Short report: Transition to International Classification of Diseases, 10th Revision and the prevalence of autism in a cohort of healthcare systems.

LAY ABSTRACT: Currently, the prevalence of autism spectrum disorder (henceforth "autism") is 1 in 36, an increasing trend from previous estimates. In 2015, the United States adopted a new version (International Classification of Diseases, 10th Revision) of the World Health Organization coding system, a standard for classifying medical conditions. Our goal was to examine how the transition to this new coding system impacted autism diagnoses in 10 healthcare systems. We obtained information from electronic medical records and insurance claims data from July 2014 through December 2016 for each healthcare system. We used member enrollment data for 30 consecutive months to observe changes 15 months before and after adoption of the new coding system. Overall, the rates of autism per 1000 enrolled members was increasing for 0- to 5-year-olds before transition to International Classification of Diseases, 10th Revision and did not substantively change after the new coding was in place. There was variation observed in autism diagnoses before and after transition to International Classification of Diseases, 10th Revision for other age groups. The change to the new coding system did not meaningfully affect autism rates at the participating healthcare systems. The increase observed among 0- to 5-year-olds is likely indicative of an ongoing trend related to increases in screening for autism rather than a shift associated with the new coding.

Considerations for Subgroup Analyses in Cluster-Randomized Trials Based on Aggregated Individual-Level Predictors.

In research assessing the effect of an intervention or exposure, a key secondary objective often involves assessing differential effects of this intervention or exposure in subgroups of interest; this is often referred to as assessing effect modification or heterogeneity of treatment effects (HTE). Observed HTE can have important implications for policy, including intervention strategies (e.g., will some patients benefit more from intervention than others?) and prioritizing resources (e.g., to reduce observed health disparities). Analysis of HTE is well understood in studies where the independent unit is an individual. In contrast, in studies where the independent unit is a cluster (e.g., a hospital or school) and a cluster-level outcome is used in the analysis, it is less well understood how to proceed if the HTE analysis of interest involves an individual-level characteristic (e.g., self-reported race) that must be aggregated at the cluster level. Through simulations, we show that only individual-level models have power to detect HTE by individual-level variables; if outcomes must be defined at the cluster level, then there is often low power to detect HTE by the corresponding aggregated variables. We illustrate the challenges inherent to this type of analysis in a study assessing the effect of an intervention on increasing COVID-19 booster vaccination rates at long-term care centers.

Pulmonary Artery Hypoplasia in Neonates With Tetralogy of Fallot.

BACKGROUND: Neonates with symptomatic tetralogy of Fallot (sTOF) with hypoplastic pulmonary arteries (hPA) are considered high risk. Data are needed to inform the impact of hPA on outcomes, and the ideal management strategy. OBJECTIVES: The objectives of this study were to quantify the impact of hPA on outcomes in neonates with sTOF and measure the impact of strategy on pulmonary artery (PA) growth in this population. METHODS: Neonates with sTOF from 2005 to 2017 were reviewed from the Congenital Cardiac Research Collaborative. Criteria for hPA included a unilateral PA z score <-2.0 and contralateral PA z score <0. Primary outcome was mortality. Secondary outcomes included reintervention and PA growth. RESULTS: We included 542 neonates with sTOF, including 188 (35%) with hPA and 354 (65%) with normal PA, with median follow-up of 4.1 years. Median right and left hPA z scores were -2.19 (25th-75th percentile: -2.55 to -1.94) and -2.23 (25th-75th percentile: -2.64 to -1.91), respectively. Staged repair (vs primary TOF repair) was less common in the hPA cohort (36 vs 44%; P = 0.07). Survival was similar between groups (unadjusted P = 0.16; adjusted P = 0.25). Reintervention was more common in the hPA group (HR: 1.28; 95% CI: 1.01-1.63; P = 0.044); there was no difference after definitive repair (HR: 1.21; 95% CI: 0.93-1.58; P = 0.16). PA growth at 1 year was greater in the hPA cohort, particularly for the right PA (P < 0.001). CONCLUSIONS: Despite perception, the presence of hPA in neonates with sTOF conferred no increase in overall hazard of mortality or reintervention after definitive repair. PA growth was superior in the hPA cohort. These findings suggest that the presence of hPA does not adversely impact outcomes in sTOF.

