OBJECTIVE:To review the published data including the pharmacology, efficacy, and safety of seladelpar, a peroxisome proliferator-activated receptor delta (PPARδ) agonist leading to the Food and Drug Administration (FDA) accelerated approval for the treatment of primary biliary cholangitis (PBC). DATA SOURCES:A PubMed (January 1, 1985 to January 27, 2025) literature search was performed using the terms seladelpar, MBX-8025, peroxisome proliferator-activated receptor agonist, and PBC. Other data sources included Google Scholar and the National Institutes of Health Clinical Trials Registry. STUDY SELECTION AND DATA EXTRACTION:All English-language literature evaluating the pharmacology, pharmacokinetics, safety, and efficacy of seladelpar in the treatment of PBC was reviewed. DATA SYNTHESIS:Seladelpar is the first PPARδ agonist in the treatment of PBC that has shown a significant reduction across biochemical response, alkaline phosphatase (ALP) normalization, and pruritus as compared to placebo while demonstrating safety and tolerability.Relevance to patient care and clinical practice in comparison to existing drugs:While existing drug treatments for PBC are efficacious, there remains an unmet need due to an incomplete biochemical response in many patients. Patients frequently suffer from symptoms, including pruritus, impacting their quality of life. Seladelpar could have a beneficial role in PBC as add-on therapy in improving biochemical response as well as alleviating pruritus. CONCLUSION:Seladelpar is a safe and effective treatment for PBC and fills a significant unmet need. Seladelpar's clinical benefit predicted by improvement in surrogate endpoints may need confirmation for traditional FDA approval.

Nearly 42% of adults in the United States are considered obese. Although there are a number of contributing factors to obesity, one sometimes overlooked contributor to weight gain is medications. Within many classes of medications that may affect weight, the degree of weight gain varies. Although factors such as efficacy, cost, interactions, and adverse effects play a role in selecting a medication, the effects on weight also should be considered in those who are overweight or obese. This article reviews some of the classes of medications used in the outpatient setting that may affect weight to provide a guide to clinicians.

PURPOSE:Glucagon-like peptide 1 receptor agonists (GLP1-RA) are effective therapies in lowering glycosylated hemoglobin (HbA1c), providing cardioprotective benefits, and lowering weight. The use of GLP1-RA solely for weight-loss has become commonplace in many practices, which in turn has made it difficult in some areas for those with type 2 diabetes (T2DM) to obtain these much-needed medications. METHODS:Using recent published literature, along with clinical experience, it has become apparent that many GLP1-RAs have become difficult to obtain for patients with diabetes. FINDINGS:Many clinicians started to prescribe the brand Ozempic® (semaglutide*) and dulaglutide for weight loss despite neither of them being Food and Drug Administration (FDA) approved for this indication. Ozempic, having outperformed dulaglutide in in both HbA1c reduction and weight loss, along with FDA approval of semaglutide for weight loss, has quickly become widely used off-label for weight loss. This off-label use may have increased, despite the approval of semaglutide,† because many insurances will not cover semaglutide solely for weight management. Most recently, Eli Lilly was able to develop tirzepatide,‡ which was FDA approved in May of 2022, and they are seeking fast-track FDA approval for weight loss and are projected to gain this approval within 2023. IMPLICATIONS:Insurance coverage for weight management remains sparse, and obtaining these therapies for diabetes has now become more burdensome, with insurance companies requiring a prior authorization proving FDA-approved diagnosis of T2DM. Hopefully, should more GLP1-Ras receive approval for weight loss, along with an increase in insurance coverage, the burden on patients with diabetes will be lessened as they are able to quickly obtain this highly effective therapy.

COVID-19 is known to induce clotting cascade abnormalities, posing challenges in managing warfarin for patients with thromboembolic conditions like atrial fibrillation and pulmonary embolism [1]. Some studies suggest a hypercoagulation state in COVID-19, potentially resulting in a reduced International Normalized Ratio (INR) for patients on warfarin [2]. However, the literature does not conclusively demonstrate a clear association between COVID-19 and fluctuations in the International Normalized Ratio (INR), particularly an increase in INR.

