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.

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.

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.

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.

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.

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.

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.

Use of selective serotonin reuptake inhibitors (SSRIs) in women delivering liveborn infants and other women of child-bearing age within the U.S. Food and Drug Administration's Mini-Sentinel program.

This study was conducted in order to assess the prevalence of use of selective serotonin reuptake inhibitors (SSRIs) among pregnant women delivering a liveborn infant in the USA. A retrospective study was conducted using the automated databases of 15 health-care systems participating in the Mini-Sentinel program. Diagnosis and procedure codes were used to identify women ages 10 to 54 years delivering a liveborn infant between April 2001 and December 2013. A comparison group of age- and date-matched women without live births was identified. The frequency of use of SSRIs was identified from outpatient dispensing data. Among the 1,895,519 liveborn deliveries, 113,689 women (6.0 %) were exposed to an SSRI during pregnancy during the period 2001-2013; 5.4 % were exposed to an SSRI during 2013. During the corresponding time period, 10.5 % of the age- and date-matched cohort of women without live births was exposed to an SSRI, with 10.1 % exposed to an SSRI during 2013. The most common agents dispensed during pregnancy were sertraline (n = 48,678), fluoxetine (n = 28,983), and citalopram (n = 20,591). Among those women exposed to an SSRI during pregnancy, 53.8 % had a diagnosis of depression and 37.3 % had a diagnosis of an anxiety disorder during pregnancy or within 180 days prior to pregnancy. Our finding that 6 % of women with live births were prescribed SSRIs during pregnancy highlights the importance of understanding the differential effects of these medications and other therapeutic options on the developing fetus and on the pregnant women.

Novel approaches to spinal cord protection during thoracoabdominal aortic interventions.

PURPOSE OF REVIEW: Spinal cord ischemia after thoracoabdominal aortic interventions is a devastating complication because it significantly worsens the perioperative morbidity and mortality. Long-term outcome is also affected because of medical complications which are directly related to the neural deficits. Paraplegia has significant medical, social, and financial aspects. Limited mobility, the need for assistance in activities of daily living, makes paraplegia an important target for prevention. An understanding of spinal cord blood supply, risk factors for spinal ischemia, and strategies for spinal cord rescue in this setting can help minimize the negative outcome effects of this important complication. RECENT FINDINGS: The vascular supply of the spinal cord is via an extensive collateral arterial network with multiple auxiliary arterial supplies. Risk factors for spinal cord ischemia include extensive aortic repair, prior aortic repair, spinal cord malperfusion on clinical presentation, systemic hypotension, acute anemia, prolonged aortic clamping, and vascular steal. Spinal rescue strategies include systemic hypothermia, endovascular aortic repair, permissive systemic hypertension, cerebrospinal fluid drainage, pharmacologic neuroprotection, and intensive neuromonitoring. SUMMARY: The progression of spinal cord ischemia after thoracoabdominal aortic interventions can frequently be arrested before irreversible infarction results. This spinal cord rescue depends on the early detection and immediate multimodal intervention to maximize spinal cord oxygen supply. The devastating outcomes associated with spinal infarction in this setting offset the risks and knowledge gaps currently associated with contemporary interventions.

Current management of von Willebrand disease and von Willebrand syndrome.

PURPOSE OF REVIEW: Anesthesiologists frequently care for patients with altered hemostasis and coagulation. Where a clear history of familial and personal bleeding exists, a thoughtful plan can be developed in advance to manage the issue perioperatively. However, in some cases, it may not be known that the patient has a disorder until excessive bleeding is noted during or after surgery. Recognition of the issue and appropriate targeted therapy are the keys to successful management. RECENT FINDINGS: With an estimated prevalence approaching 1% of the population, von Willebrand disease (vWD) is the most common hereditary bleeding diathesis, but the estimated prevalence of acquired vWD (often termed von Willebrand syndrome or vWS) is now believed to be significantly higher, especially in patients with malignancies, autoimmune diseases, cardiac valvular lesions, and in patients on mechanical circulatory support devices. Acquired vWD may also occur with certain medications. SUMMARY: The mainstay of the diagnosis of vWD is laboratory testing. Preoperative clinical assessment and a high level of suspicion are often effective to alert the anesthesiologist to the possibility of vWS, thus allowing for appropriate testing and potential prophylaxis in elective situations, as well as appropriately targeted therapy of unexpected bleeding when a hemostatic derangement was not anticipated preoperatively.

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.