Health education to promote knowledge about sickle cell disease and newborn screening in pregnant women: a community-based pilot study using the healthy beginning initiative.

BACKGROUND: Pregnancy presents a critical period for any maternal and child health intervention that may impact the health of the newborn. With low antenatal care attendance by pregnant women in health facilities in Nigeria, community-based programs could enable increased reach for health education about sickle cell disease (SCD) and newborn screening (NBS) among pregnant women. This pilot study aimed to assess the effect of education on the knowledge about SCD and NBS among pregnant women using the Healthy Beginning Initiative, a community-based framework. METHODS: A pre-post study design was used to evaluate knowledge of SCD and NBS in a convenience sample of 89 consenting pregnant women from three communities. Participants were given surveys prior to and following completion of a health education session. McNemar's test was used to compare the proportion of participants with correct responses. The level of significance was taken as p < 0.05. RESULTS: Compared to pre-test values, post-test values showed that participants understood that SCD is hereditary (93.3% vs. 69.7%), both parents must have at least one gene for someone to have SCD (98.9% vs. 77.5) and blood test is the right way to know if one has SCD (98.8% vs. 78.7%). Also, a large proportion of participants (post-test ~ 89.9%; compared to pre-test ~ 23.6%) understood that the chance of conceiving a child with SCD was 25% for a couple with the sickle cell trait (SCT). Knowledge of the possibility of diagnosing SCD shortly after birth was highly increased in the post test phase of the study when compared to the pre-test phase (93.3% vs. 43.9%, respectively). Concerning the overall knowledge scores, those with high level of knowledge significantly increase from 12.6% pretest to 87.4% posttest (p = 0.015). CONCLUSION: The health education intervention was associated with significant improvement on almost all measures of SCD knowledge. Focused health education for pregnant women using community structures can improve knowledge of SCD and NBS.

The Association between Direct Oral Anticoagulants Prescribing Behavior and Non-Valvular Atrial Fibrillation Outcomes: An Instrumental Variable Analysis of Real-World Data.

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death.

Urgent Follow-up after Outpatient Nonstress Tests and the Potential for Fetal Monitoring at Home.

OBJECTIVE: This study aimed to measure the proportion of patients needing urgent clinical follow-up after an abnormal outpatient nonstress test (NST). We further sought to capture the patient perspective on the acceptability of performing NSTs at home. STUDY DESIGN: A retrospective cohort study was performed over a 2-year period to determine the frequency of abnormal NSTs in a hospital-based, antepartum testing unit in patients greater than or equal to 32 weeks' gestation. The proportion of patients who delivered within 24 hours of an abnormal NST was also determined. A cross-sectional, web-based patient survey was conducted to obtain insight into the patient's comfort level with potentially performing NSTs at home. RESULTS: The chart review yielded 665 patients who underwent 2,122 NSTs at greater than or equal to 32 weeks. Of the 2,122 NSTs, 111 were categorized as abnormal and required urgent clinical follow-up, or 5.2% (95% confidence interval [CI] 4.3, 6.3%). Of the 665 patients, 13 delivered within 24 hours of an abnormal NST, or 2.0% (95% CI 1.0, 3.3%). In the web-based survey, the proportion of respondents who would feel comfortable or very comfortable conducting NSTs at home was 87/125, or 69.6% (95% CI 60.9, 77.1%). CONCLUSION: This study revealed that 5.2% of NSTs performed in a hospital-based antepartum testing unit were abnormal and required urgent clinical follow-up. Of the patients being followed in the antepartum testing unit, 2.0% delivered within 24 hours of an abnormal NST. The majority of the survey respondents indicated they would feel comfortable performing NSTs at home. The present study adds important information regarding the risks and benefits of NSTs at home. KEY POINTS: · Telehealth for NSTs offers advantages over in-person NSTs.. · The proportion of NSTs that need urgent follow-up was 5.2%.. · A majority of patients are interested in telehealth for NSTs.. · Guidelines are needed before adoption of telehealth for NSTs..

Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder.

Importance: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. Objective: To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test. Design, Setting, and Participants: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021. Exposure: Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform. Main Outcomes and Measures: Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care). Results: A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis. Conclusions and Relevance: The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.

Anti-fibrotic therapy and lung transplant outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis. OBJECTIVES: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications. METHODS: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone. RESULTS: Among patients taking nintedanib (n = 107) or pirfenidone (n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients [5.2%], p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients [5.7%], p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant. CONCLUSION: Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy < 5 medication half-lives before transplant. The frequency of other intra-operative and post-transplant complications did not appear to differ depending on when anti-fibrotic therapy was discontinued. REGISTRATION: clinicaltrials.gov NCT04316780: https://clinicaltrials.gov/ct2/show/NCT04316780.

