Mental Health Care Education and Training in Pharmacy Programs in Arabic-Speaking Countries.

OBJECTIVE: This study aimed to assess how entry-level pharmacy programs in Arab countries prepare graduates to provide mental health care, specifically examining the didactic curricula and experiential training in psychiatry in bachelor and PharmD programs. METHODS: An electronic survey was sent to all entry-level pharmacy programs in the 22 Arab countries asking to report on the 2021-2022 academic year. The survey assessed teaching and learning (eg, psychiatric diseases taught and extent of the coverage; contact hours dedicated to psychiatric therapeutics, pharmacology, and medicinal chemistry), experiential training in psychiatry and its challenges, and graduates' preparedness to provide mental health. A descriptive analysis of the data was undertaken, and data were reported for bachelor and PharmD programs separately. RESULTS: Overall, 35 pharmacy programs completed the survey. All PharmD programs and 80% of bachelor programs covered psychiatric therapeutics, and most contact hours were dedicated to pharmacology, followed by psychiatric therapeutics and medicinal chemistry. Over half of the faculty considered that depression and anxiety disorders were covered sufficiently, and 56.2% of programs did not offer experiential training in psychiatry. Common challenges in psychiatry experiential training included a lack of sites and qualified preceptors. Overall, 26.4% of faculty positively rated graduates' preparedness to provide mental health care. Graduates who completed experiential training in psychiatry and PharmD graduates were rated higher. CONCLUSION: Pharmaceutical education in Arab countries could be improved by enhancing the teaching and assessment of mental health topics and expanding psychiatry experiential training. Such changes would improve entry-level pharmacists' competencies in mental health care provision.

Envisioning the Future of Student Success: Report of the 2022-2023 AACP Student Affairs Standing Committee.

Over the past several years, traditional metrics have indicated declining student success within colleges and schools of pharmacy. Though students may be less well-prepared for professional school than in years past, once candidates are admitted to our institutions, we have a responsibility to effectively support their progression through the program. The 2022-2023 Student Affairs Committee was convened to evaluate and advance the construct of student success within Doctor of Pharmacy programs. The Student Affairs Committee was charged with identifying environmental factors affecting the ability of pharmacy students to be successful; determining how colleges and schools of pharmacy are currently meeting needs related to student progress; conducting a literature review to determine what academic support measures minimize attrition; and developing innovative suggestions and recommendations that better support student success. To accomplish this work, we conducted an extensive literature review and synthesis of evidence, engaged in professional networking across the Academy, and administered a wide-ranging student success survey to all colleges and schools of pharmacy. In this report, we explore the complex and interacting systems that affect learning behavior and academic success and offer a novel, comprehensive description of how the Academy is currently responding to challenges of academic and student success. Additionally, we envision the future of student success, offering 7 recommendations to the American Association of Colleges of Pharmacy and 5 suggestions to members of the Academy to advance this vision.

Exploring the Effect of Virtual Education on Student Pharmacists' Confidence toward APPE Readiness.

A drop in confidence in Advanced Pharmacy Practice Experience (APPE) readiness was observed in students in the Class of 2022 prior to starting APPEs. We aim to investigate potential causes of students' low confidence in APPE preparedness to provide solutions and to prevent this outcome with future students. We evaluated students' perceived confidence to start APPEs and compared this to curricular changes, employment obligations, and the impact of COVID-19 on delivery of the pre-APPE and APPE curriculum. Students' low confidence with APPE readiness was not indicative of the following factors: (1) delivery of the didactic curriculum, (2) students' performance in the didactic curriculum, or (3) number of summative assessments in key didactic courses. Rather, the low confidence perception may have been due to differences such as a fully remote didactic experience in the P3 year, more virtual Introductory Pharmacy Practice Experiences (IPPEs), a reduced course load in the P3 spring semester, and changes to a pre-APPE preparatory course compared to other class years. The students' self-reported midpoint scores during their first APPE block and preceptor's evaluations on their performance contrasted their pre-APPE perceptions. Frequent in-person and on-site skills assessments throughout the didactic curriculum seem to reinforce confidence before APPEs.

Predicting the Success of International Pharmacists in a Distance-Based US Doctor of Pharmacy (PharmD) Program: Results from a 5-Year Cohort.

