Virtual Learning in Kindergarten Through Grade 12 During the COVID-19 Pandemic and Chronic Absenteeism.

Importance: Chronic absenteeism among kindergarten through grade 12 students has increased considerably after the COVID-19 pandemic. Objective: To examine the association between virtual learning during the 2020-2021 school year and chronic absenteeism during the 2021-2022 school year at the school district level. Design, Setting, and Participants: This cross-sectional study used a panel of 11 017 school districts throughout the US comprising kindergarten through grade 12 for the 2018-2019 and 2021-2022 school years. Exposures: The key covariates were the percentage of hybrid and virtual school days in the previous school year, with an assumption that these values in the 2018-2019 school year were zero. Main Outcome and Measures: Chronic absenteeism rates at the district level, which were regressed on the percentage of school days in a learning mode in the previous school year, demographic characteristic and socioeconomic status controls, plus district and year fixed effects. Observations were weighted by district enrollment, and SEs were clustered at the district level. Results: The dataset includes 11 017 school districts for 2 years and 22 034 observations. Chronic absenteeism rates increased by 13.5 percentage points, from a mean (SD) of 15.9% (8.1%) in the 2018-2019 school year to 29.4% (13.2%) in the 2021-2022 school year. Students whose schools had 100% virtual instruction during the COVID-19 pandemic had chronic absenteeism rates that were 6.9 percentage points (95% CI, 4.8-8.9 percentage points) higher than those that were 100% in person. Hybrid instruction was not associated with increased absenteeism. The association between virtual learning and chronic absenteeism varied by socioeconomic status, with the conditional correlation much larger for at-risk students; chronic absenteeism rates were 10.6 percentage points (95% CI, 7.2-14.1 percentage points) higher among students with 100% of days in virtual learning from districts in the top quintile of poverty rates compared with 100% in-persion districts. Conclusions and Relevance: In this cross-sectional study, chronic absenteeism rates were substantially higher in school districts that used virtual learning during the COVID-19 pandemic compared with in person. Understanding how to reduce chronic absenteeism and use virtual learning without potentially negative consequences are key policy questions moving forward.

CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension.

Background: Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. Objectives: This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model. Materials and Methods: Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters. Results: Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001). Conclusion: The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.

Hepatic Fibrosis Risk Factors in Extracardiac-Fontan Patients: Observations From a Single Center.

Objective: We reviewed our experience with transvenous liver biopsy-derived hepatic fibrosis scores and possible associated risk factors in those postextracardiac Fontan patients. Methods: We identified extracardiac-Fontan patients with postoperative durations <20 years who underwent cardiac catheterizations with transvenous hepatic biopsies between April 2012 and July 2022. If a patient underwent two liver biopsies, we averaged the two total fibrosis scores and concurrent time, pressure, and oxygen saturation data. We grouped patients by the following factors: (1) sex, (2) venovenous collaterals, and (3) type of functionally univentricular heart. We identified potential hepatic fibrosis risk factors as the following: female, presence of venovenous collaterals, and a functional univentricle of right-ventricular type. For statistical analysis, we used Kruskal-Wallis nonparametric testing. Results: We identified 127 patients who underwent 165 transvenous biopsies, with 38 patients undergoing 2 biopsies. We found that females with two additional risk factors had the highest median total fibrosis scores, 4 (1-8); males with <2 risk factors had the lowest median total fibrosis scores, 2 (0-5); and females with <2 additional risk factors and males with two risk factors were in the middle, median total fibrosis score 3 (0-6), P =.002; and there were no statistical differences for the other demographic or hemodynamic variables. Conclusions: For extracardiac-Fontan patients with similar demographic and hemodynamic variables, identifiable risk factors are associated with the degree of hepatic fibrosis.

Isolated Vascular Rings Are Common Cardiovascular Malformations.

OBJECTIVE: We investigated the prevalence of isolated vascular rings in the general population of Southern Nevada. METHODS: We identified those prenatally and postnatally diagnosed with an isolated vascular ring between January 2014 and December 2021. We included only those with vascular or ligamentous structures completely encircling the trachea and esophagus. To investigate the prevalence of isolated vascular rings, we included only those with situs solitus, levocardia, and no significant intracardiac malformations. RESULTS: We identified 112 patients. Of the 112, 66 (59%) were female. There were approximately 211,000 total live births in Southern Nevada for the study period, for an overall prevalence of 5.3 isolated vascular rings per 10 000 live births. However, for the years 2014 to 2017, the average prevalence figure was 3.5 per 10 000 live births, and for the years 2018 to 2021, the average prevalence figure was 7.1 (range 6.5-8.0) per 10 000 live births. Simultaneously, the prenatal detection rate rose from 66% to 86%. CONCLUSIONS: Isolated vascular rings are common cardiovascular malformations. As prenatal detection rates in the Southern Nevada general population approach 90%, the prevalence figures for isolated vascular rings appear to asymptote at about 7 per 10 000 live births.