Purpose: The purpose of this study was to examine the effect of initiating use of a continuous glucose monitor (CGM) in patients being treated for type 2 diabetes mellitus, specifically those who face barriers to obtaining this device because of its cost. Methods: This retrospective medical record review compared diabetes control of patients before and after use of a CGM device within a single primary care office. Patient medical records were reviewed 18 months after initial CGM was provided, and only those who received a CGM directly from the clinic were included in the review. Statistical analysis comparing the difference in mean baseline glycosylated hemoglobin (HbA(1c)) level with the first HbA(1c) level after CGM placement was completed using the paired t test for the primary outcome. Findings: A total of 41 patients who obtained at least 1 CGM reader and a minimum of a 30-day supply of sensors from the clinic were included in the review. The primary outcome resulted in a significant reduction in the mean (SD) first HbA(1c) level after CGM placements of - 1.9% ( 2.5%) ( P < .001) with a total of 10 and 22 patients with an HbA(1c) level < 7% and 8%, respectively. This mean (SD) reduction in HbA1c level was also seen in both insulin-treated patients (- 1.8% [ 2.8%], n = 30) and non-insulin-treated patients (- 2% [ 2.8%], n = 11). The largest reduction in the first HbA(1c) level after CGM placement was seen in those patients provided a CGM along with collaborative care with a clinical pharmacist. These patients saw a mean (SD) decrease of - 2.5% [ 2.7%] (n = 26) in their HbA(1c) level with a mean (SD) decrease of - 0.8% ( 1.6%) (n = 15) for those not comanaged by the clinical pharmacist. Implications: The results of this study suggest that the use of CGM in the underserved population can lead to a significant improvement in glycemic control in patients with diabetes, regardless of treatment therapies used. Involving a multidisciplinary team in diabetes management, including clinical pharmacists, may further improve outcomes. Access to these devices in the underserved population may be crucial in reducing the risk of developing complications related to uncontrolled diabetes.

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018-October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

OBJECTIVE:To describe the approval of olanzapine/samidorphan, compare the clinical trial data, and summarize key findings, with a focus on impact to clinical practice.DATA SOURCES:A literature search of PubMed was performed (March 2006 to November 2021) using the following search terms: Lybalvi, olanzapine/samidorphan, olanzapine, antipsychotic, bipolar disorder, and schizophrenia. Product monographs, review articles, and randomized control trials were reviewed.STUDY SELECTION AND DATA EXTRACTION:Relevant English-language studies conducted in humans were considered. Primary use of Phase III clinical drug approval trials preferred; supplementary trial analysis evaluated to provide context.DATA SYNTHESIS:In June 2021, the Food and Drug Administration (FDA) approved Lybalvi® (olanzapine/samidorphan) for indications including treatment of adults with schizophrenia and/or bipolar I disorder (acute manic episodes or acute episodes with mixed features) through the multi-stage ENLIGHTEN clinical trials. Participants were enrolled in 4-week, 24-week, and 52-week studies to evaluate the safety and efficacy of olanzapine/samidorphan. Subsequent secondary analysis evaluated metabolic effects.RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:This review details the pharmacologic, pharmacokinetic, associated dosing and indications, and adverse effects for the drug combination olanzapine/samidorphan. Better understanding of novel drug mechanisms will help to expand on the potential role and place for use in clinical practice.CONCLUSION:When treating complex patients with schizophrenia, the olanzapine/samidorphan combination has limited effect on medication-induced weight gain often associated with antipsychotic olanzapine monotherapy. Additional studies are needed to further define the role of olanzapine/samidorphan in bipolar I disorder and clinical practice.

