Rimegepant Orally Disintegrating Tablet for Acute Migraine Treatment: A Review.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of rimegepant for treatment of migraine. DATA SOURCES: A comprehensive PubMed and Cochrane search (1985 to May 2020) was performed utilizing the keywords rimegepant, Nurtec, orally disintegrating tablet, migraine, migraine headache, migraine disorder, calcitonin gene-related peptide, and calcitonin gene-related peptide antagonist. Additional data were obtained from the references of identified articles, manufacturer's product labeling and website, ClinicalTrials.gov, and governmental sources. STUDY SELECTION AND DATA EXTRACTION: All English-language trials evaluating oral rimegepant were included for this review. DATA SYNTHESIS: Rimegepant orally disintegrating tablet (ODT) is Food and Drug Administration approved for the treatment of migraine. According to data from 3 phase 3 randomized controlled trials, rimegepant has been shown to significantly improve freedom from pain at 2 hours after the dose and freedom from the most bothersome symptom 2 hours postdose. Additional outcomes improved include freedom from photophobia and phonophobia at 2 hours postdose and pain relief 2 hours after the dose. Adverse effects of rimegepant include nausea, urinary tract infection, and dizziness. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Orally disintegrating rimegepant provides a novel mechanism of action for the treatment of acute migraine. When patients experience inadequate relief from other therapies, have contraindications to triptans, or are unable to tolerate the adverse effects of triptans, rimegepant is a promising therapeutic option. CONCLUSION: Rimegepant ODT is an efficacious migraine treatment option with a novel mechanism of action, convenient dosage form, and limited adverse effect profile.

Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene.

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.

Hummingbird Study: Results from an Exploratory Trial Assessing the Performance and Acceptance of a Digital Medicine System in Adults with Schizophrenia, Schizoaffective Disorder, or First-Episode Psychosis.

PURPOSE: Symptoms of psychotic disorders can complicate efforts to accurately evaluate patients' medication ingestion. The digital medicine system (DMS), composed of antipsychotic medication co-encapsulated with an ingestible sensor, wearable sensor patches, and a smartphone application, was developed to objectively measure medication ingestion. We assessed performance and acceptance of the DMS in subjects with psychotic disorders. METHODS: This was an 8-week open-label, single-arm, multicenter, Phase 4 pragmatic study (NCT03568500; EudraCT #2017-004602-17). Eligible adults were diagnosed with schizophrenia, schizoaffective disorder, or first-episode psychosis; were receiving aripiprazole, quetiapine, olanzapine, or risperidone; and could use the DMS with the application downloaded on a personal smartphone. The primary endpoint was good patch coverage, defined as the proportion of days over the assessment period where ≥80.0% of patch data was available, or an ingestion was detected. Exploratory endpoints included a survey on user satisfaction, used to assess acceptance of the DMS. Safety analyses included the incidence of treatment-emergent adverse events (TEAEs). RESULTS: From May 25, 2018 to March 22, 2019, 55 subjects were screened and 44 were enrolled. Good patch coverage was achieved on 63.4% of days assessed and the DMS generated an adherence metric of ≥80.0%, reflecting the percentage of ingestion events expected when good patch coverage was reported. Most subjects (53.5%) were satisfied with the DMS. Medical device skin irritations were the only TEAEs reported. CONCLUSION: The DMS had sufficient performance in, and acceptance from, subjects with psychotic disorders and was generally well tolerated.

Hummingbird Study: a study protocol for a multicentre exploratory trial to assess the acceptance and performance of a digital medicine system in adults with schizophrenia, schizoaffective disorder or first-episode psychosis.

