Serotonin syndrome presenting as acute dizziness with supine hypertension and orthostatic hypotension.

Serotonin syndrome (SS) is a drug-induced clinical syndrome characterised by a combination of cognitive, neuromuscular and autonomic dysfunctions. The symptoms may include mild non-specific symptoms such as tremors and diarrhoea to coma and sudden death. Herein, we describe a case of SS in which acute dizziness was associated with supine hypertension and orthostatic hypotension. A man in his mid-30s had a 10-month history of anxiety, depression and chronic tension-type headache. He had been on amitriptyline (25 mg daily) and sertraline (50 mg daily). Increment of sertraline (75 mg daily) and amitriptyline (75 mg daily) and the addition of tramadol led to the development of acute severe dizziness. Physical examinations demonstrate supine hypertension and orthostatic hypotension. He also met the diagnostic criteria of SS. The administration of cyproheptadine provided a complete response to dizziness, supine hypertension, orthostatic hypotension and other clinical features of SS.

Comparison of side effects of different steroids used in intratympanic injections.

OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Safety and Efficacy of Cenobamate for the Treatment of Focal Seizures in Older Patients: Post Hoc Analysis of a Phase III, Multicenter, Open-Label Study.

BACKGROUND: Cenobamate is an antiseizure medication (ASM) approved in the US and Europe for the treatment of uncontrolled focal seizures. OBJECTIVE: This post hoc analysis of a phase III, open-label safety study assessed the safety and efficacy of adjunctive cenobamate in older adults versus the overall study population. METHODS: Adults aged 18-70 years with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled in the phase III, open-label safety study; adults aged 65-70 years from that study were included in our safety analysis. Discontinuations due to adverse events and treatment-emergent adverse events (TEAEs) were assessed throughout the study in all patients who received one or more doses of cenobamate (safety study population). Efficacy was assessed post hoc in patients who had adequate seizure data available (post hoc efficacy population); we assessed patients aged 65-70 years from that population. Overall, 100% responder rates were assessed in the post hoc efficacy maintenance-phase population in 3-month intervals. Concomitant ASM drug load changes were also measured. For each ASM, drug load was defined as the ratio of actual drug dose/day to the World Health Organization defined daily dose (DDD). RESULTS: Of 1340 patients (mean age 39.7 years) in the safety study population, 42 were ≥ 65 years of age (mean age 67.0 years, 52.4% female). Median duration of exposure was 36.1 and 36.9 months for overall patients and older patients, respectively, and mean epilepsy duration was 22.9 and 38.5 years, respectively. At 1, 2, and 3 years, 80%, 72%, and 68% of patients overall, and 76%, 71%, and 69% of older patients, respectively, remained on cenobamate. Common TEAEs (≥ 20%) were somnolence and dizziness in overall patients, and somnolence, dizziness, fall, fatigue, balance disorder, and upper respiratory tract infection in older patients. Falls in older patients occurred after a mean 452.1 days of adjunctive cenobamate treatment (mean dose 262.5 mg/day; mean concomitant ASM drug load 2.46). Of 240 patients in the post hoc efficacy population, 18 were ≥ 65 years of age. Mean seizure frequency at baseline was 18.1 seizures/28 days for the efficacy population and 3.1 seizures/28 days for older patients. Rates of 100% seizure reduction within 3-month intervals during the maintenance phase increased over time for the overall population (n = 214) and older adults (n = 15), reaching 51.9% and 78.6%, respectively, by 24 months. Mean percentage change in concomitant ASM drug load, not including cenobamate, was reduced in the overall efficacy population (31.8%) and older patients (36.3%) after 24 months of treatment. CONCLUSIONS: Results from this post hoc analysis showed notable rates of efficacy in older patients taking adjunctive cenobamate. Rates of several individual TEAEs occurred more frequently in older patients. Further reductions in concomitant ASMs may be needed in older patients when starting cenobamate to avoid adverse effects such as somnolence, dizziness, and falls. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02535091.

Minimal important difference in postoperative morphine consumption after hip and knee arthroplasty using nausea, vomiting, sedation and dizziness as anchors.