Microvascular cerebral blood flow response to intrathecal nicardipine is associated with delayed cerebral ischemia.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90 min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI.

Depression Treatment Initiation Among Patients With Versus Without Chronic Pain.

OBJECTIVE: The purpose of this study was to examine the extent to which the presence of chronic noncancer pain (CNCP) impacts the likelihood that patients with diagnoses of depression will initiate depression treatment compared with those without CNCP. METHODS: We performed a retrospective cohort study of Kaiser Permanente of Georgia members older than 18 years who received a diagnosis of depression. Demographics and medical history were extracted from the electronic health record database. Members were further classified by the presence or absence of a CNCP diagnosis. Outcomes of interest were treated as time dependent and included ( 1 ) time to fulfillment of a new antidepressant medication and ( 2 ) time to a follow-up mental health encounter. Outcomes were compared between members with and without a CNCP diagnosis using Kaplan-Meier survival curves and Cox proportional hazard regression models. RESULTS: During the study period, 22,996 members met the inclusion criteria and 27.4% had a diagnosis of CNCP. In the matched sample, there was no difference in the time to a new antidepressant fill among members with and without CNCP (hazard ratio = 0.96; 95% confidence interval = 0.90-1.02; p = .18). In contrast, members with CNCP were significantly less likely to have a new mental health encounter after diagnosis (hazard ratio = 0.87; 95% confidence interval = 0.81-0.94; p < .001). CONCLUSIONS: Patients with CNCP were significantly less likely to have a new mental health encounter after a depression diagnosis compared with patients without CNCP. Additional outreach and consideration may be needed to improve initiation of depression treatment for newly diagnosed patients with comorbid depression and CNCP.

Impact of COVID-19 on Trends in Outpatient Clinic Utilization: A Tale of 2 Departments.

BACKGROUND: The COVID-19 pandemic forced many US health care organizations to shift from mostly in-person care to a hybrid of virtual visits (VV) and in-person visits (IPV). While there was an expected and immediate shift to virtual care (VC) early in the pandemic, little is known about trends in VC use after restrictions eased. METHODS: This is a retrospective study using data from 3 health care systems. All completed visits from adult primary care (APC) and behavioral health (BH) were extracted from the electronic health record of adults aged 19 years and older from January 1, 2019 to June 30, 2021. Standardized weekly visit rates were calculated by department and site and analyzed using time series analysis. RESULTS: There was an immediate decrease in APC visits following the onset of the pandemic. IPV were quickly replaced by VV such that VV accounted for most APC visits early in the pandemic. By 2021, VV rates declined, and VC visits accounted for <50% of all APC visits. By Spring 2021, all 3 health care systems saw a resumption of APC visits as rates neared or returned to prepandemic levels. In contrast, BH visit rates remained constant or slightly increased. By April 2020, almost all BH visits were being delivered virtually at each of the 3 sites and continue to do so without changes to utilization. CONCLUSIONS: VC use peaked during the early pandemic period. While rates of VC are higher than prepandemic levels, IPV are the predominant visit type in APC. In contrast, VC use has sustained in BH, even after restrictions eased.

Patient Factors Associated With Use of Adult Primary Care and Virtual Visits During the COVID-19 Pandemic.

BACKGROUND: The delivery of adult primary care (APC) shifted from predominately in-person to modes of virtual care during the COVID-19 pandemic. It is unclear how these shifts impacted the likelihood of APC use during the pandemic, or how patient characteristics may be associated with the use of virtual care. METHODS: A retrospective cohort study using person-month level datasets from 3 geographically disparate integrated health care systems was conducted for the observation period of January 1, 2020, through June 30, 2021. We estimated a 2-stage model, first adjusting for patient-level sociodemographic, clinical, and cost-sharing factors, using generalized estimating equations with a logit distribution, along with a second-stage multinomial generalized estimating equations model that included an inverse propensity score treatment weight to adjust for the likelihood of APC use. Factors associated with APC use and virtual care use were separately assessed for the 3 sites. RESULTS: Included in the first-stage models were datasets with total person-months of 7,055,549, 11,014,430, and 4,176,934, respectively. Older age, female sex, greater comorbidity, and Black race and Hispanic ethnicity were associated with higher likelihood of any APC use in any month; measures of greater patient cost-sharing were associated with a lower likelihood. Conditional on APC use, older age, and adults identifying as Black, Asian, or Hispanic were less likely to use virtual care. CONCLUSIONS: As the transition in health care continues to evolve, our findings suggest that to ensure vulnerable patient groups receive high quality health care, outreach interventions to reduce barriers to virtual care use may be warranted.

