Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated by conducting a systematic review of BZRA deprescribing trials for insomnia, as well as performing a review of reviews of the harms of continued BZRA use and narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality of evidence ratings were used to generate recommendations. The team refined guideline content and recommendations through consensus and synthesized clinical considerations to address front-line clinician questions. The draft guideline was reviewed by clinicians and stakeholders. RECOMMENDATIONS: We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia. CONCLUSION: Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Déprescription des agonistes des récepteurs des benzodiazépines: Lignes directrices de pratique clinique fondées sur les données probantes.

OBJECTIF: Formuler des lignes directrices fondées sur les données probantes visant à aider les cliniciens à décider du moment et de la façon sécuritaire de réduire la dose des agonistes des récepteurs des benzodiazépines (BZRA) pour mettre fin au traitement; se concentrer sur le niveau le plus élevé des données disponibles et obtenir les commentaires des professionnels de première ligne durant le processus de rédaction, de révision et d'adoption des lignes directrices. MÉTHODES: L'équipe comptait 8 cliniciens (1 médecin de famille, 2 psychiatres, 1 psychologue clinique, 1 pharmacologue clinique, 2 pharmaciennes cliniques et 1 gériatre) et une spécialiste de la méthodologie; les membres ont divulgué tout conflit d'intérêts. Nous avons eu recours à un processus systématique, y compris l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour formuler les lignes directrices. Les données ont été générées par une revue systématique d'études portant sur la déprescription des BZRA contre l'insomnie, de même que par une revue des revues sur les torts liés à la poursuite du traitement par BZRA et des synthèses narratives sur les préférences des patients et les répercussions sur les ressources. Ces données et le score GRADE de qualité des données ont servi à formuler les recommandations. L'équipe a peaufiné le texte sur le contenu et les recommandations des lignes directrices par consensus et a synthétisé les considérations cliniques afin de répondre aux questions des cliniciens de première ligne. Une version préliminaire des lignes directrices a été révisée par les cliniciens et les intervenants. RECOMMANDATIONS: Nous recommandons d'offrir la déprescription (réduction lente de la dose) des BZRA à tous les patients âgés (≥ 65 ans) sous un BZRA, sans égard à la durée de l'usage, et suggérons d'offrir la déprescription (réduction lente de la dose) à tous les adultes de 18 à 64 qui prennent un BZRA depuis plus de 4 semaines. Ces recommandations visent les patients qui prennent un BZRA contre l'insomnie seule (insomnie primaire) ou l'insomnie comorbide lorsque les comorbidités sous-jacentes sont efficacement prises en charge. Ces lignes directrices ne visent pas les personnes atteintes d'autres troubles non traités du sommeil ou d'anxiété, de dépression, ou d'autres troubles physiques ou de santé mentale pouvant causer ou aggraver l'insomnie. CONCLUSION: Les agonistes des récepteurs des benzodiazépines sont liés à des torts, et leur effet thérapeutique serait bref. La réduction graduelle de la dose de BZRA améliore le taux d'abandon comparativement aux soins habituels, et ce, sans causer de torts graves. Les patients seraient plus ouverts à une conversation sur la déprescription s'ils comprennent le pourquoi (potentiel de torts), participent à l'élaboration du plan de réduction de la dose et reçoivent des conseils en matière de comportement. Les présentes lignes directrices émettent des recommandations pour décider du moment et de la façon de réduire la dose de BZRA pour mettre fin au traitement. Elles visent à contribuer au processus de décision conjointement avec le patient et non à le dicter.

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.

CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.

The structure of avian polyomavirus reveals variably sized capsids, non-conserved inter-capsomere interactions, and a possible location of the minor capsid protein VP4.

Avian polyomavirus (APV) causes a fatal, multi-organ disease among several bird species. Using cryogenic electron microscopy and other biochemical techniques, we investigated the structure of APV and compared it to that of mammalian polyomaviruses, particularly JC polyomavirus and simian virus 40. The structure of the pentameric major capsid protein (VP1) is mostly conserved; however, APV VP1 has a unique, truncated C-terminus that eliminates an intercapsomere-connecting ß-hairpin observed in other polyomaviruses. We postulate that the terminal ß-hairpin locks other polyomavirus capsids in a stable conformation and that absence of the hairpin leads to the observed capsid size variation in APV. Plug-like density features were observed at the base of the VP1 pentamers, consistent with the known location of minor capsid proteins VP2 and VP3. However, the plug density is more prominent in APV and may include VP4, a minor capsid protein unique to bird polyomaviruses.

An open-label trial of interpersonal psychotherapy in depressed patients with coronary disease.

High rates of depression have been reported in patients with coronary artery disease, and depression has been repeatedly shown to adversely affect cardiac morbidity and mortality. Despite these findings, little work has been devoted to evaluating effective antidepressant treatments for this subpopulation. This open-label trial assessed the efficacy and acceptability of interpersonal psychotherapy in depressed patients with stable coronary artery disease. Seventeen patients with coronary artery disease who met DSM-IV criteria for major depression received 12 weekly sessions of interpersonal psychotherapy. Outcome was assessed with the 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory II. Ten patients received medication during the trial, and seven patients received interpersonal psychotherapy alone. The patients showed a significant reduction in scores on both the Hamilton depression scale and the Beck Depression Inventory II from baseline, with 53% of the patients meeting criteria for remission, as defined by scores of < or =7 and < or =14 on the Hamilton depression scale and the Beck Depression Inventory II, respectively. Medicated and unmedicated patients responded similarly to interpersonal psychotherapy. These data provide support for the potential use of interpersonal psychotherapy in depressed patients with coronary artery disease. The therapy was well tolerated and accepted by patients, with a high proportion achieving remission. Future randomized clinical trials are needed to establish its efficacy.