Objective The purpose of this article is to review the available trials that led to the Food and Drug Administration (FDA) approval of berotralstat, an oral kallikrein inhibitor, for the prevention of hereditary angioedema (HAE) attacks. Data Sources PubMed and ClincalTrials.gov were searched using key term berotralstat to identify phase III clinical trials related to the FDA approval of berotralstat from April 2018 to May 2021. Study Selection and Data Extraction Trials selected were those that influenced the FDA approval of berotralstat or provided novel information regarding the safety and efficacy of this therapy in the treatment of HAE. Data Synthesis Both APeX-2 and ApeX-J found clinically significant benefit with berotralstat 150 mg daily for reduction in HAE attacks when compared with placebo (1.31 vs 2.35, P < 0.001, and 1.11 vs 2.18, P < 0.001, attacks in the APeX-2 and APeX-J trials, respectively). APeX-2 also showed a statistically significant benefit for berotralstat 110 mg daily (1.65 vs 2.35 attacks [1.65 attacks, P = 0.024]). Relevance to Patient Care and Clinical Practice An advantage berotralstat has over the other approved therapies is that it is administered orally, which may garner patient preference because of ease of administration. Berotralstat has also shown a potential benefit in reducing the need for standard-of-care treatment for HAE attacks, which has not been studied with alternative agents. Conclusions Berotralstat 150 mg daily has been proven safe and effective in clinical studies and appears to be a viable oral alternative to parenteral medications currently used in HAE prophylaxis.

PURPOSE:This article discusses the pharmacology of bempedoic acid, the trials that led to United States Food and Drug Administration (FDA) approval of its use, and the overall safety and efficacy of this therapy in heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), and hyperlipidemia.METHODS:A database search of PubMed and ClinicalTrials.gov was conducted for articles published between January 2012 to September 2020 and containing the key words bempedoic acid, ezetimibe, Nexletol and Nexlizet. Trials from the CLEAR series were selected, as they played a pivotal role in the establishment of FDA approval, along with additional trials published after FDA approval, which provided novel evidence on the use of bempedoic acid in the treatment of hypercholesterolemia. Publications that were not randomized, controlled trials were not included in this review. Only randomized controlled trials in which ezetimibe was used in conjunction with bempedoic acid were included in this review as they were relevant to the new FDA approval of bempedoic acid.FINDINGS:The findings of the present review show that bempedoic acid is both an effective and well-tolerated option for the treatment of hypercholesterolemia when used without ezetimibe in addition to standard therapy. It also appears that the combination with ezetimibe increases the cholesterol-lowering effect more than either agent alone when added to standard therapy.IMPLICATIONS:Hypercholesteremia continues to be a major contributing factor leading to ASCVD. Bempedoic acid is an additional treatment option, along with both statins and diet and exercise, for reducing cholesterol levels and ASCVD events. With the new FDA approval, bempedoic acid may offer an effective therapy for reducing low-density lipoprotein cholesterol in patients at high risk for cardiovascular events due to established ASCVD or heterozygous familial hypercholesterolemia.

PURPOSE:Acne vulgaris is a ubiquitous condition in men and women starting in adolescence. It is often persistent and refractory to multiple treatment methods. Although multiple medications may be used on- or off-label for treatment, many adverse effects and risks exist with these treatments, and there has not been an agent with a novel mechanism of action introduced in 40 years. Clascoterone is a recently approved topical acne medication with the first novel mechanism of action since isotretinoin. The purpose of this article was to review the clinical data regarding the safety and efficacy of topical clascoterone for the treatment of acne vulgaris in male and female subjects aged >12 years. METHODS:A literature search of PubMed, EMBASE, and MEDLINE was conducted for clinical trials published between January 2014 and March 2021 in the English language using the key words Winlevi, clascoterone, and acne vulgaris. Articles were selected if they were related to the approval by the US Food and Drug Administration of clascoterone or provided novel data regarding this drug entity. FINDINGS:Two Phase III randomized controlled trials (NCT02608450 and NCT02608476) were ultimately selected, as these trials provided pivotal information to the US Food and Drug Administration for the approval of topical clascoterone. IMPLICATIONS:The findings of this review show that topical clascoterone is likely an effective and safe option for the treatment of acne vulgaris. It offers efficacy rates similar to those of current medications through a novel mechanism of action. Its place in therapy remains unclear, but it might be placed ahead of other androgen receptor antagonists such as spironolactone due to its avoidance of systemic side effects.

