Enhancing clinical drug trial monitoring with blockchain technology.

BACKGROUND: Clinical drug trials are intricate, involving numerous stakeholders, substantial data, and stringent regulations. Traditional systems for recording, storing, and sharing trial data often face data integrity, transparency, security, and interoperability challenges. The utilization of blockchain technology has emerged as a transformative influence in various industries, and its potential within healthcare, particularly in clinical drug trials, is increasingly gaining recognition. METHODS: Blockchain technology presents a decentralized and immutable ledger system that holds promise in effectively addressing these challenges. As the healthcare industry continues its journey of digital transformation, the incorporation of blockchain technology for monitoring clinical drug trials represents a paradigm shift that can result in more reliable, efficient, and transparent trials. RESULTS AND CONCLUSION: This review explores the innovative application of blockchain technology in transforming the monitoring and management of clinical drug trials and provides a comprehensive overview of the possibilities, challenges, and future directions of blockchain-based monitoring in the context of clinical drug trials, contributing to the progress of both blockchain technology and healthcare research practices.

Incorporating Dermatologic Clinical Research Into Private Practice: A Review.

Clinical research is beneficial for the continued progression of medicine and the larger body of scientific knowledge. Clinical research can be incorporated into a range of settings, ranging from larger learning institutions to small private practices. With the need for continued advancement of the development of pharmaceutical interventions as well as other forms of clinical understanding, it is advantageous to create an environment where smaller, private practices feel comfortable and guided in establishing clinical research. It can be difficult to find the best methods to incorporate in-house clinical research. This review aims to address this gap in the literature, making the establishment of clinical trials, specifically clinical drug trials, more accessible in dermatology for private practices.

Reporting on patient's body mass index (BMI) in recent clinical trials for patients with breast cancer: a systematic review.

BACKGROUND: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.

Procedure for Handling and Storage of Onchocerca volvulus Microfilariae Obtained from Skin Snips for Downstream Genetic Work.

WHO and endemic countries target elimination of transmission of Onchocerca volvulus, the parasite causing onchocerciasis. Population genetic analysis of O. volvulus may provide data to improve the evidence base for decisions on when, where, and for how long to deploy which interventions and post-intervention surveillance to achieve elimination. Development of necessary methods and tools requires parasites suitable for genetic analysis. Based on our experience with microfilariae obtained from different collaborators, we developed a microfilariae transfer procedure for large-scale studies in the Democratic Republic of Congo (DRC) comparing safety and efficacy of ivermectin, the mainstay of current onchocerciasis elimination strategies, and moxidectin, a new drug. This procedure is designed to increase the percentage of microfilariae in skin snips suitable for genetic analysis, improve assignment to metadata, and minimize time and materials needed by the researchers collecting the microfilariae. Among 664 microfilariae from South Sudan, 35.7% and 39.5% failed the mitochondrial and nuclear qPCR assay. Among the 576 microfilariae from DRC, 16.0% and 16.7% failed these assays, respectively. This difference may not only be related to the microfilariae transfer procedure but also to other factors, notably the ethanol concentration in the tubes in which microfilariae were stored (64% vs. ≥75%).

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria.

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1 ) and Na+ /K+ pump (INaK ) densities (IK1 0.11 ± 0.03 vs. 0.07 ± 0.03 S mF-1 ; INaK 0.68 ± 0.15 vs. 0.38 ± 26 S mF-1 ; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12 ± 0.02 S mF-1 ) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL , density 0.08 ± 0.03 S mF-1 ). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa ), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13 ± 0.05 S mF-1 ). For short refractoriness, atria with high INa (median density 8.92 ± 2.59 S mF-1 ) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33 ± 1.41 S mF-1 ). In silico drug trials in 800 human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics. KEY POINTS: Atrial fibrillation (AF) maintenance is facilitated by small L-type Ca2+ current (ICaL ) and large inward rectifier K+ current (IK1 ) and Na+ /K+ pump. In severely remodelled left atrium, with low voltage areas (LVA) covering more than 40% of the posterior wall, sustained AF requires higher IK1 and rotors localize in healthy right atrium. For lower LVA extensions, rotors can also anchor to LVA, if the atria present short refractoriness (low ICaL ) Vernakalant is effective in atria presenting long refractoriness (high ICaL ). For short refractoriness, atria with fast Na+ current (INa ) up-regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low INa . The inward currents (ICaL and INa ) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.

Understanding common key indicators of successful and unsuccessful cancer drug trials using a contrast mining framework on ClinicalTrials.gov.

