Amifampridines are the Most Effective Drugs for Treating Lambert-Eaton Myasthenic Syndrome With a Focus on Pediatric Lambert-Eaton Myasthenic Syndrome.

In 1983, the first successful trial of 3,4-diaminopyridine (3,4-DAP) in Lambert-Eaton myasthenic syndrome (LEMS) was reported. Efficacy of amifampridine (3,4-DAP and 3,4-diaminopyridine phosphate [3,4-DAPP]) for symptomatic treatment in LEMS was proven by seven randomized studies in 3,4-DAP and two randomized studies in 3,4-DAPP. US Food Drug Administration approved 3,4-DAPP usage for adult LEMS in 2018 and for pediatric LEMS in 2022. Nineteen pediatric LEMS cases were identified in the literature. Compared with adult LEMS, the rate of malignancy is low as expected and the rate of dysautonomia is also low in pediatric LEMS. Unexpected finding is two cases of pediatric LEMS following antecedent infection. Amifampridine can be safely used as long the daily dose is less than 80 mg a day for adult LEMS patients and less than 30 mg a day for pediatric LEMS patients. Amifampridines can be supplemented with a liberal amount of pyridostigmine for long term usage. Amifampridine was used as symptomatic treatment in eight (42%) of 19 pediatric LEMS patients: 3,4-DAP in six and 3,4-DAPP in two patients. The most common practice of 3,4-DAP was a combination with pyridostigmine in four patients. With 3,4-DAP, normal activity was reported in 3 cases and mild to moderate-improvement in other 3 cases. In two patients with 3,4-DAPP, significant improvement in one and no improvement in one. Amifampridines are proven to be effective and safe drugs for the symptomatic treatment without serious side reaction in adults as well as in children as long as the dosage is properly adhered.

Symptomatic and Preventive Medication Use before and after Alzheimer's Disease Diagnosis: A 10-Year Matched Cohort Study.

OBJECTIVE: To investigate longitudinal changes in symptomatic and preventive medication use among community-dwelling people with and without Alzheimer's disease (AD) 5 years pre- and post-AD diagnosis. DESIGN: Retrospective matched cohort study. SETTINGS AND PARTICIPANTS: The sample comprised 58,496 people with a geriatrician/neurologist-verified AD diagnosis matched 1:1 for age, sex, and region to people without AD in Finland. METHODS: Medication dispensing data were obtained from the Finnish Prescription Register. Prevalence of symptomatic and preventive medication use was evaluated every 6 months from 5 years pre- to post-AD diagnosis. Longitudinal changes in medication use between people with and without AD were compared using ordinal logistic regression. RESULTS: During the 5 years pre- and post-diagnosis, there were differences in symptomatic (P < .001) and preventive (P = .006) medication use between people with and without AD. Over the 5 years pre-diagnosis, prevalence of symptomatic and preventive medications increased in both people with and without AD. During the 1 year pre-diagnosis, people with AD had a higher increase in use of ≥3 symptomatic medications (+4.4% vs +2.2%) and ≥3 preventive medications (+6.4% vs +2.9%) compared to people without AD. Over the 5 years post-diagnosis, symptomatic medication use plateaued in both people with and without AD. Meanwhile, people using ≥3 preventive medications decreased (-6.0%) in those with AD, but increased (+6.1%) in those without AD. During the follow-up period, people with AD had a larger absolute percentage increase in prevalence of antipsychotics (+22.7% vs +1.8%) and antidepressants (+19.1% vs +5.0%) than people without AD. During the same period, paracetamol and calcium supplement use increased by 31.1% and 20.4%, respectively, among people with AD. The largest absolute percentage decrease in prevalence of preventive medications over the 5 years post-diagnosis were beta-blockers (-9.8%) and statins (-7.0%) in people with AD. CONCLUSIONS AND IMPLICATIONS: At the point of and following diagnosis, there were population-level changes in medication use among people with AD. Medication assessments during this period appear to coincide with discontinuation of preventive medications whereas minimal changes were observed in symptomatic medication use.

A mixed-methods study on the pharmacological management of pain in Australian and Japanese nursing homes.