The number of babies born extremely low birth weight surviving to be discharged home after experiencing the NICU continues to improve. Unfortunately, early sensory development for these babies occurs in an environment vastly different from the intended in-utero environment and places them at high risk of long-term neurodevelopmental and neurocognitive challenges. Our goal in the NICU must transition from simply discharge home to supporting the neurosensory development necessary for a thriving lifetime. To accomplish a goal of thriving families and thriving babies, it is clear the NICU interprofessional team must share an understanding of neurosensory development, the neuroprotective strategies safeguarding development, the neuropromotive strategies supporting intended maturational development, and the essential nature of family integration in these processes. We share the educational endeavors of 11 center collaboratives in establishing the foundational knowledge necessary to support preterm babies and their families.

OBJECTIVE:The purpose of this article is to review the available clinical trial data that led to the Food and Drug Administration (FDA) approval of solriamfetol as well as its role in clinical practice.DATA SOURCES:A MEDLINE/PubMed search was conducted (January 2000 to February 2020) using the keyword solriamfetol to discover appropriate clinical trials.STUDY SELECTION AND DATA EXTRACTION:Articles were included that were published in the English language and related to the FDA approval of solriamfetol or provided novel information regarding this drug entity.DATA SYNTHESIS:The findings of the review show that solriamfetol may be a safe and effective option for the treatment of excessive sleepiness (ES) related to narcolepsy and obstructive sleep apnea (OSA).RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:Solriamfetol is distinguished from other stimulants in that it has lower binding affinity to dopamine and norepinephrine transporters and does not have the monoamine-releasing effects of amphetamines at usual therapeutic doses. Because of solriamfetol's unique mechanism of action, there may be a reduction in abuse potential compared with the other currently FDA-approved options.CONCLUSIONS:In clinical trials, solriamfetol has shown dose-dependent improvement in wakefulness over placebo and adds another option for clinicians when treating ES in narcolepsy and OSA.

Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.

PURPOSE:There are roughly 30 million Americans diagnosed with diabetes mellitus (DM), with nearly 95% of these cases being type 2 (T2)-DM. The American Diabetes Association continues to recommend metformin as the first-line initial treatment of T2DM, in combination with lifestyle modifications; yet, many require multiple therapies to achieve adequate glycemic control. In patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, adding a glucagon-like peptide 1 receptor agonist is a preferred treatment option; however, many patients are apprehensive about injecting medications. Semaglutide is the first oral option in this life-saving medication class. The purpose of this article was to review the pharmacology, clinical trials, safety profile, along with recommended dosing and costs, of oral semaglutide used for managing patients with T2DM.METHODS:A search through the PubMed, MEDLINE and Cochrane libraries was conducted for literature published from January 2017 through December 2020, using the key word semaglutide. Articles were selected if they were related to the approval of oral semaglutide or provided novel clinical information regarding this drug entity in its oral dosage formulation.FINDINGS:Three Phase II studies of the pharmacokinetic properties and Phase III trials from the PIONEER series were ultimately selected, as these trials were thought to provide pivotal information to the US Food and Drug Administration for the approval of oral semaglutide.IMPLICATIONS:On review of the literature, it appeared that semaglutide is a viable option in treating T2DM. The use of this medication has been associated with glycosylated hemoglobin lowering similar to that with the injectable medication in its same class. Semaglutide was also showed some potential in preventing cardiovascular events as well as increasing weight loss.

