Systemic Absorption of Lidocaine from Continuous Erector Spinae Plane Catheters After Congenital Cardiac Surgery: A Retrospective Study.

OBJECTIVES: To examine postoperative serum lidocaine levels in patients with intermittent lidocaine bolus erector spinae plane block (ESPB) catheters after cardiac surgery with or without cardiopulmonary bypass (CPB). DESIGN: A retrospective study. SETTING: Single-center pediatric quaternary teaching hospital. PARTICIPANTS: Patients who received ESPB catheters after congenital cardiac surgery from April 2018 to March 2019. INTERVENTIONS: Postoperative serum lidocaine levels were extracted from the record. MEASUREMENTS AND MAIN RESULTS: Twenty-seven of 40 patients were included in the final analyses (19 with CPB and 8 with no CPB, age 1-47 years, undergoing congenital heart repair). Patients who received ropivacaine or were missing data were excluded. The initial intraoperative bolus of lidocaine ranged from 0- to- 3.72 mg/kg, and the range of postoperative intermittent lidocaine boluses ranged from 0.35- to- 0.83 mg/kg, which were administered every hour. Serum lidocaine levels were measured by the hospital laboratory and ranged from <0.05- to- 3.0 µg/mL in the CPB group and from <0.05- to- 3.2 µg/mL in the no- CPB group. CPB was not associated with differences in lidocaine levels when controlling for time (P = 0.529). Lidocaine concentrations ranged from 0.50- to- 1.68 µg/mL in the CPB group and 0.86- to- 2.07 µg/mL in the no- CPB group. There was a normally distributed overall mean peak level of 1.818 ± standard deviation of 0.624 µg/mL, with 95% confidence interval of 0.57- to- 3.06 µg/mL. No patients had clinical signs of toxicity. CONCLUSION: Postoperative serum lidocaine concentrations did not appreciably differ due to CPB. Serum lidocaine concentrations did not reach near- toxic doses despite the presence of additional lidocaine in the cardioplegia. The results suggested that lidocaine for ESPBs after cardiac surgery is below systemic toxic range at the doses described.

A retrospective cohort study of predictors and interventions that influence cooperation with mask induction in children.

BACKGROUND: Uncooperative pediatric mask induction is linked to perioperative anxiety. Although some risk factors for uncooperative inductions have been reported, there are no large cohort studies that identify intrinsic patient characteristics associated with cooperation. AIM: The primary aim was to identify patient characteristics associated with cooperative mask inductions. The secondary aim was to determine whether preoperative interventions were associated with increased cooperation. METHODS: This retrospective cohort study included patients 2-11 years old and ASA class I-IV who underwent mask induction. Our primary outcome of interest was cooperation with mask induction, which was correlated against the Induction Compliance Checklist. The variables analyzed for association with cooperation were age, sex, ASA class, class of surgery, preferred language, and race. Interventions examined for association with induction cooperation included premedication with midazolam, exposure to distraction technology, parental presence, and the presence of a Child Life Specialist. Multivariate mixed-effects logistic regression was used to assess the relationship between patient characteristics and cooperation. A separate multivariate mixed-effects logistic regression was used to examine the association between preoperative interventions and cooperation. RESULTS: 9692 patients underwent 23 474 procedures during the study period. 3372 patients undergoing 5980 procedures met inclusion criteria. The only patient characteristic associated with increased cooperation was age (OR 1.20, p-value 0.03). Involvement of Child Life Specialists was associated with increased cooperation (OR 4.44, p-value = 0.048) while parental/guardian presence was associated with decreased cooperation (OR 0.38, p-value = 0.002). CONCLUSION: In this cohort, increasing age was the only patient characteristic found to be associated with increased cooperation with mask induction. Preoperative intervention by a Child Life Specialists was the sole intervention associated with improved cooperation.

Trends in Direct Hospital Payments to Anesthesia Groups: A Retrospective Cohort Study of Nonacademic Hospitals in California.