Background: To establish the predictors of success in an international-trained PharmD (ITPD) program between admission criteria and academic performance. Methods: The primary outcome of this study was the correlation of admission criteria with didactic and experiential grade point averages (GPA) for the first 5 years. Candidates meeting the minimum criteria completed a competency exam or the US-Foreign Pharmacy Graduate Equivalency Exam (US-FPGEE). Tests of English language proficiency (TOEFL(R) and ACTFL's Oral Proficiency Interview) plus interview with faculty, students, and alumni were also required. Scores were correlated with both didactic and experiential GPAs. Results: The 23 students admitted to the ITPD program had a cumulative GPA of 3.72. There was a significant correlation between total admissions score and the median pharmacy and healthcare course category GPA (ρ 0.53), but not other categories. The composite TOEFL did not predict any performance but TOEFL writing and speaking did correlate with advanced pharmacy practice experience (APPE) performance. The OPI scores were associated with higher GPAs overall, in advanced integrated clinical sciences, and APPEs. The admission interview scores consistently and significantly correlated with preceptor-rated APPE GPA, practitioner skills, and professionalism (ρ > 0.5; p < 0.05). Performance in early courses significantly predicted the performance in advanced courses and experiential performance (ρ 0.48−0.61). Conclusion: The correlations between early and late course performance demonstrated the cohesiveness of this program. Further study is needed between the predictors of success using non-cognitive admission criteria.

A global assessment of distance pharmacy education amid COVID-19: teaching, assessment and experiential training.

OBJECTIVES: To explore pharmacy colleges' experiences and challenges worldwide with the transition to online teaching during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: From the six World Health Organization regions, 28 countries with the highest number of COVID-19 cases were identified, and 111 pharmacy colleges were randomly selected from these countries. Two online surveys were sent to faculty members and senior administrators. They assessed changes in teaching and learning, experiential training, assessment, readiness for and challenges with distance e-learning and work-related stress. KEY FINDINGS: Data were collected from 46 colleges. The majority (80.4%) of colleges transitioned to distance e-learning. On-site experiential training was discontinued in 55.5% of colleges and 25.0% redesigned on-site training into remote learning experiences. Assessments were modified in 75.9% of colleges. Assuring the integrity of assessments and delivering practical classes were the most prominent faculty challenges. The majority of faculty (75.0%) and administrators (61.9%) reported moderate work-related stress. Nevertheless, most academics felt that they received adequate support from their institutions and had positive perceptions of the transition to distance e-learning during the pandemic. CONCLUSIONS: The COVID-19 pandemic required drastic changes for most programs' teaching methods. Our results showed that educational institutions were somewhat able to support faculty and the needs of educational programs were largely met. However, academic rigour and provision of experiential training can be improved. Faculty emotional support and training needs were not fully addressed in these difficult times. These results shed light on how the global pharmacy academy has addressed the COVID-19 pandemic and help rethink crisis response models.

A longitudinal quality improvement program to optimize experiential education's ability to develop trusted independent pharmacist practitioners.

PROBLEM DESCRIPTION: To meet the evolving role of today's pharmacist, student pharmacists need to be given independent responsibilities that increase in rigor as they advance through the curriculum and be able to practice both autonomously and as part of an interprofessional team. Quality improvement methods: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) experiential programs office undertook a 20-year process of developing independence for students. Students faced increasing challenges and responsibilities as they moved through experiential practice settings, with constant, cyclic adjustments made in response to feedback. RESULTS OF CQI INQUIRY: The continuous focus on developing independence in students has established a culture of trust in the Colorado pharmacy practice community. Students are allowed autonomy, and are challenged with increasing rigor as they advance. Graduates are well-prepared to perform both independently and as part of a team. INTERPRETATION AND DISCUSSION: The curricular framework based on trust and independent learning has helped the SSPPS train student pharmacists to meet the demands of current pharmacy practice, as well as expected roles in the future. Requiring increasing responsibilities from students as they move through the curriculum allows them to move along the spectrum set up through the entrustable professional activity (EPA) assessments to achieve high ratings for an individual skill. Continuous feedback and adjustments are necessary to identify what can be accomplished in pharmacy practice settings. CONCLUSIONS: This 20-year approach to curricular design and modifications within experiential education has produced independent pharmacy practitioners upon graduation.

Leading a Digital Transformation in Pharmacy Education with a Pandemic as the Accelerant.