Virtual Care and Urinary Tract Infection Management: Comparing Ancillary Service Orders and Patient Order Fulfillments Between Virtual and In-person Encounters During the COVID-19 Pandemic in the United States.

BACKGROUND: During the COVID-19 pandemic, more health care issues were being managed remotely. Urinary tract infections (UTIs) are being managed more often using telehealth although few reports compare the rate of UTI ancillary service orders placed and fulfilled during these visits. OBJECTIVES: We aimed to evaluate and compare the rate of ancillary service orders and order fulfillments in incident UTI diagnoses between virtual and in-person encounters. RESEARCH DESIGN: The retrospective cohort study involved 3 integrated health care systems: Kaiser Permanente (KP) Colorado, KP Georgia, and KP Mid-Atlantic States. SUBJECTS: We included incident UTI encounters from adult primary care data from January 2019 to June 2021. MEASURES: Data were categorized as: prepandemic (January 2019-March 2020), COVID-19 Era 1 (April 2020-June 2020), and COVID-19 Era 2 (July 2020-June 2021). UTI-specific ancillary services included medication, laboratory, and imaging. Orders and order fulfillments were dichotomized for analyses. Weighted percentages for orders and fulfillments were calculated using inverse probability treatment weighting from logistic regression and compared between virtual and in-person encounters using χ2 tests. RESULTS: We identified 123,907 incident encounters. Virtual encounters increased from 13.4% prepandemic to 39.1% in COVID-19 Era 2. Ancillary service orders from virtual encounters were not placed as often as in-person encounters. However, the weighted percentage for ancillary service order fulfillment across all services remained above 65.3% across sites and eras, with many fulfillment percentages above 90%. CONCLUSIONS: Our study reported a high rate of order fulfillment for both virtual and in-person encounters. Health care systems should encourage providers to place ancillary service orders for uncomplicated diagnoses, such as UTI, to provide enhanced access to patient-centered care.

Management of Neck or Back Pain in Ambulatory Care: Did Visit Mode or the COVID-19 Pandemic Affect Provider Practice or Patient Adherence?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances have changed provider-patient interactions in ambulatory care: (1) the replacement of virtual for in-person visits and (2) the COVID-19 pandemic. We studied the potential impact of each event on provider practice and patient adherence by comparing the frequency of the association of provider orders, and patient fulfillment of those orders, by visit mode and pandemic period, for incident neck or back pain (NBP) visits in ambulatory care. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente regions (Colorado, Georgia, and Mid-Atlantic States) from January 2017 to June 2021. Incident NBP visits were defined from ICD-10 coded as primary or first listed diagnoses on adult, family medicine, or urgent care visits separated by at least 180 days. Visit modes were classified as virtual or in-person. Periods were classified as prepandemic (before April 2020 or the beginning of the national emergency) or recovery (after June 2020). Percentages of provider orders for, and patient fulfillment of orders, were measured for 5 service classes and compared on: virtual versus in-person visits, and prepandemic versus recovery periods. Comparisons were balanced on patient case-mix using inverse probability of treatment weighting. RESULTS: Ancillary services in all 5 categories at each of the 3 Kaiser Permanente regions were substantially ordered less frequently on virtual compared with in-person visits in both the prepandemic and recovery periods (both P ≤ 0.001). Conditional on an order, patient fulfillment within 30 days was high (typically ≥70%) and not likely meaningfully different between visit modes or pandemic periods. CONCLUSIONS: Ancillary services for incident NBP visits were ordered less frequently during virtual than in-person visits in both prepandemic and recovery periods. Patient fulfillment of orders was high, and not significantly different by mode or period.