BACKGROUND: Morphine-sparing effects are often used to evaluate non-opioid analgesic interventions. The exact effect that would warrant the implementation of these interventions in clinical practice (a minimally important difference) remains unclear. We aimed to determine this with anchor-based methods. METHODS: This was a post hoc analysis of three studies investigating pain management after hip or knee arthroplasty (PANSAID [NCT02571361], DEX-2-TKA [NCT03506789] and Pain Map [NCT02340052]). The overall population was median aged 70, median ASA 2, 54% female. We examined the correlation between 0 and 24 h postoperative iv morphine equivalent consumption and the severity of nausea, vomiting, sedation and dizziness. The anchor was different severity degrees of these opioid-related adverse events. The primary outcome was the difference in morphine consumption between patients experiencing no versus only mild events. Secondary outcomes included the difference in morphine consumption between patients with mild versus moderate and moderate versus severe events. We used Hodges-Lehmann median differences, exact Wilcoxon-Mann-Whitney tests and quantile regression. RESULTS: The difference in iv morphine consumption was 6 mg (95% confidence interval: 4-8) between patients with no versus only mild events, 5 mg (2-8) between patients with mild versus moderate events and 0 mg (-4 to 4) between patients with moderate versus severe events. CONCLUSIONS: In populations comparable to this post-hoc analysis (orthopaedic surgery, median age 70 and ASA 2), we suggest a minimally important difference of 5 mg for 0-24 h postoperative iv morphine consumption.

Chronic dizziness in restless legs syndrome (RLS) patients responsive to levodopa or dopamine agonists.

Apart from the legs, restless legs syndrome (RLS) also affects the arms, head, neck, face, oral cavity, genital area, abdomen, intestines and bladder. RLS is also linked to several comorbid diseases, including headache disorders. Its association with dizziness has never been explored. We are reporting on two patients with RLS who also had a history of chronic dizziness. The treatment with levodopa or dopamine agonists completely alleviated both RLS and dizziness. We propose that RLS-like symptoms in the head may be experienced as dizziness and that dizziness may be part of the symptom complex of RLS. A large number of patients with chronic dizziness remain undiagnosed in clinical practice. We suggest exploring the history of RLS in patients presenting with chronic dizziness. Such patients may respond to levodopa or dopamine agonists. Because the response was seen in only two patients, a prospective placebo-controlled trial is needed to confirm these findings.

The safety of remimazolam versus propofol in gastroscopic sedation: a meta-analysis.

BACKGROUND: This meta-analysis was designed to compare the safety and efficiency of remimazolam with those of propofol in patients undergoing gastroscope sedation. METHODS: We searched PubMed, Cochrane Library, Embase, Ovid, Wanfang Database, China National Knowledge Infrastructure, SINOMED, and ClinicalTrials.gov for studies that reported on remimazolam versus propofol for gastroscope sedation from establishment to February 25, 2023. The sedative efficiency and the incidence of adverse events were assessed as outcomes. Version 2 of the Cochrane risk-of-bias assessment tool was used to assess the risk of bias. Review Manager 5.4 and STATA 17 were used to perform all statistical analyses. RESULTS: A total of 26 randomized controlled trials involving 3,641 patients were included in this meta-analysis. The results showed that remimazolam had a significantly lower incidence of respiratory depression (risk ratio [RR] = 0.40, 95% confidence interval [CI]: 0.28-0.57; p < 0.01, GRADE high), hypoxemia (RR = 0.34, 95% CI: 0.23-0.49; p < 0.01, GRADE high), bradycardia (RR = 0.34, 95% CI: 0.23-0.51; p < 0.01, GRADE high), dizziness (RR = 0.45, 95% CI: 0.31-0.65; p < 0.01, GRADE high), injection site pain (RR = 0.06, 95% CI: 0.03-0.13; p < 0.01, GRADE high), nausea or vomiting (RR = 0.79, 95% CI: 0.62-1.00; p = 0.05, GRADE moderate), and hypotension (RR = 0.36, 95% CI: 0.26-0.48; p < 0.01, GRADE low). CONCLUSIONS: Remimazolam can be used safely in gastroscopic sedation and reduces the incidence of respiratory depression, hypoxemia, bradycardia, injection site pain, and dizziness compared with propofol, and doesn't increase the incidence of nausea and vomiting.

Impact of antithrombotic therapy on acute and delayed intracranial haemorrhage and evaluation of the need of short-term hospitalisation based on CT findings after mild traumatic brain injury: experience from an oral and maxillofacial surgery unit.