Clinical trials are essential to the process of new drug development. As clinical trials involve significant investments of time and money, it is crucial for trial designers to carefully investigate trial settings prior to designing a trial. Utilizing trial documents from ClinicalTrials.gov, we aim to understand the common characteristics of successful and unsuccessful cancer drug trials to provide insights about what to learn and what to avoid. In this research, we first computationally classified cancer drug trials into successful and unsuccessful cases and then utilized natural language processing to extract eligibility criteria information from the trial documents. To provide explainable and potentially modifiable recommendations for new trial design, contrast mining was applied to discoverhighly contrasted patterns with a significant difference in prevalence between successful (completion with advancement to the next phase) and unsuccessful (suspended, withdrawn, or terminated) groups. Our method identified contrast patterns consisting of combinations of drug categories, eligibility criteria, study organization, and study design for nine major cancers. In addition to a literature review for the qualitative validation of mined contrast patterns, we found that contrast-pattern-based classifiers using the top 200 contrast patterns as feature representations can achieve approximately 80% F1 score for eight out of ten cancer types in our experiments. In summary, aligning with the modernization efforts of ClinicalTrials.gov, our study demonstrates that understanding the contrast characteristics of successful and unsuccessful cancer trials may provide insights into the decision-making process for trial investigators and therefore facilitate improved cancer drug trial design.

Dasiglucagon: A Novel Ready-to-Use Treatment for Severe Hypoglycemia.

OBJECTIVE: To review dasiglucagon, a novel glucagon analogue approved by the Food and Drug Administration (FDA) for treatment of severe hypoglycemia in 2021. DATA SOURCES: A literature search using the PubMed database (current to March 2022) and ClinicalTrials.gov was conducted using the search term dasiglucagon. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical data from English-language clinical trials were included. DATA SYNTHESIS: Dasiglucagon was studied in 3 clinical trials: 1 in patients aged 6 to 17 years and 2 in adults. In all 3 trials, dasiglucagon was found to provide clinically significant benefit in minutes to plasma glucose recovery compared with placebo (10 vs 40, P < 0.001; 10 vs 30, P < 0.001; 10 vs 35, P < 0.0001). Dasiglucagon was also comparable with reconstituted glucagon in plasma glucose recovery time measured from time of administration. The most common adverse events with dasiglucagon were nausea, vomiting, and headache; no serious safety events were observed. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Dasiglucagon is a novel glucagon analogue that is safe and effective for the treatment of severe hypoglycemia, and it is the first to be stable in aqueous solution. This makes dasiglucagon one of only 3 currently available glucagon treatment options that does not require reconstitution prior to administration. CONCLUSIONS: Dasiglucagon offers safe and effective treatment for severe hypoglycemia in patients aged 6 years and older. The stability of dasiglucagon in aqueous solution provides an additional option for emergency glucagon treatment that does not require reconstitution prior to administration.

Review of Ruxolitinib in the Treatment of Atopic Dermatitis.

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of a newly approved topical Janus kinase 1 (JAK) inhibitor, ruxolitinib (RUX), in patients with atopic dermatitis (AD). DATA SOURCES: A literature search was completed May 1, 2022. The term RUX and AD was queried in MEDLINE (PubMed) and EMBASE databases. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed articles written in English and published prior to May 1, 2022 were included. DATA SYNTHESIS: In the phase II clinical trial, more patients treated with 1.5% topical RUX twice a day had a mean percentage improvement in Eczema Area and Severity Index (EASI) scores from baseline to 4 weeks, when compared to vehicle (71.6% vs 15.5%; P < 0.001). In phase III clinical trials, greater percentage of patients who received 0.75% topical RUX (TRuE-AD1 50.0% and TRuE-AD2 39.0%) or 1.5% topical RUX (TRuE-AD1 53.8% and TRuE-AD2 51.3%) achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and had a ≥2-grade improvement from baseline to 8 weeks, when compared to vehicle (TRuE-AD1 15.1% and TRuE-AD2 7.6%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Atopic dermatitis is a highly prevalent long-term inflammatory skin condition. Pruritus is the main contributor of decreased quality of life in patients with AD. Topical RUX inhibits JAK1 and JAK2 producing antiinflammatory and antipruritic effects. Patients experienced a reduction in pruritus within 2 days. This decreased pruritus translated to increased quality of life and less sleep disturbances. CONCLUSION: Data from phase II and III clinical trials in adult patients suggest RUX is an effective and safe therapy for AD.

Systematic Review of Early Phase Pediatric Clinical Pharmacology Trials.

