research.

To identify people living with sickle cell disease (SCD) and study their healthcare utilization, researchers can either use clinical records linked to administrative data or use billing diagnosis codes in stand-alone administrative databases. Correct identification of individuals clinically managed for SCD using diagnosis codes in claims databases is limited by the accuracy of billing codes in outpatient encounters. In this critical review, we assess the strengths and limitations of claims-based SCD case-finding algorithms in stand-alone administrative databases that contain both inpatient and outpatient records. Validation studies conducted using clinical records and newborn screening for confirmation of SCD case status have found that algorithms that require three or more nonpharmacy claims or one inpatient claim plus two or more outpatient claims with SCD codes show acceptable accuracy (positive predictive value and sensitivity) in children and adolescents. Future studies might seek to assess the accuracy of case-finding algorithms over the lifespan.

Preventing Breast, Cervical, and Colorectal Cancer Deaths: Assessing the Impact of Increased Screening.

INTRODUCTION: The US Preventive Services Task Force (USPSTF) recommends select preventive clinical services, including cancer screening. However, screening for cancers remains underutilized in the United States. The Centers for Disease Control and Prevention leads initiatives to increase breast, cervical, and colorectal cancer (CRC) screening. We assessed the number of avoidable deaths from increased screening, according to USPSTF recommendations, for CRC and female breast and cervical cancers. METHODS: We used model-based estimates of avoidable deaths for the lifetime of single-year age cohorts under the current and increased use of screening scenarios (data year 2016; analysis, 2018). We calculated prevented cancer deaths for each 1% increase in screening uptake and extrapolated to current level of screening (2016), current level plus 10 percentage points, and increasing screening to 90% and 100% of the eligible population. RESULTS: Increased use of screening from current levels to 100% would prevent an additional 2,821 deaths from breast cancer, 6,834 deaths from cervical cancer, and 35,530 deaths from CRC over a lifetime of the respective single-year cohort. Increasing use of CRC screening would prevent approximately 8.5 times as many deaths as the equivalent increase in use of breast cancer screening (women only), although twice as many people (men and women) would have to be screened for CRC. CONCLUSIONS: A large number of deaths could be avoided by increasing breast, cervical, and CRC screening. Public health programs incorporating strategies shown to be effective can help increase screening rates.

Population-based surveillance of haemophilia and patient outcomes in Indiana using multiple data sources.

INTRODUCTION: Epidemiological surveillance of haemophilia through linkage of medical records within a US state has not been conducted in 20 years. AIM: The Indiana Haemophilia Surveillance Project aims to identify all persons with haemophilia who resided in Indiana in 2011-2013 and to determine the percentage of patients in Indiana cared for at a federally recognized haemophilia treatment centre (HTC). METHODS: A retrospective review of medical charts was conducted to identify haemophilia cases during the surveillance years. Case-finding methods involved a variety of medical care resources including hospitals, administrative claims data and haematology/oncology clinic reports. RESULTS: In Indiana, 704 unique haemophilia cases were identified. Of those cases, 456 (64.8%) had factor VIII and 248 (35.2%) had factor IX deficiency. Among those with known severity levels (n = 685), 233 (34%) were severe, 185 (27%) were moderate, and 267 (39%) were mild. Overall, 81.7% of the haemophilia patients identified visited an HTC at least once during the three-year study period, which was the requirement for being considered an HTC patient. Age-adjusted prevalence for 2013 was 19.4 haemophilia cases per 100 000 males, 12.7 per 100 000 for factor VIII and 6.7 per 100 000 for factor IX. Incidence of haemophilia over the 10 years prior to the surveillance years was 1:3688 live male births in Indiana. During the surveillance years, 24 cases (3.4%) died. CONCLUSION: We observed higher incidence and prevalence of haemophilia in Indiana compared to previous national estimates, as well as higher HTC utilization among persons with haemophilia.

Actions in Support of Newborn Screening for Critical Congenital Heart Disease - United States, 2011-2018.

In 2011, the U.S. Department of Health and Human Services added critical congenital heart disease (CCHD), which occurs in two of every 1,000 births, to the list of conditions recommended to states for universal newborn screening (1). Without early detection, infants with CCHD are at risk for substantial morbidity and death in the first weeks and months of life (2). Based on 2007-2013 data, deaths from CCHD and other cardiac causes in infants aged <6 months significantly declined in infants born in eight states after they had fully implemented mandated newborn CCHD screening policies by June 2013 (3). CDC collaborated with the American Academy of Pediatrics (AAP) and the Association of Public Health Laboratories' Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) to update a 2015 report (4) on states' actions toward adopting and implementing policies supporting CCHD newborn screening. In 2018, all 50 states and the District of Columbia (DC) had implemented CCHD screening policies, and, with one exception, all states mandated that screening be done (California mandates that screening be offered). However, not all states had data systems in place for tracking all screening results and outcomes. Ongoing evaluation activities, which rely on screening data, could help identify program improvement opportunities and monitor the impact of early identification of CCHD.

US State-Level Infertility Insurance Mandates and Health Plan Expenditures on Infertility Treatments.

Objectives We aimed to examine the extent to which health plan expenditures for infertility services differed by whether women resided in states with mandates requiring coverage of such services and by whether coverage was provided through a self-insured plan subject to state mandates versus fully-insured health plans subject only to federal regulation. Methods This retrospective cohort study used individual-level, de-identified health insurance claims data. We included women 19-45 years of age who were continuously enrolled during 2011 and classified them into three mutually exclusive groups based on highest treatment intensity: in vitro fertilization (IVF), intrauterine insemination (IUI), or ovulation-inducing (OI) medications. Using generalized linear models, we estimated adjusted annual mean, aggregate, and per member per month (PMPM) expenditures among women in states with an infertility insurance mandate and those in states without a mandate, stratified by enrollment in a fully-insured or self-insured health plan. Results Of the 6,006,017 women continuously enrolled during 2011, 9199 (0.15%) had claims for IVF, 10,112 (0.17%) had claims for IUI, and 23,739 (0.40%) had claims for OI medications. Among women enrolled in fully insured plans, PMPM expenditures for infertility treatment were 3.1 times higher for those living in states with a mandate compared with states without a mandate. Among women enrolled in self-insured plans, PMPM infertility treatment expenditures were 1.2 times higher for mandate versus non-mandate states. Conclusions for Practice Recorded infertility treatment expenditures were higher in states with insurance reimbursement mandates versus those without mandates, with most of the difference in expenditures incurred by fully-insured plans.