Resmetirom: The First Food and Drug Administration-Approved Medication for Nonalcoholic Steatohepatitis (NASH).

OBJECTIVE: To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic steatohepatitis (NASH), including the pharmacology, pharmacokinetics, clinical studies, dosing, and adverse effects. Relevant data will be used to discuss how resmetirom impacts clinical practice. DATA SOURCES: A literature search was conducted using MEDLINE from database inception to May 12, 2024. Keywords included non-alcoholic steatohepatitis, nonalcoholic fatty liver disease, and resmetirom. Study selection, data extraction and all English-language studies involving the use of resmetirom for nonalcoholic fatty liver disease (NAFLD)/NASH were included. DATA SYNTHESIS: Resmetirom, a thyroid hormone receptor agonist, is administered at daily doses of either 80 mg or 100 mg. The drug was shown to provide NASH resolution as assessed by the NAFLD activity score, 80 mg-24.2%, 100 mg-25.9% compared to 14.2% with the placebo group (P < 0.001). Resmetirom, improved liver fibrosis, 80 mg-25.9%, 100 mg-29.9% compared to 9.7% with the placebo group (P < 0.001). Resmetirom's ability to improve fibrosis in patients with F2-F3 fibrosis offers valuable benefit for patients at risk of progressing to cirrhosis. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Resmetirom expands the medication options available to treat patients with NASH which can be given alongside other medications to optimize metabolic factors such as glucagon-like peptide-1 and hydroxymethylglutaryl-coenzyme A reductase inhibitors. Resmetirom was well tolerated in studies. CONCLUSION: Resmetirom serves as an attractive option in patients diagnosed with NASH with evidence of advanced fibrosis (F2-F3) in combination with exercise, diet, and other multimodal therapies targeting metabolic risk factors.

Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene Therapies for Hemophilia A and B.

OBJECTIVE: To review efficacy and safety data of valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparavovec (Hemgenix), novel gene therapies for the treatment of the life-threatening bleeding disorders hemophilia A and B, respectively. DATA SOURCES: A PubMed/Google Scholar search from inception through August 11, 2023 was conducted using the following keywords: gene therapy, hemophilia A, hemophilia B, etranacogene dezaparavovec, valoctocogene roxaparvovec, and bleeding. STUDY SELECTION AND DATA EXTRACTION: Data, including phase 1 to 3 clinical trials (non-comparator), were obtained from primary literature and package inserts. These reports evaluated clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. DATA SYNTHESIS: Valoctocogene phase 3 study in males (n = 134): 87% had factor VIII (FVIII) levels that at least met criteria for mild hemophilia. Etranacogene phase 3 study in males (n = 54): within 3 weeks of infusion, mean factor IX (FIX) levels had reached 26.8 IU/dL. Both therapies provided clinically and statistically significant decreases in bleeding events and prophylactic factor infusions. Most common adverse event was elevations in liver function tests that were treated with glucocorticoids. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: The endogenous production of clotting factors mimics physiological production while decreasing morbidity and mortality related to bleeding events similar to the effects of existing replacement strategies. Gene therapy was also shown to increase patient quality of life. CONCLUSION: Valoctocogene and etranacogene provide another treatment for selected patients with hemophilia. Treatment for the patient with hemophilia (gene therapy vs replacement strategy) must be personalized as new clinical data are published being cognizant of drug affordability.

Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance?

OBJECTIVE: To review the spectrum of activity, efficacy, safety, and role in therapy of all antibiotics and related biologics approved by the Food and Drug Administration (FDA) in the last decade. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2010 to end May 2021) with the search terms' name of the antibiotic or the biologic. Data were also obtained from the prescribing information, FDA, and ClinicalTrials.gov websites. STUDY SELECTION: All relevant English-language, late phase clinical trials assessing the safety and efficacy of the identified drugs were included. Review articles and references of retrieved articles were evaluated for relevant data. DATA SYNTHESIS: Antibiotic resistance is a public health crisis, and antibiotic development is imperative to outpace the ability of bacteria to develop resistance. Only 17 new systemic antibiotics and 1 related biologic have been approved by the FDA since 2010. Among these drugs, 14 were approved for common bacterial infections, 1 was approved for Clostridioides difficile infection (CDI), 1 was licensed to prevent CDI recurrence, and 2 were approved for drug-resistant tuberculosis. Very few antibiotics are in clinical development. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The arrival of these new antibiotics was welcomed with great enthusiasm, particularly when they met previously unmet medical needs. Unfortunately, the majority of them represent modifications to existing chemical structures rather than new drug classes. Despite the availability of these antibiotics, managing patients with deep-seated infections and those with extensively resistant gram-negative organisms remains challenging. CONCLUSIONS: The number of new antibiotics and their indications are not keeping up with resistance and the needs of the patients.

