These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the recommendations will help to inform clinical decision making for practitioners, and perhaps also serve as a source of information for patients and carers. They are accompanied by a more detailed qualitative review of the available evidence. The strength of supporting evidence for each recommendation is rated.

https://journals.sagepub.com/doi/pdf/10.1177/0269881119889296

Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology:

The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative — Update on progress

Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias.

The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.

Scientific white paper on concentration-QTc modeling

Sudden cardiac death, frequently due to ventricular arrhythmias, is a significant problem globally. Most affected individuals do not arrive at hospital in time for medical treatment. Therefore, there is an urgent need to identify the most-at-risk patients for insertion of prophylactic implantable cardioverter defibrillators. Clinical risk markers derived from electrocardiography are important for this purpose. They can be based on repolarization, including corrected QT (QTc) interval, QT dispersion (QTD), interval from the peak to the end of the T-wave (Tpeak – Tend), (Tpeak – Tend)/QT, T-wave alternans (TWA), and microvolt TWA. Abnormal repolarization properties can increase the risk of triggered activity and re-entrant arrhythmias. Other risk markers are based solely on conduction, such as QRS duration (QRSd), which is a surrogate marker of conduction velocity (CV) and QRS dispersion (QRSD) reflecting CV dispersion. Conduction abnormalities in the form of reduced CV, unidirectional block, together with a functional or a structural obstacle, are conditions required for circus-type or spiral wave re-entry. Conduction and repolarization can be represented by a single parameter, excitation wavelength ( λ = CV × effective refractory period). λ is an important determinant of arrhythmogenesis in different settings. Novel conduction–repolarization markers incorporating λ include Lu e t al. ' index of cardiac electrophysiological balance (iCEB: QT/QRSd), [QRSD× (Tpeak − Tend)/QRSd] and [QRSD × (Tpeak − Tend)/(QRSd × QT)] recently proposed by Tse and Yan. The aim of this review is to provide up to date information on traditional and novel markers and discuss their utility and downfalls for risk stratification.

/pdf/traditional-and-novel-electrocardiographic-conduction-and-31xevhrg0g.pdf

Traditional and novel electrocardiographic conduction and repolarization markers of sudden cardiac death

Block of the hERG potassium channel and prolongation of the QT interval are predictors of drug-induced torsade de pointes. However, drugs that block the hERG potassium channel may also block other channels that mitigate torsade risk. We hypothesized that the electrocardiogram can differentiate the effects of multichannel drug block by separate analysis of early repolarization (global J-Tpeak) and late repolarization (global Tpeak-Tend). In this prospective randomized controlled clinical trial, 22 subjects received a pure hERG potassium channel blocker (dofetilide) and three drugs that block hERG and either calcium or late sodium currents (quinidine, ranolazine, and verapamil). The results show that hERG potassium channel block equally prolongs early and late repolarization, whereas additional inward current block (calcium or late sodium) preferentially shortens early repolarization. Characterization of multichannel drug effects on human cardiac repolarization is possible and may improve the utility of the electrocardiogram in the assessment of drug-related cardiac electrophysiology.

https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2014.155

Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil.

Nurses are facing increased mental health issues, substance use, and even suicide since the novel coronavirus pandemic arrived in the United States. Nurses with substance use disorder (SUD) may enroll in alternative-to-discipline (ATD) programs to retain their license during initial treatment with the goal to return to practice, but this process is not without challenges. For example, previous analyses have shown that the time surrounding disciplinary/regulatory process regarding substance use disorder (SUD) by either employers or licensure boards was a trigger for nurses who died by suicide. Internet searches are a common approach to find information on health-related topics. This limited critical review sought to replicate and evaluate a simple internet search that a nurse seeking information on their state ATD program may complete. Google searches for information on ATD programs were completed on the 50 continental states and Washington, DC between April and September 2022. States with ATD programs were evaluated for evidence-based components and barriers to accessing program information. Publicly available ATD program information ranged from requirements for contact information to obtain details to websites that outline the entire program, including associated costs. While ATD programs offer a significant improvement over traditional disciplinary responses to nurse substance use, a significant barrier is program cost, which can often exclude participation. In this article, we discuss the detailed results of our critical review and offer implications for practice that include opportunities for research and a national database to track ATD program components and target outcomes to support return to practice for nurses with SUDs.

Accessibility and Financial Barriers in the Utilization of Alternative to Discipline Programs in the United States

Support within the nursing community for those coping with substance misuse has been lacking for over a hundred years. A review of the history of substance use disorders in nursing reveals that nurses still encounter similar risks, stigma, and punishments today. Kristin, a nurse for over 30 years, tells her story of trials, tribulations, and triumphs with substance use. She shares how having to face early recovery on her own sparked the development of the Wisconsin Peer Alliance for Nurses (WisPAN). WisPAN offers a community for nurses in recovery to provide peer support to those taking their first steps on the journey toward recovery. 

The Intersection of Nurses With Substance Use Disorder and Peer Support

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Papers

Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil.

Accessibility and Financial Barriers in the Utilization of Alternative to Discipline Programs in the United States

The Intersection of Nurses With Substance Use Disorder and Peer Support