The global COVID-19 pandemic has not only posed a challenge to education but created an opportunity to spearhead a digital transformation and the novel delivery of a Pharm.D. curriculum. The process to transform the curriculum in a sustainable and iterative manner involved multiple steps including: (1) Communication, (2) Maintaining faculty engagement, (3) Allowing outside the box thinking, (4) Providing resources and tools and (5) Creating accountability and timelines. At our institution, we have been interested in digital transformation since completing our interview of global leaders. We began our journey using the current COVID-19 pandemic as an accelerant for change. Digital transformation in any industry is not a simple undertaking. However, with planning, aligned organizational interests, consistent and regular communication, provision of resources and tools, engaging faculty and creating accountability and timelines with deliverables the implementation can be successful. When the global pandemic wanes and educational institutions commence in-person classes, having undergone the stages of digital transformation, we will be able to embrace these changes and transform education, not having to reproduce pre-pandemic educational systems.

Report of the 2019-2020 AACP Academic Affairs Committee: Developing the Pharmacist Workforce for Society's Medication Use Needs in 2030.

The 2019-2020 Academic Affairs Committee was charged with identifying promising practices in academic-practice partnerships and professional pharmacy organization initiatives that are accelerating the transformation of a workforce prepared to assume responsibility for society's medication use needs in 2030 and determining the role AACP can plan in supporting these partnerships and initiatives. The committee identified a set of ideal principles, characteristics, and design elements of a high-quality, large-scale workforce development program. The committee also categorized current mechanisms for professional workforce development, in addition to identifying their strengths and weaknesses, with the realization that novel approaches are needed to accomplish the goal of large-scale workforce transformation. This report also highlights two existing initiatives aligned with accelerating the transformation of the workforce (ie, the Community Pharmacy Enhanced Services Network (CPESN) ACT (Academia-CPESN Transformation) Pharmacy Collaborative and the American Pharmacists Association ADVANCE platform) and is proposing a policy statement affirming AACP's support. Furthermore, the committee is proposing another policy statement supporting colleges and schools of pharmacy taking an active role in implementing innovative and novel approaches for the development of the current workforce. In order to truly understand the many factors influencing large-scale workforce transformation, the committee is also proposing a stakeholder conference with a wide range of participants and a targeted set of questions focused on current and future needs.

Cultivating a Culture of Reflection Among Pharmacy Students Through Storytelling.

Objective. To hold a storytelling event and assess its effect on Doctor of Pharmacy (PharmD) students' perspectives on and attitudes toward reflection. Methods. Story Slam, a four-hour storytelling competition, was incorporated into the spring semester of the first professional year of a PharmD program. The event featured short first-person stories told by faculty members as well as students. Students were invited to participate in a pre- and post-intervention survey and focus group. An inductive qualitative analysis of the resulting data was conducted using textual and audio artifacts. Results. All 136 first professional year (P1) students participated in the 2019 Story Slam. Eleven students submitted qualitative pre- and post-intervention survey instruments and participated in a semi-structured recorded focus group. Thematic analysis revealed nine themes. Students' perspectives regarding the importance of self-reflection changed after participating in Story Slam, with students expressing a greater willingness to engage in self-reflection in the context of professional practice following the event. Students believed Story Slam created an environment conducive to reflection and engagement, resulting in strengthened relationships with peers and faculty members. Students expressed feeling a wide range of emotions as they shared their story and listened to the stories of others. Conclusion. Story Slam is an effective strategy for introducing P1 students to reflection, while also strengthening the school's reflective culture. Additionally, sharing stories may foster positive relationships and cultivate trust and respect between students and faculty members.

Promoting Interprofessional Team Development in Team-Based Learning (TBL) Through Coaching and the Team Development Measure (TDM).

BACKGROUND: Achieving effective team development for interprofessional Team-Based Learning (TBL) teams requires expansion of the traditional TBL faculty role of 'Guide on the Side' to include the roles of Interprofessional Education (IPE) Promoter and Team Coach as well as longitudinal teaming assessments. ACTIVITY: We describe 1) a novel conceptual framework of TBL faculty roles, 2) the faculty development approach supporting these expanded roles within IPE, and 3) use of the Team Development Measure (TDM). RESULTS: The expanded faculty roles were well received conceptually, faculty development supported role implementation, and TDM assessments demonstrated team improvements. CONCLUSION: An expansion of the traditional TBLfaculty role to include IPE Promotor and Team Coach and the use of longitudinal team assessments successfully supports pre-licensure interprofessional healthcare student teams' development over time.

Curriculum renewal: Alignment of introductory pharmacy practice experiences with didactic course content.