The drug crisis and the living arrangements of children.

We examine the impact of the US drug crisis on children's living arrangements. Because factors that lead to drug use could also alter family structure, we instrument for the intensity of the drug crisis with cross-state exposure to marketing of the prescription opioid at the epicenter of the crisis. We find that the crisis increased the likelihood that a child lives away from a parent or in a household headed by a grandparent. Our results suggest that if drug use had remained at 1996 levels, 1.5 million fewer children aged 0-16 would have lived away from a parent in 2015.

Aortic Arch Laterality in Chromosome 22q11.2 Deletion Syndrome: Male-Female Difference.

We reviewed patients with chromosome 22q11.2 deletion syndrome. We analyzed cardiovascular findings in patients with confirmed chromosome 22q11.2 deletion syndrome live-born in Nevada between March 2007 and September 2020. We identified 60 patients. Of the 60 patients, 32 (53%) were female. Of the 60, 48 (80%) had a conotruncal abnormality (including isolated vascular rings): 23 of 32 (72%) for females versus 25 of 28 (89%) for males, P = .41. However, 11 (34%) of 32 females had a right aortic arch; whereas, 21 (75%) of 28 males had a right aortic arch, P = .007. In conclusion, in our patient cohort, we found conotruncal malformations were common. However, we noted males were statistically more likely to have a right aortic arch than females. To the best of our knowledge, this male-female aortic arch laterality difference in patients with chromosome 22q11.2 deletion syndrome has not been previously noted.

Isolated Balanced Complete Atrioventricular Septal Defects: Prenatal Detection and Outcome in Nevada.

We analyzed patients with isolated, balanced complete atrioventricular septal defects. We identified 71 patients born in Nevada, between January 2008 and December 2020. We also analyzed prenatal detection rates. Of the 71, 61 (85%) had trisomy 21, 1 (1%) had CHARGE syndrome and 22q.11 deletion, and 10 (14%) had no chromosomal abnormalities. Of the 71, 67 had prenatal care, and 43/67 (64%) were prenatally diagnosed. Prenatal detection rate for 2008-2012 was 9/20 (45%) and 18/21 (86%) for 2018-2020, P = .03. Of the 71, 67 underwent surgical repair with 1 current postpulmonary artery banding and 0 surgical deaths. Of the 67, 3 (4%) had heart block. Only 1 (1.5%) patient had reoperation for a mitral valve replacement. Of the 71, 67 (94%) are alive during a 6-year average (range = 0-12 years) follow-up. In conclusion, surgical and long-term outcomes were excellent. Also, high state-wide, general population prenatal detection rates were achieved.

A Bioinformatic Algorithm based on Pulmonary Endoarterial Biopsy for Targeted Pulmonary Arterial Hypertension Therapy.

Background: Optimal pharmacological therapy for pulmonary arterial hypertension (PAH) remains unclear, as pathophysiological heterogeneity may affect therapeutic outcomes. A ranking methodology based on pulmonary vascular genetic expression analysis could assist in medication selection and potentially lead to improved prognosis. Objective: To describe a bioinformatics approach for ranking currently approved pulmonary arterial antihypertensive agents based on gene expression data derived from percutaneous endoarterial biopsies in an animal model of pulmonary hypertension. Methods: We created a chronic PAH model in Micro Yucatan female swine by surgical anastomosis of the left pulmonary artery to the descending aorta. A baseline catheterization, angiography and pulmonary endoarterial biopsy were performed. We obtained pulmonary vascular biopsy samples by passing a biopsy catheter through a long 8 French sheath, introduced via the carotid artery, into 2- to 3-mm peripheral pulmonary arteries. Serial procedures were performed on days 7, 21, 60, and 180 after surgical anastomosis. RNA microarray studies were performed on the biopsy samples. Results: Utilizing the medical literature, we developed a list of PAH therapeutic agents, along with a tabulation of genes affected by these agents. The effect on gene expression from pharmacogenomic interactions was used to rank PAH medications at each time point. The ranking process allowed the identification of a theoretical optimum three-medication regimen. Conclusion: We describe a new potential paradigm in the therapy for PAH, which would include endoarterial biopsy, molecular analysis and tailored pharmacological therapy for patients with PAH.

