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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 U.S. Food and Drug Administration (FDA) 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 males (n=31, 86%) aged 6–12 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 U.S. prescribing information for all methylphenidate and risperidone products, healthcare professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.

ImportanceOpioids 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.ObjectiveTo study whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia.Design, Setting, and ParticipantsRandomized, double-blind, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) with 25 healthy participants from January 2021 through May 25, 2021.InterventionsOxycodone 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 MeasuresVentilation 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).ResultsAmong 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 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 P = .67). No drug-related serious adverse events were reported.Conclusions and RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT04310579

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.

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.

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. ispartof: JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA vol:35 issue:7 pages:1953-1963 ispartof: location:United States status: published

This paper is concerned with the poor state or ‘sickness’ of ‘government science’ —a science characterised by its statistical or operational research character, its purported usefulness to government departments in the effective implementation of public policies or projects, and the contracting of the apparently necessary research to agents whose expertise usually exceeds that which is available within a department. The paper refers to cases of ‘sickness’ drawn from the author's own experience, contractual and non-contracted. It pays particular attention to the case of the continuing Safety Camera Partnership Project: its mishandling by the Department of Transport and the consequent level of public concern. The current prevalence of such cases has deep historical roots, going back to the role of Viscount Haldane before the First World War and the neglect of the principles he later formulated. The paper concludes with a practical suggestion for how to avoid ‘sickness’ in any particular project.

Sharma and colleagues essentially duplicate, with more limited data, many of the analyses presented in our 2009 paper but seem not to have read our paper very carefully.1 2 They write, “The FDA did not consider the limitations of the trials that we identified and introduced some of their own—for example, by …

Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults. Design Meta-analysis of 372 double blind randomised placebo controlled trials. Setting Drug development programmes for any indication in adults. Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%). Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation. Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged

Elderly people are particularly at risk of accidents in the home and with an ageing population, they constitute a large proportion of scald victims. We have seen several elderly patients every year in our own unit who had sustained domestic hot water burns. We decided to ascertain the temperature of water in the private homes of elderly people and in residential care homes in our community. Twenty-five private homes and 14 residential care homes were visited and peak water temperatures were measured in the kitchens and bathrooms. Only one private home and one residential home had water below 45 degrees C. It is recommended that water should be delivered at less than 43 degrees C. We conclude that water is dangerously hot. However, if water is stored at a temperature of less than 60 degrees C there is a risk of infection with Legionella pneumophila. Existing regulations governing the use of 'fail safe' thermostatic mixing devices must be enforced and extended to cover domestic hot water systems. Language: en

To the Editor.— In the Jan 17 issue, Avorn and colleagues 1 give valuable evidence of an association of β-blocker and tricyclic antidepressant (TCA) use. In their discussion in the article and in reports in the news media, much emphasis was placed on one explanation: β-blockers cause depression. Their enthusiasm for this explanation is understandable. If correct, the authors have uncovered a large area of preventable morbidity. This enthusiasm may have clouded their consideration of other very plausible explanations. There are a number of ways in which the presence of depression or TCA use would cause physicians to prefer β-blockers. Methyldopa and clonidine have anticholinergic side effects similar to those of tricyclic antidepressants and may add to them. Physicians may have believed other antihypertensive agents to be more likely to cause or aggravate depression than β-blockers and avoided them. Reserpine has a widespread (and possibly unjustified) reputation for causing depression. Clonidine