BACKGROUND AND PURPOSE: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) used the opportunity of curriculum renewal to integrate knowledge and skills learned from didactic courses into the introductory pharmacy practice experiences (IPPEs) occurring simultaneously. This paper describes and evaluates the meaningful application of course content into IPPEs, and evaluates the success using qualitative feedback. EDUCATIONAL ACTIVITY AND SETTING: Students entering the renewed curriculum starting in fall 2012 were provided a list of pharmacy skills and activities from didactic course directors that reinforced course content for that semester. The skills and activities were to be completed during the students' IPPE visits in the community or health systems settings, depending on the program year and semester. FINDINGS: Students successfully completed course assignments during their IPPE course program. Not all activities could be completed as designed, and many required modification, including simulated experiences. Feedback from faculty and preceptor members of the school's experiential education committee demonstrated that these activities were valuable and improved learning of course material, but were challenging to implement. DISCUSSION AND SUMMARY: A renewed curriculum that mapped course assignments for completion in experiential settings was successfully established, after some modifications. The program was modified at regular intervals to improve the ability of preceptors to complete these activities in their individual practice environment. A balance between the school providing guidance on what activities students should perform and allowing unstructured independent learning with the preceptor is needed for an optimal experience.

Five years of lesson modification to implement non-traditional learning sessions in a traditional-delivery curriculum: A retrospective assessment using applied implementation variables.

Non-traditional learning (NTL), including aspects of self-directed learning (SDL), may address self-awareness development needs. Many factors can impact successful implementation of NTL. OBJECTIVES: To share our multi-year experience with modifications that aim to improve NTL sessions in a traditional curriculum. To improve understanding of applied implementation variables (some of which were based on successful SDL implementation components) that impact NTL. METHODS: We delivered a single lesson in a traditional-delivery curriculum once annually for five years, varying delivery annually in response to student learning and reaction-to-learning results. At year 5, we compared student learning and reaction-to-learning to applied implementation factors using logistic regression. RESULTS: Higher instructor involvement and overall NTL levels predicted correct exam responses (p=0.0007 and p<0.0001, respectively). Exam responses were statistically equivalent between the most traditional and highest overall NTL deliveries. Students rated instructor presentation skills and teaching methods higher when greater instructor involvement (p<0.0001, both) and lower overall NTL levels (P<0.0001, both) were used. Students perceived that teaching methods were most effective when lower student involvement and higher technology levels (p<0.0001, both) were used. CONCLUSION: When implementing NTL sessions as a single lesson in a traditional-delivery curriculum, instructor involvement appears essential, while the impact of student involvement and educational technology levels varies.

Clinical Pharmacology Research Internships at the Interface between Academia and Industry: Students' Perceptions and Scientific Output.

The Centre for Human Drug Research (CHDR) is a non-profit clinical research institute at the interface between academia and the pharmaceutical industry. CHDR hosts a research internship programme for undergraduate (bio)medical students. The aim of this study was (i) to investigate the student perceptions of the undergraduate research internship and (ii) to quantify the scientific output related to these internships. We surveyed former interns at the CHDR from the year 2007 to 2014 and quantified their scientific output with a PubMed search. There was a response rate to the survey of 61%, with a good overall rating of the internships. Many students considered their internship at CHDR to be (much) more broad (55%) and with a (much) stricter planning (48%), compared to previous internships at academic research groups. In turn, there were many aspects reported to be similar to academic research internships such as focus on research methodology and 'outcome-drivenness'. Twenty-four per cent of the internships resulted in a co-authorship on papers published in peer-reviewed journals with an average impact factor of 3.3. In conclusion, with appropriate management and supervision, effective research electives are possible in the more commercial environment of a clinical research organization.

An Interprofessional Education Panel on Development, Implementation, and Assessment Strategies.

This report provides a primer for implementing interprofessional education (IPE) within pharmacy and health sciences curricula. In 2013, a panel of administrators and faculty members, whose institutions offered IPE, funded by the Josiah Macy Jr. Foundation, shared best collaborative practice models at the American Association of Colleges of Pharmacy (AACP) Annual Meeting. These presenters subsequently collaborated to write a primer as guidance for other institutions interested in successfully implementing and continuously enhancing the quality of IPE programs. In this article, these IPE faculty members provide a rationale for creating IPE reforms, discuss successful strategies for innovative IPE programs, and share lessons learned for implementing effective assessment tools. A structure and process for determining outcomes of IPE models are presented and strategies for exploring shared education opportunities across health professions and for integrating top-down and bottom-up methods for IPE programs are given.