Did Access to Ambulatory Care Moderate the Associations Between Visit Mode and Ancillary Services Utilization Across the COVID-19 Pandemic Period?

BACKGROUND/OBJECTIVE: In recent years, 2 circumstances changed provider-patient interactions in primary care: the substitution of virtual (eg, video) for in-person visits and the COVID-19 pandemic. We studied whether access to care might affect patient fulfillment of ancillary services orders for ambulatory diagnosis and management of incident neck or back pain (NBP) and incident urinary tract infection (UTI) for virtual versus in-person visits. METHODS: Data were extracted from the electronic health records of 3 Kaiser Permanente Regions to identify incident NBP and UTI visits from January 2016 through June 2021. Visit modes were classified as virtual (Internet-mediated synchronous chats, telephone visits, or video visits) or in-person. Periods were classified as prepandemic [before the beginning of the national emergency (April 2020)] or recovery (after June 2020). Percentages of patient fulfillment of ancillary services orders were measured for 5 service classes each for NBP and UTI. Differences in percentages of fulfillments were compared between modes within periods and between periods within the mode to assess the possible impact of 3 moderators: distance from residence to primary care clinic, high deductible health plan (HDHP) enrollment, and prior use of a mail-order pharmacy program. RESULTS: For diagnostic radiology, laboratory, and pharmacy services, percentages of fulfilled orders were generally >70-80%. Given an incident NBP or UTI visit, longer distance to the clinic and higher cost-sharing due to HDHP enrollment did not significantly suppress patients' fulfillment of ancillary services orders. Prior use of mail-order prescriptions significantly promoted medication order fulfillments on virtual NBP visits compared with in-person NBP visits in the prepandemic period (5.9% vs. 2.0%, P=0.01) and in the recovery period (5.2% vs. 1.6%, P=0.02). CONCLUSIONS: Distance to the clinic or HDHP enrollment had minimal impact on the fulfillment of diagnostic or prescribed medication services associated with incident NBP or UTI visits delivered virtually or in-person; however, prior use of mail-order pharmacy option promoted fulfillment of prescribed medication orders associated with NBP visits.

Health-care-Related Practices in Virtual Behavioral Health Treatment for Major Depression Before and During the COVID-19 Pandemic.

BACKGROUND: The abrupt shift to virtual care at the onset of the COVID-19 pandemic had the potential to disrupt care practices in virtual behavioral health encounters. We examined changes over time in virtual behavioral health-care-related practices for patient encounters with diagnoses of major depression. METHODS: This retrospective cohort study utilized electronic health record data from 3 integrated health care systems. Inverse probability of treatment weighting was used to adjust for covariates across 3 time periods, prepandemic (January 2019-March 2020), peak-pandemic shift to virtual care (April 2020-June 2020), and recovery of health care operations (July 2020-June 2021). First virtual follow-up behavioral health department encounters after an incident diagnostic encounter were examined for differences across the time periods in rates of antidepressant medication orders and fulfillments, and completion of patient-reported symptoms screeners in service of measurement-based care. RESULTS: Antidepressant medication orders declined modestly but significantly in 2 of the 3 systems during the peak-pandemic period but rebounded during the recovery period. There were no significant changes in patient fulfillment of ordered antidepressant medications. Completion of symptom screeners increased significantly in all 3 systems during the peak-pandemic period and continued to increase significantly in the subsequent period. CONCLUSIONS: A rapid shift to virtual behavioral health care was possible without compromising health-care-related practices. The transition and subsequent adjustment period have instead been marked by improved adherence to measurement-based care practices in virtual visits, signaling a potential new capacity for virtual health care delivery.

Development of a Common Data Model for a Multisite and Multiyear Study of Virtual Visit Implementation: A Case Study.