Intravenous Immune Globulin (IVIG) for Treatment of Autoimmune Heparin-Induced Thrombocytopenia: A Systematic Review.

OBJECTIVE: To evaluate intravenous immune globulin (IVIG) for autoimmune heparin-induced thrombocytopenia (aHIT), including platelet recovery, IVIG dose, dosing weight, IVIG product used, and complications reported. DATA SOURCES: PubMed and EMBASE were searched from inception through June 21, 2020. Search terms included heparin-induced thrombocytopenia, HIT, intravenous immune globulin, IVIG, autoimmune HIT, aHIT, and immune globulin. STUDY SELECTION AND DATA EXTRACTION: Patients administered IVIG for HIT and diagnosed by immunoassay (optical density ≥2) or positive activation assay were included. DATA SYNTHESIS: Twenty-four cases were reviewed; 92% had persistent aHIT. Time to IVIG administration post-nonheparin anticoagulant initiation was 9 days (median). Most common IVIG cumulative dose was 2 g/kg (dosed as 1 g/kg/d for 2 consecutive days); 75% had a favorable platelet increase (≥50 × 109/L) within 5 days of initial IVIG dosing. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: aHIT is characterized by critically low platelets, thrombosis, and a persistent delay in platelet recovery despite treatment with a nonheparin anticoagulant. An immunoassay and subsequent confirmatory activation assay (at low, high, and 0 IU/mL unfractionated heparin levels) is recommended to confirm diagnosis. Patients nonresponsive to nonheparin anticoagulants within 5 days of initiation should be evaluated for IVIG treatment (2 g/kg cumulative dose). More data are needed to clarify appropriate IVIG dosing weight, although based on current published literature, it is recommended to use actual body weight. CONCLUSIONS: Data reported support use of IVIG as adjunctive therapy for patients with aHIT. Judicious IVIG use based on key clinical and laboratory findings is critical.

A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease.

OBJECTIVE: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). DATA SOURCES: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. STUDY SELECTION AND DATA EXTRACTION: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. DATA SYNTHESIS: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. CONCLUSIONS: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.

Peanut Allergen Powder-dnfp: A Novel Oral Immunotherapy to Mitigate Peanut Allergy.

OBJECTIVE: To review data on efficacy and safety of peanut allergen powder-dnfp (PAP; Palforzia), a novel oral immunotherapy for peanut allergy, a common food allergy. DATA SOURCES: A PubMed/CINAHL search in English was performed from inception to June 30, 2020, using the search words peanut allergy, desensitization, ARA101, and peanut oral immunotherapy. STUDY SELECTION AND DATA EXTRACTION QUANTIFICATION: Published phase 2 and 3 clinical trials, documents presented to the Food and Drug Administration, and supplemental study documentation were reviewed. Articles evaluated PAP's pharmacology, pharmacokinetics, mechanism of action, efficacy, and safety. DATA SYNTHESIS: PAP was efficacious and safe for treatment of peanut allergy in mostly Caucasian children, 4 to 17 years old. A key phase III clinical trial showed a statistically significant difference (primary end point) between PAP 600 mg and placebo groups (67.2% vs 4%; P < 0.001). During initial dose escalation and updosing phases, gastrointestinal and respiratory tract allergic reactions (ARs) were more common in the PAP group. More epinephrine rescue was used in the PAP group. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Oral immunotherapy for desensitization of peanut allergy was shown to reduce the severity of reactions if accidental allergen exposure occurs. Risk evaluation and mitigation strategy certification is required for pharmacies, health care providers, and clinics. More data in real-world populations will enhance its effectiveness. CONCLUSIONS: In patients 4 to 17 years old, PAP mitigated ARs, including anaphylaxis, that may occur with accidental peanut exposure. Although there are risks, it was efficacious in more than two-thirds of participants in phase 2 and phase 3 efficacy trials.

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease.

