Predicting risk of suicidal behavior from insurance claims data vs. linked data from insurance claims and electronic health records.

PURPOSE: Observational studies assessing effects of medical products on suicidal behavior often rely on health record data to account for pre-existing risk. We assess whether high-dimensional models predicting suicide risk using data derived from insurance claims and electronic health records (EHRs) are superior to models using data from insurance claims alone. METHODS: Data were from seven large health systems identified outpatient mental health visits by patients aged 11 or older between 1/1/2009 and 9/30/2017. Data for the 5 years prior to each visit identified potential predictors of suicidal behavior typically available from insurance claims (e.g., mental health diagnoses, procedure codes, medication dispensings) and additional potential predictors available from EHRs (self-reported race and ethnicity, responses to Patient Health Questionnaire or PHQ-9 depression questionnaires). Nonfatal self-harm events following each visit were identified from insurance claims data and fatal self-harm events were identified by linkage to state mortality records. Random forest models predicting nonfatal or fatal self-harm over 90 days following each visit were developed in a 70% random sample of visits and validated in a held-out sample of 30%. Performance of models using linked claims and EHR data was compared to models using claims data only. RESULTS: Among 15 845 047 encounters by 1 574 612 patients, 99 098 (0.6%) were followed by a self-harm event within 90 days. Overall classification performance did not differ between the best-fitting model using all data (area under the receiver operating curve or AUC = 0.846, 95% CI 0.839-0.854) and the best-fitting model limited to data available from insurance claims (AUC = 0.846, 95% CI 0.838-0.853). Competing models showed similar classification performance across a range of cut-points and similar calibration performance across a range of risk strata. Results were similar when the sample was limited to health systems and time periods where PHQ-9 depression questionnaires were recorded more frequently. CONCLUSION: Investigators using health record data to account for pre-existing risk in observational studies of suicidal behavior need not limit that research to databases including linked EHR data.

Accurate protamine:heparin matching (not just smaller protamine doses) decreases postoperative bleeding in cardiac surgery; results from a high-volume academic medical center.

BACKGROUND: A multidisciplinary Quality Assurance/Performance Improvement study to identify the incidence of "heparin rebound" in our adult cardiac surgical population instead detected a thromboelastometry pattern suggestive of initial protamine overdose in 34% despite Hepcon-guided anticoagulation management. Analysis of our practice led to an intervention that made an additional lower-range Hepcon cartridge available to the perfusionists. METHODS: One year later, an IRB-approved retrospective study was conducted in >500 patients to analyze the effects of the intervention, specifically focusing on the impact of the initial protamine dose accuracy and 18-h mediastinal chest tube drainage (MCTd). RESULTS: No differences were observed between group demographics, surgical procedures, duration of CPB or perioperative blood product transfusion. Both groups were managed using the same perfusion and anesthesia equipment, strategies, and protocols. The median initial protamine dose decreased by 19% (p < .001) in the intervention group (170 [IQR 140-220] mg; n = 295) versus the control group (210 [180-250] mg; n = 257). Mean 18-h MCTd decreased by 13% (p < .001) in the intervention group (405.15 ± 231.54 mL; n = 295) versus the control group (466.13 ± 286.73 mL; n = 257). Covariate-adjusted mixed effects model showed a significant reduction of MCTd in the intervention group, starting from hour 11 after surgery (group by time interaction p = .002). CONCLUSION: Though previous investigators have associated lower protamine doses with less MCTd, this study demonstrates that more accurately matching the initial protamine dose to the remaining circulating heparin concentration reduces postoperative bleeding.

Heparin Rebound: An In-Depth Review.

The common conception of "heparin rebound" invokes heparin returning to circulation in the postoperative period after apparently adequate intraoperative reversal with protamine. This is believed to portend increased postoperative bleeding and provides the rationale for administering additional empiric doses of protamine in response to prolonged coagulation tests and/or bleeding. However, the relevant literature of the last 60+ years provides only a weak level of evidence that "rebounded" heparin itself is a significant etiology of postoperative bleeding after cardiac surgery with cardiopulmonary bypass. Notably, many of the most frequently cited heparin rebound investigators ultimately concluded that although exceedingly low levels of heparin activity could be detected by anti-Xa assay in some (but not all) patients postoperatively, there was no correlation with actual bleeding. An understanding of the literature requires a careful reading of the details because the investigators lacked standardized definitions for "heparin rebound" and "adequate reversal" while studying the phenomenon with significantly different experimental methodologies and laboratory tests. This review was undertaken to provide a modern understanding of the "heparin rebound" phenomenon to encourage an evidence-based approach to postoperative bleeding. Literature searches were conducted via PubMed using the following MeSH terms: heparin rebound, heparin reversal, protamine, platelet factor 4, and polybrene. Relevant English language articles were reviewed, with subsequent references obtained from the internal citations. Perspective is provided for both those who use HepCon-guided management and those who do not, as are practical recommendations for the modern era based on the published data and conclusions of the various investigators.

Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial.

Importance: Opioids can cause severe respiratory depression by suppressing feedback mechanisms that increase ventilation in response to hypercapnia. Following the addition of boxed warnings to benzodiazepine and opioid products about increased respiratory depression risk with simultaneous use, the US Food and Drug Administration evaluated whether other drugs that might be used in place of benzodiazepines may cause similar effects. Objective: To study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. Design, Setting, and Participants: Randomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021. Interventions: Oxycodone 10 mg on days 1 and 5 and the following in a randomized order for 5 days: paroxetine 40 mg daily, quetiapine twice daily (increasing daily doses from 100 mg to 400 mg), or placebo. Main Outcomes and Measures: Ventilation at end-tidal carbon dioxide of 55 mm Hg (hypercapnic ventilation) using rebreathing methodology assessed for paroxetine or quetiapine with oxycodone, compared with placebo and oxycodone, on days 1 and 5 (primary) and for paroxetine or quetiapine alone compared with placebo on day 4 (secondary). Results: Among 25 participants (median age, 35 years [IQR, 30-40 years]; 11 female [44%]), 19 (76%) completed the trial. The mean hypercapnic ventilation was significantly decreased with paroxetine plus oxycodone vs placebo plus oxycodone on day 1 (29.2 vs 34.1 L/min; mean difference [MD], -4.9 L/min [1-sided 97.5% CI, -∞ to -0.6]; P = .01) and day 5 (25.1 vs 35.3 L/min; MD, -10.2 L/min [1-sided 97.5% CI, -∞ to -6.3]; P < .001) but was not significantly decreased with quetiapine plus oxycodone vs placebo plus oxycodone on day 1 (33.0 vs 34.1 L/min; MD, -1.2 L/min [1-sided 97.5% CI, -∞ to 2.8]; P = .28) or on day 5 (34.7 vs 35.3 L/min; MD, -0.6 L/min [1-sided 97.5% CI, -∞ to 3.2]; P = .37). As a secondary outcome, mean hypercapnic ventilation was significantly decreased on day 4 with paroxetine alone vs placebo (32.4 vs 41.7 L/min; MD, -9.3 L/min [1-sided 97.5% CI, -∞ to -3.9]; P < .001), but not with quetiapine alone vs placebo (42.8 vs 41.7 L/min; MD, 1.1 L/min [1-sided 97.5% CI, -∞ to 6.4]; P = .67). No drug-related serious adverse events were reported. Conclusions and Relevance: In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04310579.

Accuracy of ICD-10-CM encounter diagnoses from health records for identifying self-harm events.

OBJECTIVE: Assess the accuracy of ICD-10-CM coding of self-harm injuries and poisonings to identify self-harm events. MATERIALS AND METHODS: In 7 integrated health systems, records data identified patients reporting frequent suicidal ideation. Records then identified subsequent ICD-10-CM injury and poisoning codes indicating self-harm as well as selected codes in 3 categories where uncoded self-harm events might be found: injuries and poisonings coded as undetermined intent, those coded accidental, and injuries with no coding of intent. For injury and poisoning encounters with diagnoses in those 4 groups, relevant clinical text was extracted from records and assessed by a blinded panel regarding documentation of self-harm intent. RESULTS: Diagnostic codes selected for review include all codes for self-harm, 43 codes for undetermined intent, 26 codes for accidental intent, and 46 codes for injuries without coding of intent. Clinical text was available for review for 285 events originally coded as self-harm, 85 coded as undetermined intent, 302 coded as accidents, and 438 injury events with no coding of intent. Blinded review of full-text clinical records found documentation of self-harm intent in 254 (89.1%) of those originally coded as self-harm, 24 (28.2%) of those coded as undetermined, 24 (7.9%) of those coded as accidental, and 48 (11.0%) of those without coding of intent. CONCLUSIONS: Among patients at high risk, nearly 90% of injuries and poisonings with ICD-10-CM coding of self-harm have documentation of self-harm intent. Reliance on ICD-10-CM coding of intent to identify self-harm would fail to include a small proportion of true self-harm events.

Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis.

OBJECTIVES: To characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016. DESIGN: Individual participant data analysis. POPULATION: 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants. MAIN OUTCOME MEASURES: Responses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models. RESULTS: The random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5% v 9.6%) and less likely to have a Minimal response (12.2.% v 21.5%). CONCLUSIONS: The trimodal response distributions suggests that about 15% of participants have a substantial antidepressant effect beyond a placebo effect in clinical trials, highlighting the need for predictors of meaningful responses specific to drug treatment.

Acute Hyperkinetic Movement Disorders as a Multifactorial Pharmacodynamic Drug Interaction Between Methylphenidate and Risperidone in Children and Adolescents.

PURPOSE/BACKGROUND: Acute hyperkinetic movement disorders have been reported with the concomitant use of attention-deficit/hyperactivity disorder (ADHD) stimulants and antipsychotics in children and adolescents. We analyzed postmarketing reports of suspected acute hyperkinetic movement disorder associated with concomitant use of ADHD stimulants and antipsychotics. METHODS/PROCEDURES: We searched for postmarketing reports of acute hyperkinetic movement disorders associated with concomitant use of ADHD stimulants-antipsychotics in the US Food and Drug Administration Adverse Event Reporting System through December 6, 2019. PubMed and EMBASE were also searched for acute hyperkinetic movement reports with the concomitant use of ADHD stimulants-antipsychotics through January 13, 2020. FINDINGS/RESULTS: We identified 36 cases resulting in acute hyperkinetic movement disorder associated with the concomitant use of ADHD stimulants-antipsychotics, 19 of which were also identified in the medical literature. From an ADHD stimulant perspective, methylphenidate products accounted for the largest number of cases (n = 23 [64%]), followed by amphetamine products (n = 9 [25%]) and atomoxetine (n = 4 [11%]). From an antipsychotic perspective, all 36 cases were reported with second-generation antipsychotics, particularly risperidone (n = 20 [56%]). Most of the cases were reported in boys (n = 31 [86%]) aged 6 to 12 years (n = 27 [75%]). Approximately 53% of the cases reported a time to onset within 24 hours of the drug change. Acute dystonic reactions (n = 27 [75%]) were the most frequently reported movement disorder. IMPLICATIONS/CONCLUSIONS: As outlined in changes to the US prescribing information for all methylphenidate and risperidone products, health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat.

Following a decision to require label warnings for concurrent use of opioids and benzodiazepines and increased risk of respiratory depression and death, the US Food and Drug Administratioin (FDA) recognized that other sedative psychotropic drugs may be substituted for benzodiazepines and be used concurrently with opioids. In some cases, data on the ability of these alternatives to depress respiration alone or in conjunction with an opioid are lacking. A nonclinical in vivo model was developed that could detect worsening respiratory depression when a benzodiazepine (diazepam) was used in combination with an opioid (oxycodone) compared to the opioid alone based on an increased arterial partial pressure of carbon dioxide (pCO2 ). The current study used that model to assess the impact on respiration of non-benzodiazepine sedative psychotropic drugs representative of different drug classes (clozapine, quetiapine, risperidone, zolpidem, trazodone, carisoprodol, cyclobenzaprine, mirtazapine, topiramate, paroxetine, duloxetine, ramelteon, and suvorexant) administered alone and with oxycodone. At clinically relevant exposures, paroxetine, trazodone, and quetiapine given with oxycodone significantly increased pCO2 above the oxycodone effect. Analyses indicated that most pCO2 interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO2 recorded with oxycodone-paroxetine co-administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug-drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co-administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings.

EACTA/SCA Recommendations for the Cardiac Anesthesia Management of Patients With Suspected or Confirmed COVID-19 Infection: An Expert Consensus From the European Association of Cardiothoracic Anesthesiology and Society of Cardiovascular Anesthesiologists With Endorsement From the Chinese Society of Cardiothoracic and Vascular Anesthesiology.