BACKGROUND/OBJECTIVE: In multisite studies, a common data model (CDM) standardizes dataset organization, variable definitions, and variable code structures and can support distributed data processing. We describe the development of a CDM for a study of virtual visit implementation in 3 Kaiser Permanente (KP) regions. METHODS: We conducted several scoping reviews to inform our study's CDM design: (1) virtual visit mode, implementation timing, and scope (targeted clinical conditions and departments); and (2) extant sources of electronic health record data to specify study measures. Our study covered the period from 2017 through June 2021. Integrity of the CDM was assessed by a chart review of random samples of virtual and in-person visits, overall and by specific conditions of interest (neck or back pain, urinary tract infection, major depression). RESULTS: The scoping reviews identified a need to address differences in virtual visit programs across the 3 KP regionsto harmonize measurement specifications for our research analyses. The final CDM contained patient-level, provider-level, and system-level measures on 7,476,604 person-years for KP members aged 19 years and above. Utilization included 2,966,112 virtual visits (synchronous chats, telephone visits, video visits) and 10,004,195 in-person visits. Chart review indicated the CDM correctly identified visit mode on>96% (n=444) of visits, and presenting diagnosis on >91% (n=482) of visits. CONCLUSIONS: Upfront design and implementation of CDMs may be resource intensive. Once implemented, CDMs, like the one we developed for our study, provide downstream programming and analytic efficiencies by harmonizing, in a consistent framework, otherwise idiosyncratic temporal and study site differences in source data.

Comparison of treatment strategies for neonates with tetralogy of Fallot and pulmonary atresia.

OBJECTIVE: Neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) but no major aorta-pulmonary collaterals are dependent on the arterial duct for pulmonary blood flow and require early intervention, either by primary (PR) or staged repair (SR) with initial palliation (IP) followed by complete repair (CR). The optimal approach has not been established. METHODS: Neonates with TOF/PA who underwent PR or SR were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Outcomes were compared between PR and SR (IP + CR) strategies. Propensity scoring was used to adjust for baseline differences. The primary outcome was mortality. Secondary outcomes included complications, length of stay, cardiopulmonary bypass and anesthesia times, reintervention (RI), and pulmonary artery (PA) growth. RESULTS: Of 282 neonates, 106 underwent PR and 176 underwent SR (IP: 144 surgical, 32 transcatheter). Patients who underwent SR were more likely to have DiGeorge syndrome and greater rates of mechanical ventilation before the initial intervention. Mortality was not significantly different. Duration of mechanical ventilation, inotrope use, and complication rates were similar. Cumulative length of stay, cardiopulmonary bypass, and anesthesia times favored PR (P ≤ .001). Early RI was more common in patients who underwent SR (rate ratio, 1.42; P = .003) but was similar after CR (P = .837). Conduit size at the time of CR was larger with SR. Right PA growth was greater with PR. CONCLUSIONS: In neonates with TOF/PA, SR is more common in greater-risk patients. Accounting for this, SR and PR strategies have similar mortality. Perioperative morbidities, RI, and right PA growth generally favor PR, whereas SR allows for larger initial conduit implantation.

Impact of viral respiratory infections on pulmonary exacerbations in children with cystic fibrosis.

BACKGROUND: Viral respiratory infections trigger pulmonary exacerbations (PEs) in children with cystic fibrosis (CF), but their clinical impact is not well understood. METHODS: A retrospective review of pediatric patients with CF who underwent nasopharyngeal respiratory viral panel testing during hospitalization for a PE between 2011 and 2018 was conducted. Patients were dichotomized into viral-positive and viral-negative groups. The results of spirometry, respiratory cultures, duration of hospitalization, and risk for subsequent PEs were analyzed. RESULTS: Ninety-five patients had 210 hospitalizations for PE (viral-positive = 71/210, 34%) during the study period. Rhinovirus/enterovirus was the most common virus (52/71, 73%) identified. Viral-positive patients were younger (p < 0.001), had higher baseline forced expiratory volume in 1 s (FEV1) (p = 0.037), continued to maintain higher FEV1 at 3 and 6 months following PE (p = 0.003 and 0.002, respectively), and had a shorter duration of hospitalization (p = 0.006) compared to the viral-negative group. There was no difference between the two groups in the rate of recovery of FEV1 at 3 and 6 months following PE (p = 0.71 and 0.405, respectively), time to the next PE (hazard ratio = 1.34, p = 0.157), number of subsequent PEs in 6 months (p = 0.99), or Pseudomonas aeruginosa (PA) acquisition (p = 0.707). CONCLUSIONS: In this single pediatric CF center cohort, one-third of PEs requiring hospitalization were associated with a viral infection, with rhinovirus/enterovirus being the most common. Viral-positive PEs were not associated with a greater decline or delayed recovery of lung function, increased risk for PA acquisition, shortened duration to next PE, longer hospital stay, or an increase in the frequency of subsequent PEs in 6 months compared to viral-negative PEs.