The pharmacologic and clinical effects of medical cannabis.

Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.

Early stage development of the glycine-1 re-uptake inhibitor SCH 900435: central nervous system effects compared with placebo in healthy men.

AIMS: To report the first three studies with SCH 900435, a selective glycine-1 re-uptake inhibitor in development for treating schizophrenia, using systematic evaluations of pharmacodynamics to understand the observed effects. METHODS: Three double-blind, placebo-controlled studies (single, visual effect and multiple dose) were performed. In the single and multiple dose study SCH 900435 (0.5-30 mg) was given to healthy males and frequent pharmacokinetic and pharmacodynamic measurements were performed. The visual effects study incorporated visual electrophysiological measures of macular, retinal and intracranial visual pathway function. RESULTS: In the single dose study (highest difference, 95% CI, P) increases in smooth pursuit eye movements (8, 12 mg (-6.09, 10.14, -2.04, 0.013), 30 mg), pupil : iris ratio (20 and 30 mg (-0.065, 0.09, -0.04, <0.0001)), VAS colour perception (30 mg (-9.48, 13.05, -5.91, <0.0001)) and changes in spontaneous reports of visual disturbance were found, while FSH (8 mg (0.42, 0.18, 0.66, 0.0015), 12, 20 mg), LH (8-30 mg (1.35, 0.65, 2.05, 0.0003)) and EEG alpha2 activity decreased (12, 20, 30 mg (0.27, 0.14, 0.41, 0.0002)). A subsequent dedicated visual effects study demonstrated that visual effects were transient without underlying electrophysiological changes. This provided enough safety information for starting a multiple ascending dose study, showing less visual symptoms after twice daily dosing and titration, possibly due to tolerance. CONCLUSIONS: Several central nervous system (CNS) effects and gonadotropic changes resulted from administration of 8 mg and higher, providing evidence for CNS penetration and pharmacological activity of SCH 900435. Antipsychotic activity in patients, specificity of the reported effects for this drug class and possible tolerance to visual symptoms remain to be established.

Concept-based learning of personalized prescribing.

The variability of drug response in different patients can be caused by various factors including age, change in renal function, co-medication and genotype. Traditionally, these personal variables are considered by clinicians prior to issuing a prescription. This paper provides an overview of a process to individualize prescribing for a patient with an emphasis on how to train (learning) clinicians in skillful rational prescribing. For this purpose the 6STEP methodology, a concept-based learning strategy to achieve a structured therapeutic plan, has been introduced. In contrast to older educational approaches which focused primarily on the drugs or the process of prescribing, the 6STEP is a patient-centred method resulting in individualized therapy. The six interlinked steps provide the (training) prescriber with a structured framework that facilitates a rationalized therapeutic decision by focusing on the individual patient parameters that influence drug response. Educational tools for rational prescribing involve understanding of basic and clinical pharmacological principles, practicing to write 6STEP therapeutic plans, learning from feedback sessions on these plans and actively obtaining up to date information on drugs and therapeutic standards from online resources.

Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Several lines of evidence suggest a possible role of 5-HT(6) receptor antagonists in dementia or cognitive dysfunction of schizophrenia. SB-742457 is a potent 5-HT(6) antagonist and has shown efficacy in different animal models of cognitive impairment. It is currently in development as a cognitive enhancer. Risperidone, commonly used to control agitation and psychotic features in both schizophrenia and Alzheimer's disease, is a D(2)/5-HT(2A ) antagonist with low affinity for 5-HT(6) receptors and limited effects on cognitive parameters. WHAT THIS STUDY ADDS: • As the combination of risperidone and SB-742457 may constitute a reasonable combination in cognitively impaired patients, pharmacodynamic interaction effects were investigated in this study. The only significant drug-drug interaction was a small increase of electroencephalogram (EEG) alpha and beta bands, which might suggest mild arousing activity of SB-742457 on the central nervous system-depressant effects of risperidone. The clinical relevance of these findings in patients remains to be established. Additionally, this study provided an extensive multidimensional pharmacodynamic profile of risperidone in healthy volunteers, showing that this antipsychotic suppresses motor performance (eye-hand coordination, finger tapping and postural stability), alertness, memory and neurophysiological functions (saccadic eye movements and EEG power spectrum). AIM: Several lines of evidence suggest a possible role of 5-HT(6 ) receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT(6) antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS: A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS: Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P= 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P= 0.016). No significant effects of SB-742457 alone were found. CONCLUSION: The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established.