Sex-specific inflammatory and white matter effects of prenatal opioid exposure: a pilot study.

BACKGROUND: Preclinical data demonstrate that opioids modulate brain reward signaling through an inflammatory cascade, but this relationship has yet to be studied in opioid-exposed neonates. METHODS: Saliva samples of 54 opioid-exposed and sex- and age-matched non-exposed neonates underwent transcriptomic analysis of inflammatory and reward genes. A subset of 22 neonates underwent brain magnetic resonance imaging (MRI) to evaluate white matter injury commonly associated with inflammatory response. Gene expression and brain MRI were compared between opioid- and non-exposed neonates and further stratified by sex and pharmacotherapy need. RESULTS: Opioid-exposed females regardless of pharmacotherapy need had higher expression of inflammatory genes than their male counterparts, with notable differences in the expression of CCL2 and CXCL1 in females requiring pharmacotherapy (p = 0.01 and 0.06, respectively). Opioid-exposed males requiring pharmacotherapy had higher expression of DRD2 than exposed females (p = 0.07), validating our prior research. Higher expression of IL1ß, IL6, TNFα, and IL10 was seen in opioid-exposed neonates with T1 white matter hyperintensity (WMH) compared to exposed neonates without WMH (p < 0.05). CONCLUSION: Prenatal opioid exposure may promote inflammation resulting in changes in reward signaling and white matter injury in the developing brain, with unique sex-specific effects. The actions of opioids through non-neuronal pathways need further investigation. IMPACT: Opioid-exposed neonates are at risk for punctate T1 white matter hyperintensity (WMH). Females carry a greater propensity for WMH. Salivary transcriptomic data showed significantly higher expression of inflammatory genes in opioid-exposed neonates with WMH than those without WMH, irrespective of pharmacotherapy need. Adding to prior studies, our findings suggest that prenatal opioid exposure may modulate white matter injury and reward signaling through a pro-inflammatory process that is sex specific. This novel study highlights the short-term molecular and structural effects of prenatal opioids and the need to elucidate the long-term impact of prenatal opioid exposure.

Use of a Continuous Glucose Monitoring System in High-Risk Hospitalized Noncritically Ill Patients With Diabetes After Cardiac Surgery and During Their Transition of Care From the Intensive Care Unit During COVID-19: A Pilot Study.

OBJECTIVE: Continuous glucose monitoring (CGM) has demonstrated benefits in managing inpatient diabetes. We initiated this single-arm pilot feasibility study during the COVID-19 pandemic in 11 patients with diabetes to determine the feasibility and accuracy of real-time CGM in patients who underwent cardiac surgery and whose care was being transitioned from the intensive care unit. METHODS: A Clarke error grid analysis was used to compare CGM and point-of-care measurements. The mean absolute relative difference (MARD) of the paired measurements was calculated to assess the accuracy of CGM for glucose measurements during the first 24 hours on CGM, the remaining time on CGM, and for different chronic kidney disease (CKD) strata. RESULTS: Overall MARD between point-of-care and CGM measurements was 14.80%. MARD for patients without CKD IV and V with an estimated glomerular filtration rate (eGFR) of ≥20 mL/min/1.73 m2 was 12.13%. Overall, 97% of the CGM values were within the no-risk zone of the Clarke error grid analysis. For the first 24 hours, a sensitivity analysis of the overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m2 was 15.42% ± 14.44% and 12.80% ± 7.85%, respectively. Beyond the first 24 hours, overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m2 was 14.54% ± 13.21% and 11.86% ± 7.64%, respectively. CONCLUSION: CGM has shown great promise in optimizing inpatient diabetes management in the noncritical care setting and after the transition of care from the intensive care unit with high clinical reliability and accuracy. More studies are needed to further assess CGM in patients with advanced CKD.

Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study.

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. METHODS: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. RESULTS: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. CONCLUSION: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFα-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h. Secondary endpoints included 28-day mortality, dynamic cytokine profiles, secondary infections, duration of supplemental oxygen support, and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 years, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953 ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days; 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Three deaths were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant Day 3 declines in IFN-, TNFα, IL-27, CRP, and ferritin occurred. IP-10 and CXCL-9 declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, P-value 0.0006). INTERPRETATION: Infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19.

Immune-related adverse events in cancer patients being treated with immune checkpoint inhibitors.