Development and comparison of immunologic assays to detect primary RSV infections in infants.

Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children. The RSV immune state of the young child, i.e., previously RSV infected or not, is important to the conduct and interpretation of epidemiology studies and vaccine clinical trials. To address the need for sensitive assays to detect immunologic evidence of past infection, we developed, characterized, and evaluated 7 assays including 4 IgG antibody enzyme immunoassays (EIAs), two neutralizing antibody assays, and an IFN-γ EliSpot (EliSpot) assay. The four IgG EIAs used a subgroup A plus subgroup B RSV-infected Hep-2 cell lysate antigen (Lysate), an expressed RSV F protein antigen (F), an expressed subgroup A G protein antigen (Ga), or an expressed subgroup B G protein (Gb) antigen. The two neutralizing antibody assays used either a subgroup A or a subgroup B RSV strain. The EliSpot assay used a sucrose cushion purified combination of subgroup A and subgroup B infected cell lysate. All seven assays had acceptable repeatability, signal against control antigen, lower limit of detection, and, for the antibody assays, effect of red cell lysis, lipemia and anticoagulation of sample on results. In 44 sera collected from children >6 months after an RSV positive illness, the lysate, F, Ga and Gb IgG EIAs, and the subgroup A and B neutralizing antibody assays, and the EliSpot assays were positive in 100%, 100%, 86%, 95%, 43%, and 57%, respectively. The Lysate and F EIAs were most sensitive for detecting RSV antibody in young children with a documented RSV infection. Unexpectedly, the EliSpot assay was positive in 9/15 (60%) of PBMC specimens from infants not exposed to an RSV season, possibly from maternal microchimerism. The Lysate and F EIAs provide good options to reliably detect RSV antibodies in young children for epidemiologic studies and vaccine trials.

Cohort profile: pathways to care among people with disorders of sex development (DSD).

PURPOSE: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS). PARTICIPANTS: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation. FINDINGS TO DATE: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS. FUTURE PLANS: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.

Impact of Management Strategy on Feeding and Somatic Growth in Neonates with Symptomatic Tetralogy of Fallot: Results from the Congenital Cardiac Research Collaborative.

OBJECTIVE: To evaluate early growth following primary or staged repair of neonatal symptomatic tetralogy of Fallot (sTOF). STUDY DESIGN: We performed a retrospective, multicenter cohort study of consecutive infants with sTOF who underwent initial intervention at age ≤30 days, from 2005 to 2017. Management strategies were either primary repair or staged repair (ie, initial palliation followed by complete repair). The primary outcome was change in weight-for-age z-score (ΔWAZ) from the initial intervention to age 6 ± 2 months. Secondary outcomes included method and mode of feeding, feeding-related medications, and feeding-related readmissions. Propensity score adjustment was used to account for baseline differences between groups. A secondary analysis was performed comparing patients stratified by the presence of adequate growth (6-month ΔWAZ > -0.5) or inadequate growth (6-month ΔWAZ ≤ -0.5), independent of treatment strategy. RESULTS: The study cohort included 143 primary repair subjects and 240 staged repair subjects. Prematurity was more common in the staged repair group. After adjustment, median ΔWAZ did not differ between treatment groups over the first 6 months of life (primary: -0.43 [IQR, -1.17 to 0.50]; staged: -0.31 [IQR, -1.31 to 0.71]; P = .55). For the entire cohort, ΔWAZ was negative (-0.36; IQR, -1.21 to 0.63). There were no between-group differences in the secondary outcomes. Secondary analysis revealed that the subjects with adequate growth were more likely to be orally fed at initial hospital discharge (P = .04). CONCLUSIONS: In neonates with sTOF, growth trajectory over the first 6 months of life was substandard, irrespective of treatment strategy. Those patients with adequate growth were more likely to be discharged from the index procedure on oral feeds.

