Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy.

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05-8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45-249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04-0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

ChatGPT versus human in generating medical graduate exam multiple choice questions-A multinational prospective study (Hong Kong S.A.R., Singapore, Ireland, and the United Kingdom).

INTRODUCTION: Large language models, in particular ChatGPT, have showcased remarkable language processing capabilities. Given the substantial workload of university medical staff, this study aims to assess the quality of multiple-choice questions (MCQs) produced by ChatGPT for use in graduate medical examinations, compared to questions written by university professoriate staffs based on standard medical textbooks. METHODS: 50 MCQs were generated by ChatGPT with reference to two standard undergraduate medical textbooks (Harrison's, and Bailey & Love's). Another 50 MCQs were drafted by two university professoriate staff using the same medical textbooks. All 100 MCQ were individually numbered, randomized and sent to five independent international assessors for MCQ quality assessment using a standardized assessment score on five assessment domains, namely, appropriateness of the question, clarity and specificity, relevance, discriminative power of alternatives, and suitability for medical graduate examination. RESULTS: The total time required for ChatGPT to create the 50 questions was 20 minutes 25 seconds, while it took two human examiners a total of 211 minutes 33 seconds to draft the 50 questions. When a comparison of the mean score was made between the questions constructed by A.I. with those drafted by humans, only in the relevance domain that the A.I. was inferior to humans (A.I.: 7.56 +/- 0.94 vs human: 7.88 +/- 0.52; p = 0.04). There was no significant difference in question quality between questions drafted by A.I. versus humans, in the total assessment score as well as in other domains. Questions generated by A.I. yielded a wider range of scores, while those created by humans were consistent and within a narrower range. CONCLUSION: ChatGPT has the potential to generate comparable-quality MCQs for medical graduate examinations within a significantly shorter time.

Pushing the limits of low-cost ultra-low-field MRI by dual-acquisition deep learning 3D superresolution.

PURPOSE: Recent development of ultra-low-field (ULF) MRI presents opportunities for low-power, shielding-free, and portable clinical applications at a fraction of the cost. However, its performance remains limited by poor image quality. Here, a computational approach is formulated to advance ULF MR brain imaging through deep learning of large-scale publicly available 3T brain data. METHODS: A dual-acquisition 3D superresolution model is developed for ULF brain MRI at 0.055 T. It consists of deep cross-scale feature extraction, attentional fusion of two acquisitions, and reconstruction. Models for T1 -weighted and T2 -weighted imaging were trained with 3D ULF image data sets synthesized from the high-resolution 3T brain data from the Human Connectome Project. They were applied to 0.055T brain MRI with two repetitions and isotropic 3-mm acquisition resolution in healthy volunteers, young and old, as well as patients. RESULTS: The proposed approach significantly enhanced image spatial resolution and suppressed noise/artifacts. It yielded high 3D image quality at 0.055 T for the two most common neuroimaging protocols with isotropic 1.5-mm synthetic resolution and total scan time under 20 min. Fine anatomical details were restored with intrasubject reproducibility, intercontrast consistency, and confirmed by 3T MRI. CONCLUSION: The proposed dual-acquisition 3D superresolution approach advances ULF MRI for quality brain imaging through deep learning of high-field brain data. Such strategy can empower ULF MRI for low-cost brain imaging, especially in point-of-care scenarios or/and in low-income and mid-income countries.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis.

BACKGROUND: The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. METHODS: PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. RESULTS: Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI -0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI -0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. CONCLUSIONS: This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360433.

Implementation and expansion of inpatient and ambulatory pharmacist credentialing and privileging at an academic medical center.

PURPOSE: This article highlights one academic medical center's effort to implement a complete credentialing and privileging (C&P) process for both inpatient and ambulatory clinical pharmacists. SUMMARY: The C&P process offers a recognized method to advance pharmacy practice. Credentialing is defined as a process whereby an individual is deemed qualified in a specific subject matter area. Privileging is the process whereby an institution grants authority to an individual to perform services based on credentials. Federal guidelines permit pharmacists to obtain the same level of privileges as professional medical staff, such as physicians, if relevant state laws allow for the corresponding pharmacist scope of practice. States establish laws and regulations that specify the scope of practice for various types of licensed healthcare professionals, including pharmacists. Many health systems have attempted pharmacist C&P practices in both the inpatient and ambulatory care setting with varying degrees of success and reach. Privileged pharmacists provide established benefits and value to other members of the healthcare team. Oregon Health & Science University (OHSU) pursued C&P for both inpatient and ambulatory clinical pharmacists. Initiation and implementation processes were complex and accompanied by a variety of challenges. CONCLUSION: OHSU operates with advanced pharmacy practice integrated into the interdisciplinary patient care team. Pharmacist C&P allows pharmacists to demonstrate significant clinical benefits and quality improvement in patient care delivery in both inpatient and ambulatory settings.