INTRODUCTION: With the increased use of immune checkpoint inhibitors (ICI), it is essential to improve our understanding of immune-related adverse events (irAE). To date, most studies describing irAE have been performed in clinical trial populations, which may not be an accurate description of irAE in real-world populations. Also, identification of patients at increased risk of irAE is needed as early recognition may improve irAE outcomes. METHODS: We performed a retrospective analysis of patients who received an ICI between January 2014 and October 2018 at a single institution (Tufts Medical Center). Each patient was followed for up to 12 months for the outcome of a physician-reported irAE. Kaplan-Meier curves were created for the time to development and resolution of initial irAE. A Cox proportional hazards model was created to evaluate whether the following variables were independent predictors of an initial irAE: age ≥65 years, female sex, non-Caucasian race, radiation in previous 6 months, current smoking status, melanoma, and combination ICI (ipilimumab and nivolumab). RESULTS: Of 131 patients followed, 57 patients (43.5%) developed at least one irAE at a median of 250 days (95% confidence interval (CI) 132 days-not estimable). The most common irAE included dermatitis, thyroid dysfunction, and pneumonitis. Nearly two-thirds of patients with an irAE had ICI therapy withdrawn, and nearly 60% had immunosuppression initiated. In multivariable analysis, we found a significant association between irAE development and age ≥65 years hazard ratio (HR) 1.80, 95% CI (1.03-3.14) and current smoking status (HR 2.26, 95% CI 1.06-4.82). DISCUSSION: We detected a high rate of irAE and that irAE and subsequent management can be clinically burdensome in this patient population. While further studies are needed to validate these findings, this study provides insights into the magnitude, time course, management of, and possible predictors of irAE in a real-world setting.

Differences in clinical and laboratory biomarkers for short and long-term respiratory outcomes in preterm neonates.

BACKGROUND: Pulmonary outcome of premature neonates has focused more on short-term than long-term respiratory morbidities. OBJECTIVE: Describe risk factors/biomarkers associated with short-term (bronchopulmonary dysplasia [BPD]) (supplemental oxygen use at 36 weeks postmenstrual age [PMA]) and longer-term (chronic respiratory morbidity [CRM]) (respiratory related symptoms, medications, medical/emergency visits, hospitalizations at 6-12 months corrected gestational age [CGA]) respiratory outcomes in a longitudinal cohort. DESIGN/METHODS: Neonates born at 24-29-week gestation were prospectively followed to 6-12-month CGA. Associations between clinical and laboratory risk factors/biomarkers of BPD and CRM were explored. RESULTS: Of 86 subjects, 94% survived. Outcomes were available for 89% at 36-week PMA (BPD present in 42% of infants) and 72% at 6-12-month CGA (CRM present in 47% of infants). For the 54 infants with known outcomes for both BPD and CRM, diagnoses were discordant in 41%. BPD was associated with lower birthweight and birthweight Z-score for GA, lower Apgar scores, more surfactant doses, higher SNAPPE-II scores, highest Day 1 inspired oxygen concentration, Day 7 oxygen use, prolonged ventilatory support, bacteremia, necrotizing enterocolitis, and treated patent ductus arteriosus. CRM was associated with lower Apgar scores, Day 7 oxygen use and higher urine vascular endothelial growth factor. Patterns of plasma and urine lipid oxidation products differed in the two outcomes. CONCLUSION: In this hypothesis generating and exploratory study, BPD and CRM were associated with different risk factors/biomarker patterns. Concordance between these two outcomes was weak. Strategies for reducing CRM should be studied in cohorts identified by appropriate early risk factors/biomarkers.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-α antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay, Eve Technologies), secondary infections, duration of supplemental oxygen support and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65yrs age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and further to 146 pg/ml at Day 14/discharge. Significant declines in IFN- γ , TNFα, IL-27, CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unmodified. IL-6 levels declined sharply among patients with baseline levels >10 pg/ml. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). INTERPRETATION: Consistent with a pathophysiological role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are required to formally assess mortality outcomes. Funding: National Center for Advancing Translational Sciences.

Nationwide utilization of cardiopulmonary bypass in cardiothoracic trauma: A retrospective analysis of the National Trauma Data Bank.