Prenatal diagnosis of hypoplastic aortic arch without intracardiac malformations: The nevada experience.

OBJECTIVE: We reviewed our center's experience with neonatal and infant hypoplastic aortic arch, unassociated with intracardiac malformations, and investigated changes in prenatal detection rates over time for those requiring therapeutic procedures. METHODS: We identified all prenatal diagnoses of hypoplastic aortic arch with situs solitus, unassociated with intracardiac malformations, made in Nevada between May 2017 and April 2022. In addition, we identified all those 0-180 days old, with prenatal care, that underwent a surgical or interventional cardiac catheterization aortic arch procedure, whether prenatally or postnatally diagnosed. We excluded those with ventricular septal defects, functionally univentricular hearts, interrupted aortic arches, or any associated malformation requiring an additional surgical or interventional procedure ≤6 months old. Additionally, we calculated prenatal detection rates for those undergoing a surgical or interventional catheterization procedure for each of the 5 years. RESULTS: We identified 107 patients prenatally and postnatally. Of the 107 patients, 56 (34 prenatally diagnosed and 22 postnatally diagnosed) underwent an aortic arch procedure, and 51 additionally prenatally diagnosed, live-born infants did not undergo a procedure. Of the 56 procedures, 2 were by interventional catheterization, and 54 underwent a surgical repair. Prenatal detection for those undergoing a procedure statistically significantly increased over the 5 years from 38% to 82%, rho = 0.95 (p = .04). CONCLUSIONS: Currently in Nevada, our prenatal detection rate is >80% in the general population for those between 0 and 6 months old who require a therapeutic procedure for aortic arch obstruction without intracardiac malformations.

Hepatic fibrosis gender differences in extracardiac Fontan patients.

OBJECTIVE: We investigated possible gender differences for hepatic fibrosis in extracardiac-Fontan patients. METHODS: We identified extracardiac Fontan, performed between 2000 and 2016, who underwent cardiac catheterizations with transvenous hepatic biopsies between April 2012 and June 2022. We divided the patients by gender for analysis. RESULTS: We identified 116 patients who underwent 145 transvenous biopsies, with 29 patients undergoing 2 biopsies at an average interval of 5 ± 1 years. We divided the 145 biopsies into two groups: 1) 98/145 (68%) males and 2) 47/145 (32%) females. For the 47 female liver biopsy specimens, the median total fibrosis score was 3 (0-8), and for the 98 male liver biopsy specimens, the median total fibrosis score was 2 (0-6), p = .007. The average age at surgery for females was 3 ± 1 years and for males 3 ± 1 years, p = .99. Average Fontan duration at biopsy for females was 11 ± 5 years and for males, 10 ± 4 years, p = .23. No other demographic, anatomic, echocardiographic, laboratory, or hemodynamic findings demonstrated statistically significant gender differences. CONCLUSIONS: Females had statistically significantly higher median total fibrosis scores than males for the similar average age at extracardiac Fontan and average Fontan duration.

ORIGINS OF THE OPIOID CRISIS AND ITS ENDURING IMPACTS.

Overdose deaths involving opioids have increased dramatically since the 1990s, leading to the worst drug overdose epidemic in U.S. history, but there is limited empirical evidence about the initial causes. In this article, we examine the role of the 1996 introduction and marketing of OxyContin as a potential leading cause of the opioid crisis. We leverage cross-state variation in exposure to OxyContin's introduction due to a state policy that substantially limited the drug's early entry and marketing in select states. Recently unsealed court documents involving Purdue Pharma show that state-based triplicate prescription programs posed a major obstacle to sales of OxyContin and suggest that less marketing was targeted to states with these programs. We find that OxyContin distribution was more than 50% lower in "triplicate states" in the years after the drug's launch. Although triplicate states had higher rates of overdose deaths prior to 1996, this relationship flipped shortly after the launch and triplicate states saw substantially slower growth in overdose deaths, continuing even 20 years after OxyContin's introduction. Our results show that the introduction and marketing of OxyContin explain a substantial share of overdose deaths over the past two decades.

Complex neonatal congenital heart surgery in Nevada.