Fatigue-Related Change in Surface Electromyographic Activities of the Perilaryngeal Muscles.

PURPOSE: This study set out to quantify the fatigue-related changes in surface electromyographic (sEMG) activities of the perilaryngeal muscles following a vocal loading task. METHOD: Thirty-six young healthy participants (M age = 22.4 years) with normal voice performed karaoke singing for at least 100 min. Before the singing task, all participants underwent the sEMG measure and completed a Perceived Vocal Fatigue Score (P-VFS) questionnaire. After the singing task, all participants were immediately measured with the P-VFS again. Half of the participants were then measured for their sEMG immediately after their karaoke singing task, and the other half were given 20 min of rest before undertaking the sEMG measure. The P-VFS and the median frequency (MDF) of the sEMG signals collected from the suprahyoid, infrahyoid, and sternocleidomastoid muscles before and after the singing task were compared using a linear mixed-effects model. RESULTS: All participants reported a perceived vocal fatigue after singing, with a significantly increased P-VFS. Compared with the presinging baseline, the MDF of the sEMG signals in perilaryngeal muscles was significantly lower immediately after the singing task. Such a significant difference was also found after 20 min following the singing task. CONCLUSIONS: The MDF analysis of the sEMG signals could identify and quantify the performance vocal fatigue contributed by perilaryngeal muscles following a vocal loading task. The findings also showed that such fatigue in perilaryngeal muscles, as far as sEMG activities are concerned, can last for at least 20 min.

A low-cost and shielding-free ultra-low-field brain MRI scanner.

Magnetic resonance imaging is a key diagnostic tool in modern healthcare, yet it can be cost-prohibitive given the high installation, maintenance and operation costs of the machinery. There are approximately seven scanners per million inhabitants and over 90% are concentrated in high-income countries. We describe an ultra-low-field brain MRI scanner that operates using a standard AC power outlet and is low cost to build. Using a permanent 0.055 Tesla Samarium-cobalt magnet and deep learning for cancellation of electromagnetic interference, it requires neither magnetic nor radiofrequency shielding cages. The scanner is compact, mobile, and acoustically quiet during scanning. We implement four standard clinical neuroimaging protocols (T1- and T2-weighted, fluid-attenuated inversion recovery like, and diffusion-weighted imaging) on this system, and demonstrate preliminary feasibility in diagnosing brain tumor and stroke. Such technology has the potential to meet clinical needs at point of care or in low and middle income countries.

Effectiveness of a Two-Tier Family-Oriented Intervention in Enhancing the Family Functioning and Care Capacity of the Family Caregivers of Stroke Survivors: Protocol for a Randomized Controlled Trial.

BACKGROUND: Stroke has profound impacts on families. Often, family members, including stroke survivors and the person who takes up the role of the primary caregiver, would encounter demands on finances, rehabilitation arrangement, and even conflicts. Hence, a family-oriented intervention is expected to enable families to rebuild internal and external resources to achieve optimal rehabilitation and community reintegration. OBJECTIVE: This study aims to describe a design of a two-tier family-oriented care management intervention for enhancing the family functioning and care capacity of the caregivers of stroke survivors. METHODS: The two-tier care management intervention was guided by a standardized protocol conducted by trained professional care managers (first tier) with the support of trained volunteers (second tier), which lasted for 8-12 weeks. Participants were recruited through collaborating hospitals according to inclusion and exclusion criteria. In order to examine the effectiveness and cost-effectiveness of the two-tier care management intervention, a two-arm randomization multicenter study was designed, including an active comparison group, which was guided by a standardized protocol conducted by trained volunteers. Dyadic participants, including both stroke survivors and their primary caregivers for both groups, were invited to participate in a questionnaire survey using standardized and purposefully developed measures 3 times: before the intervention, immediately after the intervention, and 2 months after the intervention. The primary outcome was family functioning measured by the Family Role Performance Scale and Family Assessment Device-General Functioning Scale. The secondary outcomes included caregiving burden, depressive symptoms, care management strategies, and the incremental cost-effectiveness ratio. RESULTS: Recruitment began in January 2017 and was completed at the end of April 2019. Data collection was completed at the end of March 2020. As of March 2020, enrollment has been completed (n=264 stroke caregivers). A total of 200 participants completed the baseline questionnaires. We aim to publish the results by mid-2021. CONCLUSIONS: This study successfully developed a two-tier care management protocol that aims to enhance the family functioning of the caregivers of stroke survivors. Guided by a standardized protocol, this family-oriented two-tier intervention protocol was found to be feasible among Chinese families. TRIAL REGISTRATION: ClinicalTrials.gov NCT03034330; https://ichgcp.net/clinical-trials-registry/NCT03034330. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/16703.

