Innovations in clinical neuroscience最新文献

Background: Observations regarding psychostimulant and psychedelic drug-induced psychotic states led to the dopamine, serotonin, and glutamate hypotheses of schizophrenia. Expanding knowledge about the endocannabinoid system and the impact of exogenous cannabinoids on the brain and behavior have elucidated several putative pathways to cannabis-induced psychosis.

Objective: The purpose of the present article was to describe these pathways and propose a cannabinoid hypothesis of schizophrenia.

Main points: The endocannabinoid system was reviewed. Evidence regarding the effect of delta 9-tetrahydrocannabinol (THC) on the brain was described. A connection between cannabis use and first-episode psychosis was elucidated.

Conclusion: Understanding the putative pathways to cannabis-induced psychosis might lead to targeted therapeutic interventions and prevention of schizophrenia in susceptible individuals.

Objective: Extended-release methylphenidate (ER-MPH) formulations used to treat attention deficit hyperactivity disorder (ADHD) have complex pharmacokinetic (PK) profiles, resulting from differing ratios of immediate-release and extended-release components and/or their site of absorption. This study aimed to evaluate the smoothness of PK curves of ER-MPHs.

Design: The integral of the second derivative squared was evaluated for modeled PK curves, with smaller values indicating a smoother curve. The calculated smoothness of each PK curve was normalized by dividing by Cmax 2 to derive a normalized smoothness parameter appropriate across the dose range of each formulation. Calculations used modeled PK curves from 100mg delayed-release and ER-MPH (DR/ER-MPH), 54mg osmotic release oral system MPH (OROS MPH), 60mg MPH controlled-release delivery (MPH CD), 60mg ER-MPH oral suspension (MEROS), 20mg ER dexmethylphenidate (d-MPH ER), and 60mg multilayer-release MPH (MLR-MPH).

Results: The Cmax2-normalized smoothness value was consistent across DR/ER-MPH doses, allowing for relevant comparisons across formulations. Normalized smoothness values differed widely; the lowest normalized smoothness was 0.05 with DR/ER-MPH and ranged up to 9.56 with d-MPH ER.

Conclusion: DR/ER-MPH demonstrated a smoother PK profile compared to the highest dose of other ER-MPH formulations. While the benefits of a smooth PK profile remain to be tested clinically, having fewer peaks and troughs has been hypothesized to reduce waxing and waning of therapeutic effects throughout the day, and more gradual changes in MPH plasma levels have been hypothesized to lower the risk of likeability and potentially abate afternoon symptom rebound.

This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation and other resources offered to health care providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers might provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note: The information and recommendations in this article are applicable to physicians and other health care professionals so "clinician" is used to indicate all treatment team members.

Introduction: Recent reports have shown several cases of cerebrovascular events after vaccination against COVID-19. The effects have been described mainly in women within the first two weeks of receiving the vaccine.

Clinical case: We describe here the first Colombian case of a cerebrovascular event after vaccination against COVID-19 in a 67-year-old woman with a vascular history. Four days after application of the messenger ribonucleic acid (mRNA) vaccine, she exhibited deviation of the labial commissure, ipsilateral ptosis, and limitation of march with lateralization. The event was associated with a subacute ischemic event in the right thalamus in parasagittal situation, changes in chronic ischemic microangiopathy of small vessels, and vascular crossing in the right cerebellar angle, without other alternative causes.

Conclusion: The development and rapid use of vaccines has allowed the hospitalization and mortality statistics associated with COVID-19 to be reduced, but at the same time, it has generated concern about the potential side effects, generating controversy among the general population, especially in individuals with cardiovascular diseases. In our case, we provided evidence for the discussion of potential cerebrovascular events related to the application of vaccines in older people with a history of cerebrovascular diseases. This was done in order to analyze and control in subsequent studies the modulation of medical history on the likely effects of vaccination. However, despite the unavoidable side effects, the benefits of vaccination are superior.

Lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, plus (LGBTQIA+ or LGBTQ+) individuals face a wide array of health disparities both within and separate from the healthcare system. Transgender patients are subject to microaggressions, misgendering, and harassment from providers, medical staff, and fellow patients. These patients experience drastic disparities in suicidality, depression, anxiety, substance use, malignancy, sexually transmitted disease (STD), and victimization of violence. Providers have the opportunity to intervene and positively impact patient experiences through gender-affirming care, but they first require an adequate knowledge base and understanding of the importance of sensitive and inclusive care. Seemingly small interventions, such as listing one's own pronouns, using gender-neutral language, validating and affirming patients, and utilizing appropriate mental and physical health screenings, can lead to significant impacts on the patient experience, health outcomes, and quality of life. This article will discuss some of the most common disparities and obstacles faced by transgender patients and will argue the paramount role of the provider in establishing gender-affirming care and some high-impact avenues which the provider, regardless of specialty, may pursue when caring for these patients.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and tolerability of rituximab (RTX) in comparison to azathioprine (AZT) and mycophenolate mofetil (MMF) for the treatment of NMOSD.

Methods: A systematic search was conducted among electronic databases, including PubMed, Scopus, EBSCO, and Cochrane, for relevant studies. We included randomized, controlled trials and prospective and retrospective studies evaluating the efficacy and safety of RTX compared to AZT and/or MMF in adult and pediatric patients with NMOSD. The Newcastle-Ottawa Scale (NOS) and Cochrane Collaboration tool were used to determine the risk of bias.

Results: Eleven studies involving 1,086 patients were included in our study. Treatment with RTX generally yielded favorable annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) results in comparison to AZT and MMF, despite its variable statistical significance. RTX treatment reduced the relapse rate and hazard risk for relapse (HRR). Patients in the RTX group experienced significantly fewer adverse events, among which the most common were allergies, infections, and leukopenia.

Conclusion: In this study, RTX appeared to be superior to AZT and MMF in improving disability and reducing relapse in patients with NMOSD. RTX is also associated with fewer adverse events based on pooled analysis. Future randomized clinical trials are needed to establish the efficacy and safety of RTX in patients with NMOSD.

Multiple digital health technologies have been evaluated across clinical development programs, including external, wearable, implantable, and ingestible devices and sensors, along with digital mobile health applications (apps) that are accessible via users' personal electronic devices (e.g., smartphones, tablets, and computers). Several of these technologies have been incorporated into our ongoing neurology and respiratory clinical development programs. Based on our experience, one of the greatest potential benefits of digital health technologies is the ability to collect objective and/or biological data continuously or at regular intervals outside of office visits during a patient's normal daily activities to provide additional efficacy and safety information, versus data capture from traditional episodic, time point-based office visits. Many challenges encountered with digital health technologies can be successfully addressed by providing the appropriate training to staff and patients, ensuring availability of appropriate infrastructure support, and conducting pilot studies before scaling up to larger trials. Overall, our experience with digital health technologies demonstrated their potential to increase the amount of objective data collected in clinical trials, expand patient access to trials, and facilitate further improvement of clinical outcomes.

Objective: Lurasidone is a second-generation antipsychotic (SGA) that contributes an antipsychotic and antidepressant effect, with low incidences of metabolic-related diseases and hyperprolactinemia for the treatment of psychological disorders. However, evidence on lurasidone is limited in psychiatric clinical settings. This study aimed to investigate the effect of short-term lurasidone treatment on metabolic effects and prolactin (PRL) levels, in relation to the differences of psychiatric disorders, lurasidone dosages, and introducing methods, in 35 female and 12 male Japanese inpatients with psychiatric disorders.

Methods: Subjects were placed into six subgroups divided by three categories (schizophrenia/schizoaffective disorder or bipolar disorder, 20mg/day or 40mg/day, adding or switching). Sequential changes in 10 items of metabolic parameters, including estimated insulin resistance and PRL levels at one month, were evaluated. The variations of metabolic parameters that were significantly changed from baseline were analyzed against sample characteristics and other metabolic parameter variations.

Results: In the 40mg/day and switching introduction method groups, lurasidone significantly reduced body weight, body mass index (BMI), levels of alanine amiotransaminase, and levels of fasting blood glucose. PRL levels seemed to increase when lurasidone was added and decrease when lurasidone was switched to from other antipsychotics. Switching introduction method and higher dosage correlated with weight loss and lowering fasting blood glucose levels, respectively.

Conclusion: Lurasidone administration offered the potential for weight loss, lowered serum blood glucose levels, and converging serum PRL concentrations. Moreover, switching introduction method with higher dosages might alleviate basal metabolism and glucose homeostasis. Further prospective studies combining measurements of serum insulin and psychometric evaluation will help to confirm our conclusions.