OBJECTIVE: We reviewed our center's surgical mortality rates for those who underwent a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category 4 or 5 neonatal cardiovascular surgery. METHODS: We identified all patients who underwent a STAT category 4 or 5 neonatal index cardiovascular surgical procedure between July 2015 and July 2021. RESULTS: We identified 239 patients. We divided them into two groups: (1) 42 (17.6%) ≤2.5 kg, and (2) 197 (82.4%) were >2.5 kg at the time of neonatal surgery. Of those ≤2.5 kg, 18/42 (42.9%) had syndromes or associated noncardiac malformations versus 34/197 (17.3%) of those >2.5 kg, p = .0093. Thirty-day discharge mortality for those ≤2.5 kg was 3/42 (7.1%) versus l0/197 (5.1%) for those >2.5 kg, p = .83. CONCLUSIONS: Weight at the time of surgery, presence of syndromes, and associated noncardiac malformations did not affect mortality in those undergoing complex neonatal STAT 4 or 5 category cardiovascular surgery.

Atresia of the Midportion of the Coronary Sinus: A Case Report.

A 12-year-old with a history of critical pulmonary stenosis and moderate right ventricular hypoplasia underwent neonatal pulmonary valve dilation, an aortopulmonary shunt, and an infant cavopulmonary anastomosis with aortopulmonary shunt takedown. During a diagnostic cardiac catheterization at 12 years of age, angiography showed interruption in the midportion of the coronary sinus, which required no intervention.

Decreasing Mortality for STAT 4 and 5 Neonatal Heart Surgeries Concurrent With Improving Prenatal Detection: The Nevada Experience.

Objective: Our objective was to investigate whether a relationship existed between our center's STAT 4 and 5 category surgical mortality and general-population prenatal detection rates in Nevada. Methods: We identified patients who underwent STAT 4 and 5 neonatal index cardiovascular surgeries at our center between October 2012 and September 2021. Additionally, we calculated prenatal detection rates for each of the 9 retrospective study years. We used descriptive statistics and nonparametric testing, including the Spearman Rho correlation (R) and the Mann-Whitney U-tests, with a significant P-value set at < .05. Results: We identified 356 patients. We noted a statistically significant increasing trend in prenatal detection percentages (rho = 0.79, P = .01), concurrent with a statistically significant decreasing trend in surgical mortality (rho = -0.82, P = .007). Conclusions: Despite encouraging results, we could not establish a cause-and-effect relationship between concurrent decreased surgical mortality and increased prenatal detection rates for patients undergoing STAT 4 and 5 surgical procedures at our center.

Nursing home quality, COVID-19 deaths, and excess mortality.

The COVID-19 pandemic in the US has been particularly devastating for nursing home residents. A key question is how have some nursing homes been able to effectively protect their residents, while others have not? Using data on the universe of US nursing homes, we examine whether establishment quality is predictive of COVID-19 mortality. Higher-quality nursing homes, as measured by CMS overall five-star rating, have substantially lower COVID-19 mortality through September of 2020. Quality does not predict the ability to prevent any COVID-19 resident or staff cases, but higher-quality establishments prevent the spread of resident infections conditional on having one. Preventing COVID-19 cases and deaths may come at some cost, as high-quality homes have substantially higher non-COVID deaths. The positive correlation between establishment quality and non-COVID mortality is strong enough that high-quality homes also have more total deaths than their low-quality counterparts and this relationship has grown with time. As of late April 2021, five-star homes have experienced 8.4 percent more total deaths than one-star homes.

Pulmonary Versus Systemic Outflow Obstruction in Functionally Univentricular Hearts with Isomerism: An Observation.

Our objective was to review our experience with isomerism associated with univentricular hearts and evaluate the prevalence of pulmonary versus systemic outflow obstruction. We identified those prenatally or postnatally diagnosed, between September 2004 and October 2021, with right and left isomerism and a functionally univentricular heart. We identified 62, 51 prenatally and 11 postnatally. Of the 62, 61 had prenatal care for an 84% (51/61) prenatal detection rate. Of the 62, 36 (58%) had right isomerism. Of the 51 prenatally diagnosed, 36 were live-born, 13 had fetal demise, and two underwent elective termination. Of the total 62, 43 had pulmonary outflow obstruction, 14 had systemic outflow obstruction, three had no outflow obstruction, and two had a common arterial trunk. However, between September 2004 and December 2019, 41 of 52 (79%) had pulmonary outflow obstruction, and between January 2000 and October 2021, 2 of 10 (20%) had pulmonary outflow obstruction (p = 001). We noted a statistically significant temporal change in the prevalence of pulmonary versus systemic outflow obstruction in those with isomeric situs and a functionally univentricular heart. Further, prenatal diagnosis exceeded 80% in the general population of Nevada.