OBJECTIVE: Children have generally been excluded from early-stage clinical trials owing to safety concerns based in social expectations and not data. However, the repositioning of adult therapeutics for pediatric use and the increase in the development of therapies for pediatric only conditions require the participation of children in phase 1-2 trials. Therefore, the aim of this article is to systematically review the history and current state of early phase pediatric clinical pharmacology trials in order to understand safety concerns, trends, and challenges in pediatric trials. METHODS: This review analyzed the nature of early phase pediatric clinical trials conducted for nononcology conditions through a systematic search that was performed for pediatric non-oncologic phase 1 or phase 1-2 drug and vaccine studies in MEDLINE. RESULTS: The data show that the number of early phase pediatric clinical trials is still small relative to adults but has been on the rise in the past decade with relatively few serious adverse effects observed. CONCLUSIONS: The widespread concerns about children's safety when they participate in early phase clinical trials seem disproportionate, based on our findings. The data confirm that these studies can be conducted safely, and that their results can contribute significantly to pediatric pharmacotherapy.

In-silico drug trials for precision medicine in atrial fibrillation: From ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria.

Atrial fibrillation (AF) inducibility, sustainability and response to pharmacological treatment of individual patients are expected to be determined by their ionic current properties, especially in structurally-healthy atria. Mechanisms underlying AF and optimal cardioversion are however still unclear. In this study, in-silico drug trials were conducted using a population of human structurally-healthy atria models to 1) identify key ionic current properties determining AF inducibility, maintenance and pharmacological cardioversion, and 2) compare the prognostic value for predicting individual AF cardioversion of ionic current properties and electrocardiogram (ECG) metrics. In the population of structurally-healthy atria, 477 AF episodes were induced in ionic current profiles with both steep action potential duration (APD) restitution (eliciting APD alternans), and high excitability (enabling propagation at fast rates that transformed alternans into discordant). High excitability also favored 211 sustained AF episodes, so its decrease, through prolonged refractoriness, explained pharmacological cardioversion. In-silico trials over 200 AF episodes, 100 ionic profiles and 10 antiarrhythmic compounds were consistent with previous clinical trials, and identified optimal treatments for individual electrophysiological properties of the atria. Algorithms trained on 211 simulated AF episodes exhibited >70% accuracy in predictions of cardioversion for individual treatments using either ionic current profiles or ECG metrics. In structurally-healthy atria, AF inducibility and sustainability are enabled by discordant alternans, under high excitability and steep restitution conditions. Successful pharmacological cardioversion is predicted with 70% accuracy from either ionic or ECG properties, and it is optimal for treatments maximizing refractoriness (thus reducing excitability) for the given ionic current profile of the atria.

Hypertrophic cardiomyopathy: an up-to-date snapshot of the clinical drug development pipeline.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a complex cardiac disease with highly variable phenotypic expression and clinical course most often caused by sarcomeric gene mutations resulting in left ventricular hypertrophy, fibrosis, hypercontractility, and diastolic dysfunction. For almost 60 years, HCM has remained an orphan disease and still lacks a disease-specific treatment. AREAS COVERED: This review summarizes recent preclinical and clinical trials with repurposed drugs and new emerging pharmacological and gene-based therapies for the treatment of HCM. EXPERT OPINION: The off-label drugs routinely used alleviate symptoms but do not target the core pathophysiology of HCM or prevent or revert the phenotype. Recent advances in the genetics and pathophysiology of HCM led to the development of cardiac myosin adenosine triphosphatase inhibitors specifically directed to counteract the hypercontractility associated with HCM-causing mutations. Mavacamten, the first drug specifically developed for HCM successfully tested in a phase 3 trial, represents the major advance for the treatment of HCM. This opens new horizons for the development of novel drugs targeting HCM molecular substrates which hopefully modify the natural history of the disease. The role of current drugs in development and genetic-based approaches for the treatment of HCM are also discussed.

Psychedelics: Their Limited Understanding and Future in the Treatment of Chronic Pain.

Psychedelics are hallucinogenic drugs that alter the state of consciousness substantially. They bring about psychological, auditory, and visual changes. The psychedelics act on the brain, implying that they have a powerful psychological impact. One of the main factors contributing to disability worldwide is pain. The majority of people deal with pain on a daily basis. Living with chronic pain affects daily life and has social implications. Chronic pain can be associated with any disease that may be genetic, idiopathic, or traumatic. The standard management of pain is done with pharmacological intervention and physical therapy. However, with time, patients may become resistant to a particular class of drugs. As these drugs do not help in treating the cause of pain, they act by blocking receptors and suppressing nervous systems, as this pharmacological intervention is not a permanent solution for pain management. Long-term use of the pharmacological intervention, which acts by suppressing the nervous system, may develop other side effects on the body. These standard therapies are not as effective in managing pain. The opioid class of drugs has good pain-relieving properties but causes addiction; it needs therapeutic drug monitoring to monitor that it is not abused. Since the first synthetic psychedelic was developed, until today, we have had a fair chance to understand its effects and side effects.​These drugs are very potent and effective. They have shown promising developments in the field of clinical psychology. There is upcoming research on psychedelics' use in treating pain disorders. In this article, let us understand the effect of psychedelic drugs on the brain and body and how they modulate pain. Even today, the precise mechanism of chronic pain is still not understood completely. Psychedelics' application and uses in future medicine and pain management are being studied. Understanding psychedelics' effects on the brain and how they function allows us to link how they might be used to treat chronic pain.

Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology.

BACKGROUND: COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic. METHODS: This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview. RESULTS: A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study. CONCLUSION: The impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

The dynamics of relapses during treatment switch in relapsing-remitting multiple sclerosis.

Based on reported trends in relapse incidence among patients with relapsing-remitting multiple sclerosis, an original model for the response to disease modifying therapies is proposed. With a population approach and separate states for patients accounting for their risk of relapses, a system of nonlinear equations is formulated, similarly to established epidemiological models. Different parameters describe the effect of drugs and treatment switch in reducing the frequency of relapses. The model allows for a good fit to previously published data for experiments where different drugs are used. It also shows that different treatments maintain a high degree of similarity, with analogous dynamical features: a pre-treatment increment in relapse frequency leading to a distinct peak, a rapid drop after treatment switch and a plateau corresponding to a new base relapse activity, which seems dependant on the treatment chosen. A sensitivity analysis shows that the uncertainty in the initial proportions of different populations and the frequency of relapses can modify the overall dynamics of the response to treatment. Drugs are observed to induce effects that depend on patient sample's intrinsic characteristics, producing two clearly distinct and independent dynamics of relapse response. This confirms the clinical observation that certain drugs may be overall more successful in lowering the rate of relapses more significantly than others, notwithstanding the fact that patients behave differently across experiments.

The Impact of Drug Trials With Financial Conflict of Interests on the Meta-analyses: A Meta-epidemiological Study.

BACKGROUND: To assess the impact of trials with potential financial conflict of interests (FCOIs) on evidence synthesis in meta-analyses (MAs). METHODS: A total of 96 MAs from the Cochrane Library about drug trials were investigated. The primary outcomes examined the proportion of conclusions that would change with the exclusion of trials with potential FCOIs. If the proportion of changed conclusions was below the non-inferiority margin of 10%, we considered that it was not inferior to include the trials with potential FCOIs in the MAs. RESULTS: Only 54.17% of MAs reported the funding sources of each included trial, and in 21.88% of MAs, the author-industry-related financial ties of each included trial were reported. When trials with FCOIs were excluded, the changed conclusions of effectiveness and major adverse events were 13.16% and 11.11%, respectively, and the I2 decreased by 13.56% and 10.09%, respectively. For serious adverse events, the exclusion of FCOIs trials did not lead to any change in conclusions; however, the I2 decreased by 24.24%. The impact of trials without reported FCOIs was also examined on evidence synthesis, and the results showed that the changed conclusions of effectiveness and major adverse events were 5.26% and 6.25%, respectively, indicating non-inferiority. However, the I2 increased by 13.60% and 12.37%, respectively. CONCLUSION: In this meta-epidemiological study, we demonstrated that trials with FCOIs may not only influence the final outcome of MAs but may also increase the heterogeneity of results. It is suggested that all MAs fully report the FCOIs involved in evidence-based research and explore the impact of its FCOIs to better provide a more valuable reference for patients, clinicians, and policy-makers.

Two-year efficacy and safety of erenumab in participants with episodic migraine and 2-4 prior preventive treatment failures: results from the LIBERTY study.

OBJECTIVE: To evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2-4 prior preventatives had failed. METHODS: Participants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability. RESULTS: Overall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was -4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain. CONCLUSIONS: Efficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2-4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies. TRIAL REGISTRATION NUMBER: NCT03096834.

Remdesivir and Coronavirus Disease 2019 (COVID-19): Essential Questions and Answers for Pharmacists and Pharmacy Technicians.