BACKGROUND: In addition to payments for services, anesthesia groups in the United States often receive revenue from direct hospital payments. Understanding the magnitude of these payments and their association with the hospitals' payer mixes has important policy implications. METHODS: Using a dataset of financial reports from 240 nonacademic California hospitals between 2002 and 2014, the authors characterized the prevalence and magnitude of direct hospital payments to anesthesia groups, and analyzed the association between these payments and the fraction of anesthesia revenue derived from public payers (e.g., Medicaid). RESULTS: Of hospitals analyzed, 69% (124 of 180) made direct payments to an anesthesia group in 2014, compared to 52% (76 of 147) in 2002; the median payment increased from $242,351 (mean, $578,322; interquartile range, $72,753 to $523,861; all dollar values in 2018 U.S. dollars) to $765,128 (mean, $1,295,369; interquartile range, $267,006 to $1,503,163) during this time period. After adjusting for relevant covariates, hospitals where public insurers accounted for a larger fraction of anesthesia revenues were more likely to make direct payments to anesthesia groups (ß = 0.45; 95% CI, 0.10 to 0.81; P = 0.013), so that a 10-percentage point increase in the fraction of anesthesia revenue derived from public payers would be associated with a 4.5-percentage point increase in the probability of receiving any payment. Among hospitals making payments, our results (ß = 2.10; 95% CI, 0.74 to 3.45; P = 0.003) suggest that a 1-percentage point increase in the fraction of anesthesia revenue derived from public payers would be associated with a 2% relative increase in the amount paid. CONCLUSIONS: Direct payments from hospitals are becoming a larger financial consideration for anesthesia groups in California serving nonacademic hospitals, and are larger for groups working at hospitals serving publicly insured patients.

Preoperative depression, lumbar fusion, and opioid use: an assessment of postoperative prescription, quality, and economic outcomes.

OBJECTIVE Preoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs. METHODS A retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug-use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs. RESULTS The authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (ß = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17-1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95-0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03-1.25), revision fusions (OR 1.15, 95% CI 1.05-1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04-1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84-1.01). Preoperative depression also resulted in increased costs at 1 (ß = 0.06, p < 0.001) and 2 (ß = 0.09, p < 0.001) years postoperatively. CONCLUSIONS Although these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Stop Signal Reaction Time Deficits in a Lifetime Obsessive-Compulsive Disorder Sample.

OBJECTIVES: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. METHODS: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. RESULTS: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. CONCLUSIONS: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785-789).

Ion channels and schizophrenia: a gene set-based analytic approach to GWAS data for biological hypothesis testing.

Schizophrenia is a complex genetic disorder. Gene set-based analytic (GSA) methods have been widely applied for exploratory analyses of large, high-throughput datasets, but less commonly employed for biological hypothesis testing. Our primary hypothesis is that variation in ion channel genes contribute to the genetic susceptibility to schizophrenia. We applied Exploratory Visual Analysis (EVA), one GSA application, to analyze European-American (EA) and African-American (AA) schizophrenia genome-wide association study datasets for statistical enrichment of ion channel gene sets, comparing GSA results derived under three SNP-to-gene mapping strategies: (1) GENIC; (2) 500-Kb; (3) 2.5-Mb and three complimentary SNP-to-gene statistical reduction methods: (1) minimum p value (pMIN); (2) a novel method, proportion of SNPs per Gene with p values below a pre-defined α-threshold (PROP); and (3) the truncated product method (TPM). In the EA analyses, ion channel gene set(s) were enriched under all mapping and statistical approaches. In the AA analysis, ion channel gene set(s) were significantly enriched under pMIN for all mapping strategies and under PROP for broader mapping strategies. Less extensive enrichment in the AA sample may reflect true ethnic differences in susceptibility, sampling or case ascertainment differences, or higher dimensionality relative to sample size of the AA data. More consistent findings under broader mapping strategies may reflect enhanced power due to increased SNP inclusion, enhanced capture of effects over extended haplotypes or significant contributions from regulatory regions. While extensive pMIN findings may reflect gene size bias, the extent and significance of PROP and TPM findings suggest that common variation at ion channel genes may capture some of the heritability of schizophrenia.

Retrospective Review of the Safety and Efficacy of Virtual Reality in a Pediatric Hospital.

INTRODUCTION: Virtual reality (VR) is an emerging tool for anxiety and fear reduction in pediatric patients. VR use is facilitated by Certified Child Life Specialists (CCLS) at pediatric hospitals. The primary aim of this study was to retrospectively review the safety of VR by analyzing adverse events after the utilization of VR under CCLS supervision. Secondary objectives were to characterize the efficacy of VR in enhancing patient cooperation, describe the integration of VR into Child Life services, and identify interventions that accompanied VR. METHODS: The Stanford Chariot Program developed VR applications, customized VR interfaces, and patient head straps, and distributed these to CCLS. Chart review analyzed VR utilization through CCLS patient notes. Inclusion criteria were all patients ages 6 to 18-years-old who received a Child Life intervention. RESULTS: From June 2017 to July 2018, 31 CCLS saw 8,098 patients, 3,696 of which met age criteria with pre- and post-intervention cooperation data. Two hundred thirteen patients received VR with an accompanying intervention, while 34 patients received only VR. Adverse events were rare, and included increased anxiety (3.8%, n=8), dizziness (0.5%, n=1), and nausea (0.5%, n=1). Patients were more likely to be cooperative after receiving VR (99.5%, n=212) compared to pre-intervention (96.7%, n=206, p=0.041). VR use was most common in the perioperative setting (60%, n=128), followed by outpatient clinics (15%, n=32). CONCLUSION: VR is safe in pediatric patients with appropriate hardware, software, and patient selection. Side effects were rare and self-limited. VR appears to be associated with improvements in cooperation.