PURPOSE: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings. METHODS: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis. RESULTS: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology-most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant. CONCLUSION: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation.

A Descriptive Analysis of Adverse Event Reports from the Quebec Cannabis Registry.

INTRODUCTION: Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation. METHODS: The Quebec Cannabis Registry (QCR) was a prospective registry of adults enrolled through participating physicians when they initiated MC between May 2015 and October 2018. Follow-up ended at MC discontinuation, loss to follow-up, three years, or end of data collection (May 2019). Data were collected at baseline and at follow-up visits every three months for the first two years, then once in the third year. Physicians filled adverse event (AE) reports, which were coded using MedDRA® preferred terms (PTs), and descriptive analyses were conducted. RESULTS: A total of 2991 patients were enrolled (mean age 50.9 years, 50.2% females). During follow-up, 108 patients (3.6%) experienced moderate or severe AEs, yielding 111 AE reports (three patients had two reports) and 214 AEs (average 1.9 AEs per report). Mild AEs were recorded as a reason for MC discontinuation for nine patients, but no AE reports were available. The most common PTs for ingested MC (62 reports) were dizziness (12.9%), nausea (11.3%), somnolence (9.7%), and vomiting (8.1%), and for inhaled MC (23 reports), headache (13.0%) was the most common. The most frequent PTs associated with tetrahydrocannabinol (THC)-dominant MC (25 reports) were dizziness and somnolence (12.0% each); for cannabidiol (CBD)-dominant MC (20 reports), vomiting (20.0%) was most common; and dizziness (17.2%), nausea (13.8%), somnolence (10.3%), and headache (8.6%) were the most frequent for balanced MC (58 reports). CONCLUSION: No new safety concerns were identified relative to the published literature, although notable differences in AE profile between modes of administration and cannabinoid content ratios should be considered by health professionals. Further work identifying and managing risk factors for AEs is warranted to maintain a favorable benefit-risk balance for MC.

Comparison of the effectiveness, safety, and costs of anti-Parkinson drugs: A multiple-center retrospective study.

AIMS: This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs). METHODS: This is a multi-center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs-related adverse events. RESULTS: A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56-355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088-0.135/day for levodopa/benserazide; $0.070-0.126/day for carbidopa/levodopa; $0.112-0.138/day for piribedil; $0.290-0.332/day for pramipexole; $0.229-0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031). CONCLUSIONS: Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.

Lamotrigine add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects. OBJECTIVES: To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 3 October 2022 with no language restrictions. CRS Web includes randomised and quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected trials and extracted data. Our primary outcome was 50% or greater reduction in seizure frequency. Our secondary outcomes were treatment withdrawal, adverse effects, cognitive effects, and quality of life. Primary analyses were by intention-to-treat. We performed sensitivity best- and worse-case analyses to account for missing outcome data. We calculated pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) for dichotomous outcomes. MAIN RESULTS: We identified no new studies for this update, so the results and conclusions of the review are unchanged. We included five parallel-group studies in adults or children, eight cross-over studies in adults or children, and one parallel study with a responder-enriched design in infants. In total, these 14 studies enroled 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks and treatment phases ranged from eight to 36 weeks. We rated 11 studies (1243 participants) at low overall risk of bias and three (697 participants) at unclear overall risk of bias due to lack of information on study design. Four studies (563 participants) reported effective blinding. Lamotrigine compared with placebo probably increases the likelihood of achieving 50% or greater reduction in seizure frequency (RR 1.80, 95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence). There is probably little or no difference in risk of treatment withdrawal for any reason among people treated with lamotrigine versus people treated with placebo (RR 1.11, 95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). Lamotrigine compared with placebo is probably associated with a greater risk of ataxia (RR 3.34, 99% Cl 2.01 to 5.55; 12 trials; 1525 participants; moderate-certainty evidence), dizziness (RR 1.76, 99% Cl 1.28 to 2.43; 13 trials; 1768 participants; moderate-certainty evidence), nausea (RR 1.81, 99% CI 1.22 to 2.68; 12 studies, 1486 participants; moderate-certainty evidence), and diplopia (RR 3.79, 99% Cl 2.15 to 6.68; 3 trials, 944 participants; moderate-certainty evidence). There is probably little or no difference in the risk of fatigue between lamotrigine and placebo (RR 0.82, 99% CI 0.55 to 1.22; 12 studies, 1552 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs.