INTRODUCTION: In patients with schizophrenia, medication adherence is important for relapse prevention, and effective adherence monitoring is essential for treatment planning. A digital medicine system (DMS) has been developed to objectively monitor patient adherence and support clinical decision making regarding treatment choices. This study assesses the acceptance and performance of the DMS in adults with schizophrenia, schizoaffective disorder or first-episode psychosis and in healthcare professionals (HCPs). METHODS/ANALYSIS: This is a multicentre, 8-week, single-arm, open-label pragmatic trial designed using coproduction methodology. The study will be conducted at five National Health Service Foundation Trusts in the UK. Patients 18-65 years old with a diagnosis of schizophrenia, schizoaffective disorder or first-episode psychosis will be eligible. HCPs (psychiatrists, care coordinators, nurses, pharmacists), researchers, information governance personnel, clinical commissioning groups and patients participated in the study design and coproduction. Intervention employed will be the DMS, an integrated system comprising an oral sensor tablet coencapsulated with an antipsychotic, non-medicated wearable patch, mobile application (app) and web-based dashboard. The coencapsulation product contains aripiprazole, olanzapine, quetiapine or risperidone, as prescribed by the HCP, with a miniature ingestible event marker (IEM) in tablet. On ingestion, the IEM transmits a signal to the patch, which collects ingestion and physical activity data for processing on the patient's smartphone or tablet before transmission to a cloud-based server for viewing by patients, caregivers and HCPs on secure web portals or mobile apps. ETHICS AND DISSEMINATION: Approval was granted by London - City and East Research Ethics Committee (REC ref no 18/LO/0128), and clinical trial authorisation was provided by the Medicines and Healthcare products Regulatory Agency. Written informed consent will be obtained from every participant. The trial will be compliant with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines and the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT03568500; EudraCT2017-004602-17; Pre-results.

Pain and the marital relationship: psychiatric distress.

Psychologic assessment and treatment of the family of the chronic pain patient has been thought to be of benefit in the outcome of pain therapy. The present study was designed to determine the presence of psychologic symptoms in the spouses of pain patients and the relationship of distress levels between the marital pair. Forty-four couples were studied. Demographic data was collected and each individual completed the SCL-90, a widely used and validated measure of psychologic symptom severity. There was a significant correlation (P = less than 0.001) on psychiatric distress scores between pain patients and their spouses particularly when pain patient distress scores were high. Distress levels tended to decrease with age and were highest among the unemployed and lowest in the retired. In addition spouses were significantly higher than nonpatient norms on most symptom subscales. These data underline the importance of conjoint assessment of the chronic pain patient and the spouse, and have implications for treatment.

The yin and yang of chromatin spatial organization.

Spatial organization of the genome is non-random. Preferential chromatin interactions, both in cis and in trans and between transcriptionally active and silent regions, influence organization.

Systematic care management: a comprehensive approach to catastrophic injury management applied to a catastrophic burn injury population--clinical, utilization, economic, and outcome data in support of the model.

The new standard for successful burn care encompasses both patient survival and the burn patient's long-term quality of life. To provide optimal long-term recovery from catastrophic injuries, including catastrophic burns, an outcome-based model using a new technology called systematic care management (SCM) has been developed. SCM provides a highly organized system of management throughout the spectrum of care that provides access to outcome data, consistent oversight, broader access to expert providers, appropriate allocation of resources, and greater understanding of total costs. Data from a population of 209 workers' compensation catastrophic burn cases with a mean TBSA of 27.9% who were managed under the SCM model of care were analyzed. The data include treatment type, cost, return to work, and outcomes achieved. Mean duration of management to achieve all guaranteed outcomes was 20 months. Of the 209 injured workers, 152 (72.7%) achieved sufficient recovery to be released to return to work, of which 97 (46.8%) were both released and competitively employed. Assessment of 10 domains of functional independence indicated that 47.2% of injured workers required total assistance at initiation of SCM. However, at termination of SCM, 84% of those injured workers were fully independent in the 10 functional activities. When compared with other burn research outcome data, the results support the value of the SCM model of care.

Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells.

The discovery of interchromosomal interactions in higher eukaryotes points to a functional interplay between genome architecture and gene expression, challenging the view of transcription as a one-dimensional process. However, the extent of interchromosomal interactions and the underlying mechanisms are unknown. Here we present the first genome-wide analysis of transcriptional interactions using the mouse globin genes in erythroid tissues. Our results show that the active globin genes associate with hundreds of other transcribed genes, revealing extensive and preferential intra- and interchromosomal transcription interactomes. We show that the transcription factor Klf1 mediates preferential co-associations of Klf1-regulated genes at a limited number of specialized transcription factories. Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control.