OBJECTIVE: To review data on efficacy and safety of osilodrostat (Isturisa), a novel oral steroidogenesis inhibitor for treatment of Cushing's disease (CD), a life-threatening endocrine disorder. DATA SOURCES: A PubMed/CINAHL search from inception to September 25, 2020, was performed using the following keywords: osilodrostat, 11-beta hydroxylase, pituitary, ACTH hypersecretion, and Cushing's disease. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 clinical trials and supplementary documents investigating osilodrostat were obtained from a primary literature search, the manufacturer's website, and the Food and Drug Administration website. These articles evaluated the clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions for osilodrostat. DATA SYNTHESIS: Osilodrostat was efficacious and safe in the treatment of CD in mostly middle-aged Caucasian women. A pivotal phase 3 study revealed a significant difference in 24-hour mean urinary free cortisol (primary end point) between osilodrostat and placebo (86% vs 29%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Osilodrostat provides a potent and consistent effect in reducing life-threatening supraphysiological levels of cortisol in patients with CD. Hypocortisolism adverse effects can be mitigated by slowly increasing osilodrostat's dose at ≥2-week intervals. QT interval prolongation was noted; therefore, the QT interval must be monitored by the electrocardiogram. Increased levels of cortisol precursors during treatment with osilodrostat may increase the risk of hypokalemia, edema, and hypertension. CONCLUSIONS: Osilodrostat was efficacious in decreasing cortisol levels and safe in treating patients who have failed or are ineligible for pituitary surgery. Although risks exist, a pivotal clinical trial revealed efficacy in 86% of participants.

Pulmonary Talaromycosis: A Window into the Immunopathogenesis of an Endemic Mycosis.

Talaromycosis is an invasive mycosis caused by the thermally dimorphic saprophytic fungus Talaromyces marneffei (Tm) endemic in Asia. Like other endemic mycoses, talaromycosis occurs predominantly in immunocompromised and, to a lesser extent, immunocompetent hosts. The lungs are the primary portal of entry, and pulmonary manifestations provide a window into the immunopathogenesis of talaromycosis. Failure of alveolar macrophages to destroy Tm results in reticuloendothelial system dissemination and multi-organ disease. Primary or secondary immune defects that reduce CD4+ T cells, INF-γ, IL-12, and IL-17 functions, such as HIV infection, anti-interferon-γ autoantibodies, STAT-1 and STAT-3 mutations, and CD40 ligand deficiency, highlight the central roles of Th1 and Th17 effector cells in the control of Tm infection. Both upper and lower respiratory infections can manifest as localised or disseminated disease. Upper respiratory disease appears unique to talaromycosis, presenting with oropharyngeal lesions and obstructive tracheobronchial masses. Lower respiratory disease is protean, including alveolar consolidation, solitary or multiple nodules, mediastinal lymphadenopathy, cavitary disease, and pleural effusion. Structural lung disease such as chronic obstructive pulmonary disease is an emerging risk factor in immunocompetent hosts. Mortality, up to 55%, is driven by delayed or missed diagnosis. Rapid, non-culture-based diagnostics including antigen and PCR assays are shown to be superior to blood culture for diagnosis, but still require rigorous clinical validation and commercialisation. Our current understanding of acute pulmonary infections is limited by the lack of an antibody test. Such a tool is expected to unveil a larger disease burden and wider clinical spectrum of talaromycosis.

I ain't afraid of no ghost.

This paper criticizes the traditional philosophical account of the quantization of gauge theories and offers an alternative. On the received view, gauge theories resist quantization because they feature distinct mathematical representatives of the same physical state of affairs. This resistance is overcome by a sequence of ad hoc modifications, justified in part by reference to semiclassical electrodynamics. Among other things, these modifications introduce "ghosts": particles with unphysical properties which do not appear in asymptotic states and which are said to be purely a notational convenience. I argue that this sequence of modifications is unjustified and inadequate, making it a poor basis for the interpretation of ghosts. I then argue that gauge theories can be quantized by the same method as any other theory. On this account, ghosts are not purely notation: they are coordinates on the classical configuration space of the theory-specifically, on its gauge structure. This interpretation does not fall prey to the standard philosophical arguments against the significance of ghosts, due to Weingard. Weingard's argumentative strategy, properly applied, in fact tells in favor of ghosts' physical significance.