CheXaid: deep learning assistance for physician diagnosis of tuberculosis using chest x-rays in patients with HIV.

Tuberculosis (TB) is the leading cause of preventable death in HIV-positive patients, and yet often remains undiagnosed and untreated. Chest x-ray is often used to assist in diagnosis, yet this presents additional challenges due to atypical radiographic presentation and radiologist shortages in regions where co-infection is most common. We developed a deep learning algorithm to diagnose TB using clinical information and chest x-ray images from 677 HIV-positive patients with suspected TB from two hospitals in South Africa. We then sought to determine whether the algorithm could assist clinicians in the diagnosis of TB in HIV-positive patients as a web-based diagnostic assistant. Use of the algorithm resulted in a modest but statistically significant improvement in clinician accuracy (p = 0.002), increasing the mean clinician accuracy from 0.60 (95% CI 0.57, 0.63) without assistance to 0.65 (95% CI 0.60, 0.70) with assistance. However, the accuracy of assisted clinicians was significantly lower (p < 0.001) than that of the stand-alone algorithm, which had an accuracy of 0.79 (95% CI 0.77, 0.82) on the same unseen test cases. These results suggest that deep learning assistance may improve clinician accuracy in TB diagnosis using chest x-rays, which would be valuable in settings with a high burden of HIV/TB co-infection. Moreover, the high accuracy of the stand-alone algorithm suggests a potential value particularly in settings with a scarcity of radiological expertise.

Postoperative Opioid Use, Complications, and Costs in Surgical Management of Lumbar Spondylolisthesis.

STUDY DESIGN: Retrospective analysis on a national longitudinal database (2007-2014). OBJECTIVE: To determine the association between arthrodesis and complication rates, costs, surgical revision, and postoperative opioid prescription. SUMMARY OF BACKGROUND DATA: Arthrodesis in patients receiving laminectomy for lumbar spondylolisthesis remains controversial. However, population-level evidence to support the use of arthrodesis remains limited. METHODS: We identified 73,176 patient records and used coarsened exact matching to create comparable populations of patients who received laminectomy or laminectomy with arthrodesis. We use linear and logistic regression models to analyze the relationship between arthrodesis and postoperative complications, length of stay, costs, readmissions, surgical revisions, and postoperative opioid prescribing. RESULTS: Patients who underwent arthrodesis spent 1 more day in the hospital on average (P < 0.01), and had higher costs of care at their index visit ($24,126, P < 0.01), which were partially offset by lower costs of care over the 2 years following their procedure ($14,667 less in arthrodesis patients, P = 0.01). Patients with arthrodesis were less likely to have a surgical revision (odds ratio = 0.66, P < 0.01). Patients with arthrodesis used more opioids in the first 2 months following their procedure, but had comparable opioid use to patients undergoing laminectomy without arthrodesis in all other postoperative months over the next 2 years, and were not more or less likely to convert to chronic opioid use. Postoperative opioid prescription varied dramatically across states (P < 0.01); geographic variation in opioid use is substantially greater than differences in opioid use based on procedure performed. CONCLUSION: Arthrodesis is associated with reduced likelihood of surgical revision and increased use of opioids in the first 2 months following surgery, but not associated with greater or lesser opioid use beyond the initial 2 postoperative months. Geographic variation in opioid use is substantial even after accounting for patient characteristics and for whether patients underwent arthrodesis. LEVEL OF EVIDENCE: 3.

Geographic variation in the surgical management of lumbar spondylolisthesis: characterizing practice patterns and outcomes.