The European Association of Cardiothoracic Anaesthesiology (EACTA) and the Society of Cardiovascular Anesthesiologists (SCA) aimed to create joint recommendations for the perioperative management of patients with suspected or proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing cardiac surgery or invasive cardiac procedures. To produce appropriate recommendations, the authors combined the evidence from the literature review, reevaluating the clinical experience of routine cardiac surgery in similar cases during the Middle East Respiratory Syndrome (MERS-CoV) outbreak and the current pandemic with suspected coronavirus disease 2019 (COVID-19) patients, and the expert opinions through broad discussions within the EACTA and SCA. The authors took into consideration the balance between established procedures and the feasibility during the present outbreak. The authors present an agreement between the European and US practices in managing patients during the COVID-19 pandemic. The recommendations take into consideration a broad spectrum of issues, with a focus on preoperative testing, safety concerns, overall approaches to general and specific aspects of preparation for anesthesia, airway management, transesophageal echocardiography, perioperative ventilation, coagulation, hemodynamic control, and postoperative care. As the COVID-19 pandemic is spreading, it will continue to present a challenge for the worldwide anesthesiology community. To allow these recommendations to be updated as long as possible, the authors provided weblinks to international public and academic sources providing timely updated data. This document should be the basis of future task forces to develop a more comprehensive consensus considering new evidence uncovered during the COVID-19 pandemic.

Guidelines for the Use of Transesophageal Echocardiography to Assist with Surgical Decision-Making in the Operating Room: A Surgery-Based Approach: From the American Society of Echocardiography in Collaboration with the Society of Cardiovascular Anesthesiologists and the Society of Thoracic Surgeons.

Intraoperative transesophageal echocardiography is a standard diagnostic and monitoring tool employed in the management of patients undergoing an entire spectrum of cardiac surgical procedures, ranging from "routine" surgical coronary revascularization to complex valve repair, combined procedures, and organ transplantation. Utilizing a protocol as a starting point for imaging in all procedures and all patients enables standardization of image acquisition, reduction in variability in quality of imaging and reporting, and ultimately better patient care. Clear communication of the echocardiographic findings to the surgical team, as well as understanding the impact of new findings on the surgical plan, are paramount. Equally important is the need for complete understanding of the technical steps of the surgical procedures being performed and the complications that may occur, in order to direct the postprocedure evaluation toward aspects directly related to the surgical procedure and to provide pertinent echocardiographic information. The rationale for this document is to outline a systematic approach describing how to apply the existing guidelines to questions on cardiac structure and function specific to the intraoperative environment in open, minimally invasive, or hybrid cardiac surgery procedures.

Anesthesia teams managing pacemakers and ICDs for the perioperative period: enhanced patient safety and improved workflows.

PURPOSE OF REVIEW: There have been both technological and philosophical advances over the last decade regarding pacemakers and implanted cardioverter defibrillators (ICDs). Collectively, these devices are currently referred to as cardiac implantable electronic devices (CIEDs). Technological advances include the introduction of leadless pacemakers, subcutaneous defibrillators and cardiac event recorders, enhancements regarding compatibility of CIEDs for MRI scanning, the ability to interrogate devices remotely, and improved programming modes that preserve battery life. Philosophical advances have been mainly in the area of perioperative management of CIED patients. RECENT FINDINGS: Current practice recommendations now acknowledge that not every patient requires a formal interrogation of their CIED before and after surgery (as was previously recommended). The response to magnet application is standardized across manufacturer's platforms, and it is known that sources of electromagnetic interference remote from the CIED and its leads do not usually cause any interference with device function. SUMMARY: Educated anesthesia teams can independently manage the vast majority of CIED patients perioperatively with magnet application alone. Furthermore, this portends enhanced patient safety and improved workflows in the perioperative period.

In Search of a Pony: Sources, Methods, Outcomes, and Motivated Reasoning.

It is highly desirable to be able to evaluate the effect of policy interventions. Such evaluations should have expected outcomes based upon sound theory and be carefully planned, objectively evaluated and prospectively executed. In many cases, however, assessments originate with investigators' poorly substantiated beliefs about the effects of a policy. Instead of designing studies that test falsifiable hypotheses, these investigators adopt methods and data sources that serve as little more than descriptions of these beliefs in the guise of analysis. Interrupted time series analysis is one of the most popular forms of analysis used to present these beliefs. It is intuitively appealing but, in most cases, it is based upon false analogies, fallacious assumptions and analytical errors.

Honest Opinion Versus Dishonest Analysis.

Response to the response of Kuldorff and Lu et al.