Treatment of Depression After Traumatic Brain Injury: A Systematic Review Focused on Pharmacological and Neuromodulatory Interventions.

BACKGROUND: Depression is the most common psychiatric sequela after traumatic brain injury (TBI) and poses a variety of treatment challenges. There is a lack of clinical trials focused on biological interventions used to manage TBI depression. OBJECTIVE: The aim of this systematic review is to summarize the current evidence of psychotropic and neuromodulatory interventions used to treat TBI depression and to provide directions for future research. METHODS: Key words were used to describe the following search terms: "traumatic brain injury", "depression", "pharmacological/drug therapy", and "neuromodulation". Studies focused on pharmacotherapy or neuromodulation in TBI depression were identified in 5 databases: Medline (PubMed), EMBASE (Embase.com), the Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), PsycINFO (EbscoHost), and Web of Science. Article inclusion/exclusion using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic protocol of extraction and evaluation was applied. Level of evidence for each study was determined using the American Academy of Neurology criteria. RESULTS: The initial search provided 1473 citations. Twenty-two studies met inclusion criteria. Sixteen studies explored pharmacological interventions with emphasis on serotonergic agents. Results between studies were conflicting, and interventions did not always outperform placebos, although sertraline provided the highest level of evidence for treatment of TBI depression. Six studies examining neuromodulatory interventions show preliminary evidence of efficacy with a range of interventions and modes of delivery used. CONCLUSIONS: Additional research including large-sample randomized-controlled trials using pharmacological, neuromodulation, or combination treatment is needed. These studies should incorporate premorbid psychosocial functioning, preinjury psychiatric disease, cognitive deficits, and functional recovery when examining outcomes.

Omadacycline: A New Tetracycline Antibiotic.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic. DATA SOURCES: A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer's website were reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical data and published phase 1, 2, and 3 studies were evaluated. DATA SYNTHESIS: Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP. CONCLUSION: Omadacycline is an alternative treatment option for ABSSSI and CABP.

Providing Additional "Muscle" for Older Adults Through Optimal Influenza Vaccine Selection.

Immunization is the best strategy to protect individuals from influenza; however, older adults tend to respond less favorably to vaccines because of immunosenescence. The Centers for Disease Control and Prevention states that any licensed, recommended, and age-appropriate influenza vaccine may be used in older adults despite reasonable evidence suggesting that the high-dose and, to a lesser extent, the adjuvanted and recombinant influenza vaccines provide better protection than the standard-dose vaccines in this vulnerable population. In this era of precision medicine, clinicians can preferentially recommend these contemporary vaccines to equip their older patients with the best possible protection against influenza.

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans.

Risk Assessment Tools for Osteoporosis-Related Fractures.

Osteoporosis is a prevalent and po- tential debilitating disease. Characterized by archi- tectural modifications in bone matrix, osteoporosis ultimatelyincreases the propensity forbones to frac- ture, especially at the hip and spine. Fortunately, osteoporosis can be treated effectively if detected at an early stage. While recognizing an increased risk offracture inwomen with osteoporosis, mostcases of fracture occur in women with osteopenia orlowbone mass. A good fracture risk assessment tool would be more clinically meaningful than an accurate osteo-. porosis screening or diagnostic tool. Here we present a concise review ofthe existing modalities which may be utilized to screen for osteoporosis or predict risk of oteonorotic fractures.

Functional neuroimaging of personally-relevant stimuli in a paediatric case of impaired awareness.

BACKGROUND: Functional neuroimaging studies have observed preserved neural activation to personally relevant stimuli in patients within the disorders of consciousness (DOC) spectrum. As the majority of studies have focused on adult DOC patients, little is known about preserved activation in the developing brain of children with impaired consciousness. CASE STUDY: The aim of this study is to use fMRI to measure preserved neural activation to personally relevant stimuli (subject's own name and familiar voice) in a paediatric patient who sustained a traumatic brain injury and anoxic-ischaemia following a motor vehicle accident at 18 months of age rendering her probable for minimally conscious state. Contrasts revealed activation in the right middle frontal gyrus when hearing the subject's own name and the anterior supramarginal gyrus when hearing a familiar voice. CONCLUSION: This study provides preliminary support for fMRI as a method to measure preserved cognitive functioning in paediatric DOC patients.

A systematic review of cost-effectiveness analyses of gene therapy for hemophilia type A and B.