BACKGROUND CONTEXT: The role of arthrodesis in the surgical management of lumbar spondylolisthesis remains controversial. We hypothesized that practice patterns and outcomes for this patient population may vary widely. PURPOSE: This study aimed to characterize geographic variation in surgical practices and outcomes for patients with lumbar spondylolisthesis. STUDY DESIGN/SETTING: A retrospective analysis on a national longitudinal database between 2007 and 2014 was carried out. METHODS: We calculated arthrodesis rates, inpatient and long-term costs, and key quality indicators (eg, reoperation rates). Using linear and logistic regression models, we then calculated expected quality indicator values, adjusting for patient-level demographic factors, and compared these values with the observed values, to assess quality variation apart from differences in patient populations. RESULTS: We identified a cohort of 67,077 patients (60.7% female, mean age of 59.8 years (standard deviation, 12.0) with lumbar spondylolisthesis who received either laminectomy or laminectomy with arthrodesis. The majority of patients received arthrodesis (91.8%). Actual rates of arthrodesis varied from 97.5% in South Dakota to 81.5% in Oregon. Geography remained a significant predictor of arthrodesis even after adjusting for demographic factors (p<.001). Marked geographic variation was also observed in initial costs ($32,485 in Alabama to $78,433 in Colorado), 2-year postoperative costs ($15,612 in Arkansas to $34,096 in New Jersey), length of hospital stay (2.6 days in Arkansas to 4.5 in Washington, D.C.), 30-day complication rates (9.5% in South Dakota to 22.4% in Maryland), 30-day readmission rates (2.5% in South Dakota to 13.6% in Connecticut), and reoperation rates (1.8% in Maine to 12.7% in Alabama). CONCLUSIONS: There is marked geographic variation in the rates of arthrodesis in treatment of spondylolisthesis within the United States. This variation remains pronounced after accounting for patient-level demographic differences. Costs of surgery and quality outcomes also vary widely. Further study is necessary to understand the drivers of this variation.

Antidepressant Outcomes Predicted by Genetic Variation in Corticotropin-Releasing Hormone Binding Protein.

OBJECTIVE: Genetic variation within the hypothalamic-pituitary-adrenal (HPA) axis has been linked to risk for depression and antidepressant response. However, these associations have yet to produce clinical gains that inform treatment decisions. The authors investigated whether variation within HPA axis genes predicts antidepressant outcomes within two large clinical trials. METHOD: The test sample comprised 636 patients from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) who completed baseline and 8-week follow-up visits and for whom complete genotyping data were available. The authors tested the relationship between genotype at 16 candidate HPA axis single-nucleotide polymorphisms (SNPs) and treatment outcomes for three commonly used antidepressants (escitalopram, sertraline, and extended-release venlafaxine), using multivariable linear and logistic regression with Bonferroni correction. Response and remission were defined using the Hamilton Depression Rating Scale. Findings were then validated using the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study of outcome predictors in treatment-naive patients with major depression. RESULTS: The authors found that the rs28365143 variant within the corticotropin-releasing hormone binding protein (CRHBP) gene predicted antidepressant outcomes for remission, response, and symptom change. Patients homozygous for the G allele of rs28365143 had greater remission rates, response rates, and symptom reductions. These effects were specific to drug class. Patients homozygous for the G allele responded significantly better to the selective serotonin reuptake inhibitors escitalopram and sertraline than did A allele carriers. In contrast, rs28365143 genotype was not associated with treatment outcomes for the serotonin norepinephrine reuptake inhibitor venlafaxine. When patients were stratified by race, the overall effect of genotype on treatment response remained. In the validation sample, the GG genotype was again associated with favorable antidepressant outcomes, with comparable effect sizes. CONCLUSIONS: These findings suggest that a specific CRHBP SNP, rs28365143, may have a role in predicting which patients will improve with antidepressants and which type of antidepressant may be most effective. The results add to the foundational knowledge needed to advance a precision approach to personalized antidepressant choices.

DE NOVO MUTATIONS IN AUTISM IMPLICATE THE SYNAPTIC ELIMINATION NETWORK.

Autism has been shown to have a major genetic risk component; the architecture of documented autism in families has been over and again shown to be passed down for generations. While inherited risk plays an important role in the autistic nature of children, de novo (germline) mutations have also been implicated in autism risk. Here we find that autism de novo variants verified and published in the literature are Bonferroni-significantly enriched in a gene set implicated in synaptic elimination. Additionally, several of the genes in this synaptic elimination set that were enriched in protein-protein interactions (CACNA1C, SHANK2, SYNGAP1, NLGN3, NRXN1, and PTEN) have been previously confirmed as genes that confer risk for the disorder. The results demonstrate that autism-associated de novos are linked to proper synaptic pruning and density, hinting at the etiology of autism and suggesting pathophysiology for downstream correction and treatment.