Objective: To conduct a review of the investigational drug remdesivir and its therapeutic potential for treatment of COVID-19, in the form of a series of questions and answers. The purpose of the review is to narrow gaps in knowledge, clarify concepts, and to investigate research advancements for health care professionals. Data Sources: From June 2020 to August 2020, we conducted comprehensive searches of MEDLINE-PubMed, Scopus, and Google Scholar databases with no time limitations. Search terms were included that contained the terms "remdesivir," "COVID-19," "novel coronavirus" and "evidence," "therapy," "safety," "effectiveness," "efficacy," "clinical trial." Study Selection and Data Extraction: The sources of information include all publicly available data from previously published research reports. Reports must have at least one reference to remdesivir as a treatment modality for COVID-19 with no specified outcomes. Data Synthesis: Major research findings on the efficacy and safety of remdesivir are summarized in tabular format and presented in chronological order. Results of this review reveal remdesivir to be an effective therapy in specific clinical contexts; however, in several areas, available data are insufficient to support evidence-based guidance for remdesivir in the treatment of COVID-19. Conclusions: Clinical trials on remdesivir are ongoing, yet questions remain and further research is needed as to the selection of patients, effectiveness, and duration of treatment in the use of remdesivir for treatment of COVID-19.

Lasmiditan: Acute Migraine Treatment Without Vasoconstriction. A Review.

Objective: To review the efficacy and safety of the newly Food and Drug Administration approved drug lasmiditan, and its place in therapy in the treatment of acute migraine attacks. Data Sources: A literature search of Web of Science, PubMed, and Google Scholar was preformed (September 1999 to May 2021) using the following search terms: acute migraine treatment, triptans, lasmiditan, Reyvow, Rimegepant, Nurtec, Ubrogepant, Ubrelvy, migraine, vasoconstriction, and cardiovascular risk. Product labeling, https://www.clinicaltriasl.gov, and product monographs were also reviewed. Study Selection and Data Extraction: Relevant English-language studies were considered. Data Synthesis: Lasmiditan is the first in its class approved for acute migraine treatment. Lasmiditan exerts its therapeutic effect through agonism at the 5-HT1F receptor, which has been shown to produce no vasoconstriction in preclinical models. Relevance to Patient Care and Clinical Practice: It is both scientifically and clinically relevant to review lasmiditan and determine the value of an acute migraine drug that does not induce vasoconstriction. Patients with preexisting cardiovascular conditions for which current migraine therapy is contraindicated may benefit from therapeutic use of lasmiditan. However, the potential cardiovascular benefit needs to be weighed against the increased central nervous system risks observed with lasmiditan. Conclusions: Lasmiditan is an oral tablet drug that is used for acute migraine abortive treatment and data suggest that it does not induce vasoconstriction, a common side effect often observed with the current first-line abortive migraine treatment drug class, triptans. This is especially important in acute migraine patients with cardiovascular risk factors in which triptan use is contraindicated.

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD).

Agitation is a common complication of Alzheimer's dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD. We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD. Preliminary findings for 44 participants enrolled thus far show a predominately female, white sample with advanced cognitive impairment (Mini Mental Status Examination mean 7.8) and agitation (Neuropsychiatric Inventory-Clinician Agitation subscale mean 14.1). Adjustments to study design in light of the COVID-19 pandemic are described. Findings from this study will provide guidance for the clinical utility of dronabinol for Agit-AD. ClinicalTrials.gov Identifier: NCT02792257.

Should Deep-Sequenced Amplicons Become the New Gold Standard for Analyzing Malaria Drug Clinical Trials?

Regulatory clinical trials are required to ensure the continued supply and deployment of effective antimalarial drugs. Patient follow-up in such trials typically lasts several weeks, as the drugs have long half-lives and new infections often occur during this period. "Molecular correction" is therefore used to distinguish drug failures from new infections. The current WHO-recommended method for molecular correction uses length-polymorphic alleles at highly diverse loci but is inherently poor at detecting low-density clones in polyclonal infections. This likely leads to substantial underestimates of failure rates, delaying the replacement of failing drugs with potentially lethal consequences. Deep-sequenced amplicons (AmpSeq) substantially increase the detectability of low-density clones and may offer a new "gold standard" for molecular correction. Pharmacological simulation of clinical trials was used to evaluate the suitability of AmpSeq for molecular correction. We investigated the impact of factors such as the number of amplicon loci analyzed, the informatics criteria used to distinguish genotyping "noise" from real low-density signals, the local epidemiology of malaria transmission, and the potential impact of genetic signals from gametocytes. AmpSeq greatly improved molecular correction and provided accurate drug failure rate estimates. The use of 3 to 5 amplicons was sufficient, and simple, nonstatistical criteria could be used to classify recurrent infections as drug failures or new infections. These results suggest AmpSeq is strongly placed to become the new standard for molecular correction in regulatory trials, with potential extension into routine surveillance once the requisite technical support becomes established.