BACKGROUND: In 2022-2023, the US Food and Drug Administration approved 2 novel gene therapies, valoctocogene roxaparvovec and etranacogene dezaparavovec, for hemophilia A and B, respectively. These one-time-administered gene therapies have been marketed at prices that create financial challenges for payers and patients. Understanding the magnitude and uncertainties around the long-term value of these therapies and how they can potentially relate to managed care practices is of high interest to the payer and patient community. OBJECTIVE: To conduct a systematic review of cost-effectiveness analysis (CEA) studies to assess (1) the long-term value of valoctocogene roxaparvovec and etranacogene dezaparavovec and (2) the relevance and validity of the underlying data and assumptions used in the CEA models and discuss how they relate to the challenges identified for CEAs of gene therapies. METHODS: A systematic review of cost-effectiveness studies of novel hemophilia A and B gene therapy was conducted. PubMed and Embase were searched for published studies from inception to January 12, 2024. Original research articles published in English that conducted a CEA on gene therapy treatments for hemophilia A and B, with a comparison of incremental costs and health effects, were considered. Critical appraisal of the quality of reporting and the underlying modeling assumptions were conducted to assess the relevance and validity of the results. RESULTS: Two hundred thirty-eight studies were identified, of which 4 met the inclusion criteria. Three studies were conducted from a US health care perspective and 1 from a Dutch societal perspective. Despite the high upfront costs of the gene therapies, all included studies' (3 hemophilia A and 1 hemophilia B) modeled results showed that gene therapies had lower overall costs and better health outcomes compared with factor concentrate replacement therapies and emicizumab. The results were driven by the assumption that gene therapies will have a durable effect of at least 10 years and offset the high cost of the current standard of care. The modeled health improvements varied substantially across studies, showing that the long-term value is sensitive to varying clinical and economic assumptions. CONCLUSIONS: The novel hemophilia gene therapy treatments can potentially be a cost-effective use of treatment resources if the treatment effects are durable over time. To reduce the risk for payers while still facilitating patient access, outcomes-based agreements similar to what has recently been proposed by the Centers for Medicare & Medicaid Services for sickle-cell therapies are well supported.

The Interconnectedness of Interprofessional Education and Professional Identity Formation.

Professional identity formation (PIF) is the transformative process by which an individual, "thinks, feels and acts" in accordance with professional norms. In the pharmacy academy, institutions are required to support students on this transformative journey, however the most efficient and effective way to do so has yet to be determined. Interprofessional Education (IPE) in pharmacy programs typically consist of activities and assessments across most of the professional years. These IPE activities designed in accordance with the Interprofessional Education Collaborative (IPEC) Core Competencies include key elements of PIF such as, individual growth opportunities, socialization and "pivotal" moments that can propel an individual's professional identity development. In light of curricular overload and attempt for curricular efficiency, pharmacy programs might consider using already existing IPE programming to help augment student PIF.

Chronic treatment with the serotonin 2A/2C receptor antagonist SR 46349B enhances the retention and efficiency of rule-guided behavior in mice.

Animal studies have established that drugs activating the serotonin 2A (5-HT2A) receptor can enhance learning and memory in a variety of classical and operant conditioning tasks. Unfortunately, long-term agonism typically results in receptor downregulation, which can negate such nootropic effects. Conversely, chronic antagonism can act to increase receptor density, an adaptation which, in principle, should enhance cognition in a manner similar to acute agonism. In this study, we questioned whether chronic treatment with the 5-HT2A receptor antagonist, SR 46349B, a drug known to increase 5-HT2A receptor density in vivo, would improve cognitive performance in normal mice. To address this question, we administered SR 46349B to mice for 4 days following initial training on a simple rule-based reward acquisition task. We subsequently tested their recall of this task and, finally, their ability to adapt to a reversal in reward contingency (reversal learning). For comparison, two additional groups were treated with the 5-HT2A/2C receptor agonist, DOI, which downregulates the 5-HT2A receptor. SR 46349B improved retention of the previously-learned task but did not affect reversal learning. Subjects treated with SR 46349B also completed trials faster and with greater motor efficiency than vehicle- or DOI-treated subjects. We hypothesize that long-term drug treatments resulting in 5-HT2A receptor up-regulation may be useful in enhancing recall of learned behaviors and, thus, may have potential for treating cognitive impairment associated with neurodegenerative disorders.