Utilising animal models to evaluate oseltamivir efficacy against influenza A and B viruses with reduced in vitro susceptibility.

The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the efficacy of OST against these viruses in vivo is not well understood. In this study, a ferret model was utilised to evaluate OST efficacy against circulating influenza A and B viruses with a range of in vitro generated 50% inhibitory concentrations (IC50) values for OST. OST efficacy against an A(H1N1)pdm09 and an A(H1N1)pdm09 virus with the H275Y substitution in neuraminidase was also tested in the macaque model. The results from this study showed that OST had a significant impact on virological parameters compared to placebo treatment of ferrets infected with wild-type influenza A viruses with normal IC50 values (~1 nM). However, this efficacy was lower against wild-type influenza B and other viruses with higher IC50 values. Differing pathogenicity of the viruses made evaluation of clinical parameters difficult, although some effect of OST in reducing clinical signs was observed with influenza A(H1N1) and A(H1N1)pdm09 (H275Y) viruses. Viral titres in macaques were too low to draw conclusive results. Analysis of the ferret data revealed a correlation between IC50 and OST efficacy in reducing viral shedding but highlighted that the current WHO guidelines/criteria for defining normal, reduced or highly reduced inhibition in influenza B viruses based on in vitro data are not well aligned with the low in vivo OST efficacy observed for both wild-type influenza B viruses and those with reduced OST susceptibility.

Expanding pharmacy practice through the use of pharmacy technicians as process navigators to facilitate patient access of oral anticancer agents.

OBJECTIVES: Over the past 20 years, there has been an increase in the number of Food and Drug Administration-approved oral anticancer agents. Treatment with the use of these medications can offer patients many benefits, including increased convenience and improved quality of life. However, oral anticancer therapies are associated with significant challenges, including cost and difficulties in obtaining the medication. SETTING: Oncology pharmacists and nurses at the Seattle Cancer Care Alliance oversaw the entire process of oral anticancer therapies, from obtaining signatures and insurance authorization to completing patient education and sending the prescription to the preferred pharmacy. This often led to duplicative efforts and challenges with communication amongst all the team members. PRACTICE DESCRIPTION: The pharmacy department piloted a trained pharmacy technician who was provided the role of process navigator to facilitate and coordinate the entire insurance authorization and patient assistance process involved in obtaining access to oral anticancer medications. Before implementation of the program, the average time spent in total for each oral anticancer prescription was 45.8 minutes for the clinic nurses, 21.8 minutes for the clinical pharmacists, and 45.8 minutes for the pharmacy billing technicians. There was an 89.7% success rate in obtaining these medications for patients. RESULTS: After implementation of this program, the pharmacy technician serving as the process navigator significantly improved efficiency and required an average of 59.5 minutes to complete the same steps, compared with 114 minutes before implementation. After program implementation, it was also observed that the pharmacist and nurse were spending much less time on the insurance authorization process. After implementation of this new role, the success rate of obtaining oral anticancer medications increased to 93.1%. CONCLUSION: This innovative initiative expanded the scope of practice for pharmacy technicians and enabled the other team members to spend time on more clinical activities.

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer.

OBJECTIVE: To review the pharmacology, efficacy, and safety of the cyclin-dependent kinase (CDK) inhibitor, abemaciclib, in the treatment of advanced or metastatic breast cancer (MBC). DATA SOURCES: Relevant information was identified through a MEDLINE/PubMed (January 2000 to June 2018) literature search. The new drug application, prescribing information, and abstracts and posters from scientific meetings were also reviewed. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in the English language. Phase 1, 2, and 3 studies evaluating the pharmacology, efficacy, or safety of abemaciclib for breast cancer were included. DATA SYNTHESIS: Abemaciclib is an oral, potent, small molecule inhibitor of CDK4 and CDK6 activity, which blocks retinoblastoma tumor suppressor protein phosphorylation and thereby prevents progression through the cell cycle. Three major clinical trials, MONARCH 1, 2, and 3, established the efficacy and safety of abemaciclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or MBC. In these trials, response rates were promising, ranging from 19.7% to 59%, and median progression-free survival was significantly prolonged over the control arm in 2 of the trials. Common adverse effects included diarrhea, neutropenia, nausea, abdominal pain, infections, and fatigue. Relevance to Patient Care and Clinical Practice: Although no head-to-head studies have been completed between the CDK4/6 inhibitors, abemaciclib may be an attractive option because of its continuous dosing and ability to be used as monotherapy. CONCLUSIONS: Abemaciclib is an effective and well-tolerated treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report.

BACKGROUND: Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors. CASE PRESENTATION: We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance. CONCLUSIONS: This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of "idiopathic" optic neuritis in the Chinese population.