Transcatheter Recanalization of Atretic Pulmonary Veins in Infants and Children.

BACKGROUND: Pulmonary vein stenosis is a progressive disease associated with a high rate of mortality in children. If left untreated, myofibroblastic proliferation can lead to pulmonary vein atresia (PVA). In our experience, transcatheter recanalization has emerged as a favorable interventional option. We sought to determine the acute success rate of recanalization of atretic pulmonary veins and mid-term outcomes of individual veins after recanalization. METHODS: We reviewed all patients with PVA at our institution between 2008 and 2020 diagnosed by either catheterization or cardiac computed tomography. All veins with successful recanalization were reviewed and procedural success rate and patency rate were noted. Competing risk analysis was performed to demonstrate outcomes of individual atretic veins longitudinally. RESULTS: Between 2008 and 2020, our institution diagnosed and treated 131 patients with pulmonary vein stenosis. Of these, 61 patients developed atresia of at least one pulmonary vein. In total, there were 97 atretic pulmonary veins within this group. Successful recanalization was accomplished in 47/97 (48.5%) atretic veins. No atretic pulmonary veins were successfully recanalized before 2012. The majority of veins were recanalized between 2017 and 2020-39/56 (70%). The most common intervention after recanalization was drug-eluting stent placement. At 2-year follow-up 42.6% of recanalized veins (20.6% of all atretic veins) remained patent with a median of 4 reinterventions per person. CONCLUSIONS: Transcatheter recanalization of PVA can result in successful reestablishment of flow to affected pulmonary veins in many cases. Drug-eluting stent implantation was the most common intervention performed immediately post-recanalization. Vein patency was maintained in 42.6% of patients at 2-year follow-up from recanalization with appropriate surveillance and reintervention. Overall, only a small portion of atretic pulmonary veins underwent successful recanalization with maintained vessel patency at follow-up. Irrespective of successful recanalization, there was no detectable survival difference between the more recently treated PVA cohort and non-PVA cohort.

Palliation Strategy to Achieve Complete Repair in Symptomatic Neonates with Tetralogy of Fallot.

Neonates with symptomatic tetralogy of Fallot (sTOF) may undergo palliations with varying physiology, namely systemic to pulmonary artery connections (SPC) or right ventricular outflow tract interventions (RVOTI). A comparison of palliative strategies based on the physiology created is lacking. Consecutive sTOF neonates undergoing SPC or RVOTI from 2005-2017 were reviewed from the Congenital Cardiac Research Collaborative. The primary outcome was survival with successful complete repair (CR) by 18 months. A variety of secondary outcomes were assessed including overall survival, hospitalization-related comorbidities, and interstage reinterventions. Propensity score adjustment was utilized to compare treatment strategies. The cohort included 252 SPC (surgical shunt = 226, ductus arteriosus stent = 26) and 68 RVOTI (balloon pulmonary valvuloplasty = 48, RVOT stent = 11, RVOT patch = 9) patients. Genetic syndrome (29 [42.6%] v 75 [29.8%], p = 0.04), weight < 2.5 kg (28 [41.2%] v 68 [27.0%], p = 0.023), bilateral pulmonary artery Z-score < - 2 (19 [28.0%] v 36 [14.3%], p = 0.008), and pre-intervention antegrade flow (48 [70.6%] v 104 [41.3%], p < 0.001) were more common in RVOTI. Significant center differences were noted (p < 0.001). Adjusted survival to CR by 18 months (HR = 0.87, 95% CI = 0.63-1.21, p = 0.41) and overall survival (HR = 2.08, 95% CI = 0.93-4.65, p = 0.074) were similar. RVOTI had increased interstage reintervention (HR = 2.15, 95% CI = 1.36-3.99, p = 0.001). Total anesthesia (243 [213, 277] v 328 [308, 351] minutes, p < 0.001) and cardiopulmonary bypass times (117 [103, 132] v 151 [143, 160] minutes, p < 0.001) favored RVOTI. In this multicenter comparison of physiologic palliation strategies for sTOF, survival to successful CR and overall survival were similar; however, reintervention burden was significantly higher in RVOTI.