Impact of Sex and Genetic Variation in Relevant Pharmacogenes on the Pharmacokinetics and Safety of Valsartan, Olmesartan and Hydrochlorothiazide.

Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide. Every volunteer was genotyped for 10 genetic variants in different transporters' genes. Additionally, valsartan-treated volunteers were genotyped for 29 genetic variants in genes encoding for different metabolizing enzymes. Variability in pharmacokinetic parameters such as maximum concentration (Cmax) and time to reach it (tmax), the incidence of adverse drug reactions (ADRs) and blood pressure measurements were analyzed as a function of pharmacogenetic and demographic parameters. Individuals with the ABCB1 rs1045642 T/T genotype were associated with a higher valsartan tmax compared to those with T/G and G/G genotypes (p < 0.001, ß = 0.821, R2 = 0.459) and with a tendency toward a higher postural dizziness incidence (11.8% vs. 0%, p = 0.070). A higher hydrochlorothiazide dose/weight (DW)-corrected area under the curve (AUC∞/DW) was observed in SLC22A1 rs34059508 G/A volunteers compared to G/G volunteers (p = 0.050, ß = 1047.35, R2 = 0.051), and a tendency toward a higher postural dizziness incidence (50% vs. 1.6%, p = 0.063). Sex impacted valsartan and hydrochlorothiazide pharmacokinetics, showing a lower exposure in women, whereas no significant differences were found for olmesartan pharmacokinetics.

Adverse Drug Reactions to Opioids: A Study in a National Pharmacovigilance Database.

INTRODUCTION: Opioids are commonly used as analgesics; however, like any medicine, they can produce adverse drug reactions (ADRs), including nausea, constipation, dependence, and respiratory depression, that result in harmful and fatal events. Therefore, it is essential to monitor the safety of these drugs in clinical practice. OBJECTIVE: This study aimed to characterize the safety profile of opioids by conducting a descriptive study based on a spontaneous reporting system (SRS) for ADRs in The Netherlands, focusing on abuse, misuse, medication errors, and differences between sexes. METHODS: Reports submitted to the Netherlands Pharmacovigilance Centre Lareb from January 2003 to December 2021 with an opioid drug as the suspected/interacting medicine were analyzed. Reporting odds ratios (RORs) for drug-ADR combinations were calculated, analyzed, and corrected for sex and drug utilization (expenditure) for the Dutch population. RESULTS: A total of 8769 reports were analyzed. Tramadol was the opioid with the most reports during the period (n = 2746), while oxycodone or tramadol had the highest number of reports per year in the study period. The most reported ADRs from opioid use were nausea, followed by dizziness and vomiting, independent of sex, and all of them were more often reported in women. Vomiting associated with tramadol (ROR females/males = 2.17) was significantly higher in women. Buprenorphine was responsible for most ADRs when corrected for expenditure, with high RORs observed with application site hypersensitivity, application site reaction, and application site rash. Fentanyl gave rise to most of the reports of ADRs concerning abuse, misuse, and medication errors. CONCLUSION: Patients treated with opioids experienced ADRs, primarily nausea, dizziness, and vomiting. For those groups of drugs, no significant differences were found between the sexes, except for the vomiting associated with tramadol. In general, ADRs related to opioids presented higher RORs when uncorrected and corrected for sexes and expenditure than other drugs. There was more disproportionate reporting for ADRs concerning abuse, misuse, and medication errors for opioids than other drugs in the Dutch SRS.

Amiodarone-Induced Nystagmus and Ataxia: Case Report and Systematic Review of Case Reports.

Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.

Perampanel and lacosamide monotherapy in pediatric patients with newly diagnosed focal epilepsy: A prospective study evaluating efficacy, tolerability, and behavior.

PURPOSE: Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy. METHODS: This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months. RESULTS: Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy. CONCLUSIONS: The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China.

Vertigo and Dizziness After Coronavirus Disease-2019 Vaccination: A Nationwide Analysis.