Prenatal diagnosis of isolated perimembranous ventricular septal defects undergoing primary surgical repair in infancy.

OBJECTIVE: We retrospectively analyzed our center's experience with the prenatal diagnosis of isolated perimembranous ventricular septal defects that underwent primary surgical repair in infancy. METHODS: We identified patients born in Southern Nevada, between October 2012 and October 2020, with prenatal care that underwent surgical closure of an isolated large perimembranous ventricular septal defect between 1 and 12 months of age. The description at surgery defined ventricular septal defect morphology. We included only those with situs solitus, levocardia without dextroposition, and without any other cardiovascular abnormality. We analyzed prenatal detection rates for each of the eight years. RESULTS: We identified 81 patients. Of the 81, 35 (43%) had trisomy 21. We identified no other aneuploidies in those that underwent surgical repair; however, 1 had a 15q13.3 deletion syndrome, and 1 had a 22 q11.2 deletion syndrome. Of the 81, 27 (33%) overall were prenatally diagnosed. Increasing prenatal detection rates strongly correlated with time (R = 0.92, p = .002). CONCLUSIONS: Trisomy 21 is common in isolated perimembranous ventricular septal defects undergoing primary repair in infancy. Further, prenatal detection rates significantly improved over time, up to 65% detection in the current years.

Prenatal diagnosis of significant congenital heart disease and elective termination of pregnancy in Nevada.

OBJECTIVE: We investigated the relationship between prenatal detection of significant congenital heart disease and elective termination of pregnancy over time in Nevada. METHODS: We identified those prenatally or post-natally diagnosed with significant congenital cardiovascular malformations in Nevada with birth dates or estimated delivery dates between July 2012 and June 2021. RESULTS: We identified 1246. Of 1246, 69 underwent fetal demise, 42 had elective termination, and 1135 were live-born. Of the 1135 live-born, 1090 had prenatal care, of which 718 (66%) overall had a prenatal diagnosis of significant congenital heart disease. However, prenatal detection statistically significantly increased over time from 45 to 82%, p = .00001. Termination of pregnancy averaged 10% of those identified within the legal timeframe, and the rate did not statistically significantly increase with increasing prenatal detection rates, p = .56. Of the 42 undergoing elective termination, 23 (55%) had syndromes or comorbidities vs. 280 (25%) of the 1135 live-births, p = .0003. CONCLUSIONS: In Nevada, despite a statistically significant increase in prenatal detection of significant congenital heart disease over time, termination of pregnancy rates did not increase. Nevertheless, those undergoing elective termination were more likely to have associated syndromes or comorbidities.

Stage-1 Hybrid Palliation for High-Risk 2-Ventricle Patients with Ductal-Dependent Systemic Circulation in the Era of High Prenatal Detection.

OBJECTIVE: We reviewed our center's prenatal detection and surgical experience with high-risk, 2-ventricle patients, with complex congenital heart disease that underwent stage-1 hybrid palliation. METHODS: We retrospectively identified those born between March 2008 and March 2021 with 2-ventricle hearts, complex congenital cardiovascular malformations, and ductal-dependent systemic circulation that underwent stage-1 hybrid palliation consisting of surgical bilateral pulmonary artery banding and interventional catheterization placed ductus arteriosus stents. RESULTS: We identified 30 patients. Of the 30, 19 (63%) were male. For the 30, median gestational age was 35 weeks (29-39 weeks), and median birth weight was 2.2 kg (0.6-4.5 kg). Of the 30, 1 was transferred from an adjacent state, and 29 were born in Nevada. Of the 29 born in Nevada, overall statewide prenatal detection was 18 of 29 (62%); however, for 2008 to 2011 the prenatal detection rate was 3 of 10 (30%) and 15 of 19 (79%) for 2012 to 2021, P = .03. For the last 5 years, prenatal detection for Nevada-born patients was 8 of 8 (100%). Two full-term newborns, without a prenatal diagnosis, presented postnatally in extremis. For the 30 patients, there were 0 stage-1 hybrid palliation mortalities, 1 subsequent repair mortality, and 3 late nonsurgical deaths. CONCLUSIONS: Stage-1 hybrid palliation may result in excellent surgical outcomes for high-risk, 2-ventricle patients. Additionally, high rates of population-wide prenatal detection are possible for high-risk congenital heart disease, allowing prenatal planning and possibly reducing postnatal extremis presentations.