The world is suffering a respiratory pandemic disease caused by a novel coronavirus (2019-nCoV), commonly known as COVID-19 (coronavirus disease 2019). The Food and Drug Administration issued an emergency authorization for chloroquine and hydroxychloroquine as experimental treatments for COVID-19 leading to a shortage of both medications. A literature review conducted in April 2020 shows a lack of high-quality data available, resulting in ambiguous guideline recommendations. Decisions to use either drug should be made with careful consideration of risks versus benefits along with proper monitoring. Because of its higher potency and better safety profile, hydroxychloroquine may be the more reasonable treatment option if treatment is initiated.

With continued technologic advances, it is not surprising that gaming techniques are increasingly being used in radiology residency programs. This comprehensive review on gaming in radiology education offers insight into the importance of gaming, types of games and principles utilized in gaming, as well as applications that are inherent in artificial intelligence and continued medical education. The advantages and disadvantages of gaming will be considered, as well as barriers to successful adoption of gaming.

Objective: The purpose of this article is to review the available clinical trial data for andexanet alfa and its role in clinical practice. Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to January 2019) using the keyword andexanet alfa for clinical trials. References of identified articles were searched by hand for additional citations. Study Selection and Data Extraction: We included English-language articles related to the Food and Drug Administration (FDA) approval of andexanet alfa or provided novel information regarding this drug entity. Data Synthesis: The findings of the review show that andexanet alfa may be a safe and effective option for the reversal of apixaban and rivaroxaban. Relevance to Patient Care and Clinical Practice: With the approval of this reversal agent, patients and providers can feel safer when using apixaban and rivaroxaban, which in turn may increase the use of these anticoagulant agents. Conclusions: The new FDA approval of andexanet alfa will allow safer use of oral anticoagulants and will likely further the use of direct oral anticoagulants for anticoagulant needs. Reversing enoxaparin-/edoxaban-induced bleeding with this agent should be limited because there is no FDA approval owing to the fact that only phase II trial data available.

Rationale and objective: Forensic radiology is a relatively unknown subspecialty which is becoming increasingly more important. The field incorporates antemortem and postmortem imaging for the detection and documentation of various pathologies for medicolegal purposes. Postmortem imaging is increasingly used in conjunction with the traditional autopsy in a process called a "virtual" autopsy. Radiography has been a staple of forensic investigations for over a century, first used in 1896. Advanced imaging techniques such as postmortem computed tomography and postmortem magnetic resonance imaging have only recently gained acceptance in the forensic science community. Postmortem computed tomography and postmortem magnetic resonance imaging methods are now widely used in some parts of the world, while other countries including the United States have been slower to adopt these methods into their daily practice. Advanced forensic imaging is increasingly used in the courts where juries have responded positively to such presentation of forensic data. For these reasons, advanced postmortem imaging is becoming a regular part of forensic investigations. The increase in the use of forensic imaging presents a unique opportunity for radiologists to collaborate with pathologists and law enforcement officials. This paper provides an overview of forensic radiology and identifies potential challenges and opportunities.

Objective: The purpose of this article is to review the pharmacological aspects of ertugliflozin and its clinical trials, which led to Food and Drug Administration (FDA) approval for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A MEDLINE/PubMed (May 2013 to October 2018) search was conducted using the following keywords: ertugliflozin, sodium glucose co-transporter 2 inhibitor, SGLT2 inhibitor, type 2 diabetes mellitus, hyperglycemia. Study Selection and Data Extraction Quantify: We included English-language articles evaluating ertugliflozin pharmacology, pharmacokinetics, efficacy, and safety in humans for blood glucose reduction in human subjects. Data Synthesis: Ertugliflozin has been FDA approved and considered both safe and efficacious for the treatment of T2DM with hemoglobin A1C reductions ranging from −0.6% to −1.16%. Safety outcomes appear to be similar to that of other SGLT2 inhibitors. Relevance to Patient Care and Clinical Practice: With this approval, patients and clinicians now have another oral option for treating this difficult disease while minimizing hypoglycemia and other unwanted adverse drug reactions. Conclusions: With the number of patients with diabetes growing, additional safe and effective treatment options available for clinicians and patients is important. Ertugliflozin appears to be an effective and safe therapy as both single and add-on therapy.