BACKGROUND: Side effects occurring after COVID-19 vaccination can include vertigo and dizziness. Despite its high incidence, few studies to date have assessed dizziness/vertigo after vaccination. The present study investigated the incidence of dizziness/vertigo after COVID-19 vaccination in South Korea. METHODS: Adverse reactions to COVID-19 vaccination reported to the Korea Disease Control and Prevention Agency from February 26, 2021, to July 31, 2022 (week 74) were analyzed. The incidence rates of dizziness/vertigo in subjects vaccinated with 5 COVID-19 vaccines, AZD1222 (AstraZeneca), BNT162b2 (Pfizer-BioNTech), JNJ-78436735 (Janssen), mRNA-1273 (Moderna), and NVX-CoV2373 (Novavax), were determined. RESULTS: A total of 126 725 952 doses of COVID-19 vaccine were administered, with 473 755 suspected adverse reactions (374 per 100 000 vaccinations) reported. Vertigo/dizziness was reported after the administration of 68 759 doses, or 54.3 per 100 000 vaccinations, making it the third most common adverse reaction after headache and muscle pain. CONCLUSION: Dizziness/vertigo was generally a mild adverse reaction after COVID-19 vaccination, but it was the third most common adverse reaction in Korea. Studies are necessary to clarify the causal relationship between vaccination and dizziness/vertigo and to prepare subjects for this possible adverse reaction.

Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy.

BACKGROUND: The safety and efficacy of low-sodium oxybate (LXB; Xywav®) were established in a randomized, double-blind, placebo-controlled, phase 3 withdrawal study in adults with narcolepsy with cataplexy; however, the longer-term safety profile has not yet been examined. The aim of the current analysis was to assess the time of onset and duration of common treatment-emergent adverse events (TEAEs) for LXB throughout the open-label optimized treatment and titration period (OLOTTP) and the stable dose period (SDP) portions of the main study, and the subsequent 24-week open-label extension (OLE). METHODS: In a double-blind, placebo-controlled, randomized withdrawal trial of LXB, TEAEs were evaluated during the 12-week OLOTTP, the 2-week SDP, and the subsequent 24-week OLE. Eligible participants were aged 18-70 years with a diagnosis of narcolepsy with cataplexy. At study entry, participants were taking sodium oxybate (SXB) alone, SXB with other anticataplectics, other anticataplectics alone, or were anticataplectic-treatment naive; other anticataplectics were tapered and discontinued during the OLOTTP. All participants initiated LXB during week 1 of the OLOTTP, and their dose was individually titrated based on safety and efficacy. Following the main study period, participants entered the OLE after rescreening (re-entry) after discontinuing LXB treatment or directly after completing the main study (rollover). TEAEs were assessed in the safety population as of database lock. TEAE duration was defined as time from TEAE start date to end date (or end of SDP or OLE, if end date was unrecorded). RESULTS: The safety population included 201 participants (SXB alone, n = 52; SXB with other anticataplectics, n = 23; other anticataplectics alone, n = 36; anticataplectic-treatment naive, n = 90). During the OLOTTP/SDP, headache was the most common LXB-emergent TEAE overall (71 events; n = 42 (21%); median (range) duration = 1 (1-147) day), followed by nausea (31 events; n = 26 (13%); median (range) duration = 9 (1-54) days) and dizziness (26 events; n = 21 (10%); median (range) duration = 7 (1-117) days). Among the 74 participants in the OLE, the most commonly reported TEAEs were headache (14 events; n = 7, 9%; peak incidence month 3 (n = 5/72); median (range) duration = 1 (1‒25) day), dizziness (8 events; n = 5, 7%; peak incidence month 1 (n = 3/74); median (range) duration = 26 (1‒181) days), and nasopharyngitis (6 events; n = 6, 8%; peak incidence month 6 (n = 2/69); median (range) duration = 9 (1‒24) days). Overall, study discontinuations attributed to TEAEs were 21/65 (32%) during the OLOTTP and SDP and 3/7 (43%) during the OLE. CONCLUSIONS: In this long-term analysis, the safety and tolerability profile of LXB was generally consistent with the known safety profile of SXB. During the OLOTTP and SDP, most TEAEs occurred early and were generally of short duration. TEAE prevalence decreased throughout the duration of the OLE; the most common TEAEs reported during the OLE were headache, dizziness, and nasopharyngitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03030599 (25 January 2017).