BACKGROUND: The American College of Surgeons Committee on Trauma requires that all level I trauma centers have cardiopulmonary bypass (CPB) capabilities immediately available. Despite this mandate, there are limited data on the utilization and clinical outcomes among trauma patients requiring CPB in the management of injuries. The aim of this study was to evaluate the current use of CPB in the care of trauma patients. METHODS: This is a retrospective analysis of the National Trauma Data Bank from 2010 to 2015. Adult patients sustaining cardiothoracic injuries who underwent surgical repair within the first 24 hours of admission were included. Propensity score matching was used to compare outcomes (in-hospital mortality, hospital length of stay (LOS), intensive care unit LOS, and complications) between patients who underwent CPB within the first 24 hours of admission and those with similar injuries who did not receive CPB. RESULTS: A total of 28,481 patients who met the inclusion criteria were identified, of whom 319 underwent CPB. Three-hundred three CPB patients were matched to 895 comparison patients who did not undergo CPB. Overall in-hospital mortality was 35%. Patients who were not treated with CPB had a significantly higher in-hospital mortality compared with those treated with CBP (odds ratio, 1.57; 95% confidence interval, 1.16-2.12; p = 0.003); however, complications were significantly lower in those who did not receive CPB (odds ratio, 0.63; 95% confidence interval, 0.47-0.86; p = 0.003). Hospital LOS (non-CPB: mean, 13.4 ± 16.3 days; CPB: mean, 14.7 ± 15.1 days; p = 0.23) and intensive care unit LOS (non-CPB: mean, 9.9 ± 10.7 days; CPB: mean, 10.1 ± 9.7 days; p = 0.08) did not differ significantly between groups. CONCLUSION: The use of CPB in the initial management of select cardiothoracic injuries is associated with a survival benefit. Further investigation is required to delineate which specific injuries would benefit the most from the use of CPB. LEVEL OF EVIDENCE: Therapeutic, level IV.

Effect of Ventral vs Dorsal Spinal Surgery on Patient-Reported Physical Functioning in Patients With Cervical Spondylotic Myelopathy: A Randomized Clinical Trial.

Importance: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon's discretion. Main Outcomes and Measures: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results: Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, -2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration: ClinicalTrials.gov Identifier: NCT02076113.

The Challenges of Using ICD codes to Perform a Comparative Analysis between Patients with Penetrating Cardiac Injuries who Underwent Non-Resuscitative Thoracotomy versus Sternotomy.

Background: Comparative morbidity after either sternotomy or non-resuscitative thoracotomy in penetrating cardiac injuries (PCI) is unknown. Methods: Retrospective review of adults with PCI who underwent either sternotomy or non-resuscitative thoracotomy using the National Trauma Data Bank 2007-2015. Since there is no unique International Classification of Diseases Procedure Coding System (ICD-PCS) codes assigned for resuscitative vs. non-resuscitative thoracotomy, and both procedures were coded as "thoracotomy", propensity score (PS) methods were applied to avoid inclusion of resuscitative thoracotomy. Results: Despite well PS matching on injury severity score the non-thoracotomy group compared to the sternotomy group had a significantly increased risk of mortality (30 percent vs 8 percent, p<0.0001). The morbidity differed as well-25 percent vs. 12 percent, p=0.0007. Conclusions: The differences in mortality in PCI patients who underwent non-resuscitative thoracotomy vs. sternotomy may be biased by unintentional inclusion of resuscitative thoracotomy. To accurately capture thoracotomy type, separate unique resuscitative and non-resuscitative thoracotomy procedure codes should be created in future revisions of the ICD PCS.

Acute Care Surgery Service Is Essential During a Nonsurgical Catastrophic Event, the COVID-19 Pandemic.

BACKGROUND: The role of an acute care surgery (ACS) service during the COVID-19 pandemic is not well established. METHODS: A retrospective review of the ACS service performance in an urban tertiary academic medical center. The study was performed between January and May 2020. The demographics, clinical characteristics, and outcomes of patients treated by the ACS service 2 months prior to the COVID surge (pre-COVID group) and during the first 2 months of the COVID-19 pandemic (surge group) were compared. RESULTS: Trauma and emergency general surgery volumes decreased during the surge by 38% and 57%, respectively; but there was a 64% increase in critically ill patients. The proportion of patients in the Department of Surgery treated by the ACS service increased from 40% pre-COVID to 67% during the surge. The ACS service performed 32% and 57% of all surgical cases in the Department of Surgery during the pre-COVID and surge periods, respectively. The ACS service managed 23% of all critically ill patients in the institution during the surge. Critically ill patients with and without confirmed COVID-19 infection treated by ACS and non-ACS intensive care units during the surge did not differ in demographics, indicators of clinical severity, or hospital mortality:13.4% vs. 13.5% (P = .99) for all critically ill patients; and 13.9% vs. 27.4% (P = .12) for COVID-19 critically ill patients. CONCLUSION: Acute care surgery is an "essential" service during the COVID-19 pandemic, capable of managing critically ill nonsurgical patients while maintaining the provision of trauma and emergent surgical services. LEVEL OF EVIDENCE: III. STUDY TYPE: Therapeutic.

Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome.

Importance: Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives: To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants: This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures: Prenatal opioid exposure. Main Outcomes and Measures: All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results: Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance: The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility.

Scientific Review Committees as part of institutional review of human participant research: Initial implementation at institutions with Clinical and Translational Science Awards.

INTRODUCTION: Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs). METHODS: SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations. RESULTS: Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures. CONCLUSIONS: The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.