Low-sodium oxybate (LXB) is a medicine for narcolepsy. LXB treats daytime sleepiness and cataplexy (sudden muscle weakness). LXB is like sodium oxybate (SXB) but has 92% less sodium. This study looked at side effects in people taking LXB for many months. Three study periods were looked at in this report. In period 1, people could change their LXB dose for 12 weeks. This was to find their best dose. In period 2, people took that same best dose for 2 weeks. In period 3, some people kept taking LXB for 24 weeks. This was to study the longer-term effects. Everyone knew that they were taking LXB. During periods 1 and 2, the most common side effect was headache. Nausea and dizziness were also common. During period 3, headache was also the most common side effect. Dizziness and nasopharyngitis were also common. Nasopharyngitis is a cold in the nose and throat. In periods 1 and 2, most side effects happened early on. They also ended quickly. Fewer side effects happened in period 3. Among people leaving the study early, 32% left because of side effects during periods 1 and 2. During period 3, 43% left because of side effects. Overall, long-term side effects in people taking LXB were similar to those seen with SXB.

The safety of perampanel in different disorders and doses: A meta-analysis.

PURPOSE: To investigate the safety of perampanel in different disorders and doses. METHODS: Embase, the Cochrane Library, Medline, and ClinicalTrials.gov were searched from inception to July 2022 for randomized controlled trials (RCTs). The meta-analysis was performed by using Review Manager 5.3 and R 4.2.1 software. RESULTS: A total of 17 RCTs with 5711 subjects were included in the final analysis. The double-blind treatment phase was from 12 weeks to 48 weeks. Our results showed that 11 adverse events (aggression, ataxia, balance disorder, dizziness, fall, fatigue, irritability, rash, somnolence, vertigo, and weight increase) were statistically significantly associated with perampanel, and 4 of them (ataxia, dizziness, fatigue, and somnolence) showed a clear dose-response relationship. Psychiatric adverse events occurred most frequently among serious treatment-emergent adverse events (TEAEs). At 8 mg/day, seven adverse events (aggression, balance disorder, dizziness, fatigue, irritability, vertigo, and weight increase) occurred more frequently in patients with epilepsy than in patients with other disorders, whereas dose discontinuation rates due to adverse events were lower in patients with epilepsy than in patients with other disorders. CONCLUSION: The safety profile of perampanel is dependent on diseases and dose. The risk of adverse events was statistically significantly higher, with doses exceeding 4 mg/day. Despite a higher risk of adverse events, patients with epilepsy had a lower perampanel discontinuation rate than patients with other disorders.

Use of Remimazolam Combined With Alfentanil for Plastic Surgery Anesthesia Cases: A Clinical Trial.

OBJECTIVE: This study aims to observe the safety and effectiveness of remimazolam benzenesulfonate combined with alfentanil for painless and comfort anesthesia in plastic surgery. METHODS: Two hundred patients with American Society of Anesthesiologists (ASA) I-II for elective facial autologous lipofilling + autologous liposuction (thigh or abdomen) plastic surgery in our hospital were selected. One hundred patients received comfort anesthesia (observation group) on odd-numbered day of surgery, and other 100 patients received painless anesthesia (control group) on even-numbered day. Patients in both groups were given slow injection of remimazolam benzenesulfonate 0.1 mg/kg and alfentanil 5 µg/kg to induce sleep before local anesthesia. Depending on body action reaction to surgical stimulation, patients in the observation group were received with remimazolam 0.05 mg/kg and alfentanil 2.5 µg/kg for maintenance until the end of surgery after local anesthesia, and patients in the control group received with remimazolam 0.25 to 0.5 mg/kg/h and alfentanil 25 to 50 µg/kg/h in continuous pumps. Time to fall asleep, sedation score, time to end of medication, time to open eyes, recovery score, and the presence of body movement, glossoptosis, arousal or jaw support during hypoxia, hypotension, bradycardia, operation time, total amount of remimazolam and alfentanil used, and the presence of postoperative complications such as pruritus, dizziness, nausea, and vomiting were recorded in both 2 groups. RESULTS: There were no significant differences in the preoperative vital sign parameters as mean arterial pressure, heart rate, and oxygen saturation between 2 groups ( P > 0.05). Intraoperative mean arterial pressure and heart rate were significantly lower in both groups compared with preoperative ( P < 0.05), but there was no statistically significant between the 2 groups ( P > 0.05). There was no significant decrease in oxygen saturation in both groups under the condition of intraoperative oxygen inhalation ( P > 0.05). There was no significant difference between the 2 groups in the incidence of adverse reactions, such as intraoperative body movement induced by skin cutting, glossoptosis requiring jaw thrust, postoperative pruritus, dizziness, nausea, and vomiting ( P > 0.05). There was no statistically significant difference in time to fall asleep, sedation score during local anesthesia, time to open eyes after stopping anesthetics, and recovery score between the 2 groups ( P > 0.05). Meanwhile, the total amount of remimazolam and alfentanil use was significantly reduced in patients in the observation group compared with the control group ( P < 0.05). CONCLUSIONS: Remimazolam benzenesulfonate combined with alfentanil can be used as a comfort anesthesia and painless anesthesia protocol in plastic surgery, which has the advantages of rapid onset of action, safety and comfort for patients, rapid recovery, and good cooperation. Furthermore, the protocol of remimazolam benzenesulfonate combined with alfentanil used in the observation group can significantly reduce the total amount of remimazolam and alfentanil used.

Prevention of Pregabalin-Related Side Effects Using Slow Dose Escalation Before Surgery: A Trial in Primary Total Joint Arthroplasty Within the Enhanced Recovery After Surgery Pathway.

BACKGROUND: The side effects of pregabalin likely occur after the first dose. We aimed to evaluate the effect of 75 milligrams (mg) of pregabalin prescribed as an initial dose with a slow dose escalation for primary total joint arthroplasty within the enhanced recovery after surgery pathway. METHODS: Participants were randomly assigned to two groups. Fifty-eight patients were enrolled, and twenty-nine were assigned to each group. Group 1 (G1) received pregabalin (37.5 mg) twice on the day before surgery, as well as pregabalin 75 mg two hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose of pregabalin at two hours pre-operatively. The primary outcome was dizziness assessed by severity; secondary outcomes included nausea, vomiting, sedation, opioid consumption, independent transfer at six hours post-operatively, time to readiness for independent transfers, time to readiness for discharge, and pain. RESULTS: At two, four, and six hours post-operatively, the proportion of patients experiencing dizziness and nausea was significantly greater in G2 than in G1, and opioid consumption was significantly greater in G2 than in G1 (P = .012). The proportion of independent transfers at six hours post-operatively was significantly greater in G1 than in G2 (P = .010). The time to readiness for independent transfers was significantly shorter in G1 than in G2 (P = .016). CONCLUSION: Prescription of pregabalin 37.5 mg twice on the day before surgery was effective in reducing early postoperative dizziness and nausea after receiving pregabalin 75 mg two hours pre-operatively. It also promoted early independent transfers and reduced opioid consumption.

Comparison of remimazolam and propofol about safety outcome indicators during general anesthesia in surgical patients: a systematic review and meta-analysis.

INTRODUCTION: Remimazolam is a novel sedative drug that has been successively approved for procedural sedation and general anesthesia, however, which has not been fully explored due to limited clinical studies and a small sample size. Current clinical studies have focused on the use of remimazolam and propofol for general anesthesia (GA) as indicators of safety outcomes in surgical patients, but different studies have reached different conclusions. The aim of this study was to investigate whether the safety-related outcome indicators in GA were superior to propofol in surgical patients. EVIDENCE ACQUISITION: We systematically searched PubMed, Cochrane Library, Embase, and Web of Science databases for all published randomized controlled trials comparing remimazolam with propofol for general anesthesia. Data from eligible studies were pooled with relative risk or mean differences to analyze the differences in hemodynamic stability and adverse effects of the two medications. EVIDENCE SYNTHESIS: Eight randomized controlled trials involving 998 participants were included. Compared with propofol, remimazolam had better hemodynamic stability with a lower incidence of hypotension (RR=0.43, 95% CI: [0.34, 0.55], I2=0%, P<0.00001), a higher preintubation, and immediate postintubation mean arterial pressure (MAP, MD=5.41, 95% CI: [5.26,11.24], Z=5.41, P<0.00001<0.05); (MD=1.60, 95% CI: [-0.20, 3.41], Z=1.74, P<0.08>0.05). Regarding other adverse events, the incidence of hypoxemia, nausea and vomiting, dizziness and injection site pain was lower in the remimazolam group compared to the propofol group. CONCLUSIONS: In this Meta-analysis, compared with propofol, remimazolam for GA reduced the incidence of hypotension, hypoxemia, nausea and vomiting, dizziness and injection site pain, and had a more stable MAP before and after intubation, which supported that remimazolam is a safer sedative. However, a large sample is needed to validate this finding.