BACKGROUND: Understanding how analgesics are used in different countries can inform initiatives to improve the pharmacological management of pain in nursing homes. AIMS: To compare patterns of analgesic use among Australian and Japanese nursing home residents; and explore Australian and Japanese healthcare professionals' perspectives on analgesic use. METHODS: Part one involved a cross-sectional comparison among residents from 12 nursing homes in South Australia (N = 550) in 2019 and four nursing homes in Tokyo (N = 333) in 2020. Part two involved three focus groups with Australian and Japanese healthcare professionals (N = 16) in 2023. Qualitative data were deductively content analysed using the World Health Organization six-step Guide to Good Prescribing. RESULTS: Australian and Japanese residents were similar in age (median: 89 vs 87) and sex (female: 73% vs 73%). Overall, 74% of Australian and 11% of Japanese residents used regular oral acetaminophen, non-steroidal anti-inflammatory drugs or opioids. Australian and Japanese healthcare professionals described individualising pain management and the first-line use of acetaminophen. Australian participants described their therapeutic goal was to alleviate pain and reported analgesics were often prescribed on a regular basis. Japanese participants described their therapeutic goal was to minimise impacts of pain on daily activities and reported analgesics were often prescribed for short-term durations, corresponding to episodes of pain. Japanese participants described regulations that limit opioid use for non-cancer pain in nursing homes. CONCLUSION: Analgesic use is more prevalent in Australian than Japanese nursing homes. Differences in therapeutic goals, culture, analgesic regulations and treatment durations may contribute to this apparent difference.

Deprescribing Opportunities for Frail Residents of Nursing Homes: A Multicenter Study in Australia, China, Japan, and Spain.

OBJECTIVE: Deprescribing opportunities may differ across health care systems, nursing home settings, and prescribing cultures. The objective of this study was to compare the prevalence of STOPPFrail medications according to frailty status among residents of nursing homes in Australia, China, Japan, and Spain. DESIGN: Secondary cross-sectional analyses of data from 4 cohort studies. SETTING AND PARTICIPANTS: A total of 1142 residents in 31 nursing homes. METHODS: Medication data were extracted from resident records. Frailty was assessed using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Chi-square tests and prevalence ratios (PRs) were used to compare STOPPFrail medication use across cohorts. RESULTS: In total, 84.7% of non-frail, 95.6% of frail, and 90.6% of most-frail residents received ≥1 STOPPFrail medication. Overall, the most prevalent STOPPFrail medications were antihypertensives (53.0% in China to 73.3% in Australia, P < .001), vitamin D (nil in China to 52.7% in Australia, P < .001), lipid-lowering therapies (11.1% in Japan to 38.9% in Australia, P < .001), aspirin (13.5% in Japan to 26.2% in China, P < .001), proton pump inhibitors (2.1% in Japan to 32.0% in Australia, P < .001), and antidiabetic medications (12.3% in Japan to 23.5% in China, P = .010). Overall use of antihypertensives (PR, 1.15; 95% CI, 1.06-1.25), lipid-lowering therapies (PR, 1.78; 95% CI, 1.45-2.18), aspirin (PR, 1.31; 95% CI, 1.04-1.64), and antidiabetic medications (PR, 1.31; 95% CI, 1.00-1.72) were more prevalent among non-frail and frail residents compared with most-frail residents. Antihypertensive use was more prevalent with increasing frailty in China and Japan, but less prevalent with increasing frailty in Australia. Antidiabetic medication use was less prevalent with increasing frailty in China and Spain but was consistent across frailty groups in Australia and Japan. CONCLUSIONS AND IMPLICATIONS: There were overall and frailty-specific variations in prevalence of different STOPPFrail medications across cohorts. This may reflect differences in prescribing cultures, application of clinical practice guidelines in the nursing home setting, and clinician or resident attitudes toward deprescribing.

Sensory Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Neglected Immunotherapy-Responsive Sensory Neuropathy.

BACKGROUND AND PURPOSE: To report an improvement with immunotherapy in 34 (85%)/40 patients who required an immunotherapy among 56 patients with sensory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired, chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy that had progressed for >2 months; and 2) definite electrophysiological and/or biopsy evidence of demyelinating neuropathy. RESULTS: Fifty-six patients with sensory CIDP were identified. Evidence of demyelination was obtained from by the routine motor nerve conduction study (NCS) in 39 (70%) patients, from a nerve biopsy in 10, and from a near-nerve needle sensory NCS in 7 patients. The most prominent laboratory abnormality was a high protein level in the cerebrospinal fluid in 21 (49%) of 43 tested patients. Immunotherapy was required in 41 (79%) of the 52 followed-up patients. An improvement with immunotherapy was observed in 36 (88%)/41 patients. In three patients, motor weakness developed in 5-8 years' follow-up period and so, their diagnosis was changed to CIDP. CONCLUSIONS: Sensory CIDP is responded to an immunotherapy in 88% of the treated patients. Sensory CIDP was diagnosed by the routine motor NCS in 70% of patients and by a sural nerve biopsy in 18% of patients. Thus, sensory CIDP should be recognized as a treatable CIDP variant among the different types of "idiopathic sensory neuropathy."

Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes.

OBJECTIVE: To investigate symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes (NHs). METHODS: Secondary cross-sectional analyses of two prospective cohort studies involving 12 Australian NHs and four Japanese NHs. Frailty was measured using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Regular medications were classified as symptomatic or preventive based on published lists and expert consensus. Descriptive statistics were used to compare the prevalence and ratio of symptomatic to preventive medications. RESULTS: Overall, 550 Australian residents (87.7 ± 7.3 years; 73.3% females) and 333 Japanese residents (86.5 ± 7.0 years; 73.3% females) were included. Australian residents used a higher mean number of medications than Japanese residents (9.8 ± 4.0 vs 7.7 ± 3.7, p < 0.0001). Australian residents used more preventive than symptomatic medications (5.5 ± 2.5 vs 4.3 ± 2.6, p < 0.0001), while Japanese residents used more symptomatic than preventive medications (4.7 ± 2.6 vs 3.0 ± 2.2, p < 0.0001). In Australia, symptomatic medications were more prevalent with increasing frailty (non-frail 3.4 ± 2.6; frail 4.0 ± 2.6; most-frail 4.8 ± 2.6, p < 0.0001) but less prevalent with age (< 80 years 5.0 ± 2.9; 80-89 years 4.4 ± 2.6; ≥ 90 years 3.9 ± 2.5, p = 0.0042); while preventive medications remained similar across age and frailty groups. In Japan, there was no significant difference in the mean number of symptomatic and preventive medications irrespective of age and frailty. CONCLUSIONS: The ratio of symptomatic to preventive medications was higher with increasing frailty but lower with age in Australia; whereas in Japan, the ratio remained consistent across age and frailty groups. Preventive medications remained prevalent in most-frail residents in both cohorts, albeit at lower levels in Japan.

National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

Experiences of hospitalized smokers initiated on varenicline as part of a pragmatic smoking cessation trial.

Varenicline is an effective monotherapy for smoking cessation, but adherence is often suboptimal. This qualitative study explored the experiences of varenicline treatment among participants enrolled in a randomized controlled trial, who self-reported being adherent or nonadherent to varenicline treatment (n = 15). Individual interviews were conducted using a semi-structured interview guide. Data were analyzed using thematic framework approach. An environment of forced abstinence played a key role in motivating quit attempts. The main barriers to varenicline adherence were medicine-related side effects, relapse to smoking, and a belief that the medication was not working if abstinence was not achieved by the target quit date. Participants adherent to treatment adopted a reduce-to-quit approach and noticed a gradual reduction in cigarette cravings. When asked about their preferences for support while on varenicline treatment, participants expressed the need for proactive follow-up by health professionals and more active behavioral support to assist them in adhering to treatment. Prescribers should encourage varenicline users to persist with treatment, even if abstinence is not achieved by the target quit date. Further research is needed to explore the awareness and acceptability of the reduce-to-quit method among prescribers and patients and its impact on varenicline adherence and in term long-term abstinence.

Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B.

Introduction: Club cells are precursors for mucus-producing goblet cells. Interleukin 1ß (IL-1B) is an inflammatory mediator with pro-mucin activities that increases the number of mucus-producing goblet cells. IL-1B-mediated mucin production in alveolar adenocarcinoma cells requires activation of the cAMP response element-binding protein (CREB). Whether the pro-mucin activities of IL-1B require club cell CREB is unknown. Methods: We challenged male mice with conditional loss of club cell Creb1 and wild type littermates with intra-airway IL-1B or vehicle. Secondarily, we studied human "club cell-like" H322 cells. Results: IL-1B increased whole lung mRNA of secreted (Mucin 5ac, Mucin 5b) and tethered (Mucin 1, Mucin 4) mucins independent of genotype. However, loss of club cell Creb1 increased whole lung mRNA of member RAS oncogene family (Rab3D), decreased mRNA of the muscarinic receptor 3 (M3R) and prevented IL-1B mediated increases in purinergic receptor P2Y, (P2ry2) mRNA. IL-1B increased the density of goblet cells containing neutral mucins in wildtype mice but not in mice with loss of club cell Creb1. These findings suggested that club cell Creb1 regulated mucin secretion. Loss of club cell Creb1 also prevented IL-1B-mediated impairments in airway mechanics. Four days of pharmacologic CREB inhibition in H322 cells increased mRNA abundance of forkhead box A2 (FOXA2), a repressor of goblet cell expansion, and decreased mRNA expression of SAM pointed domain containing ETS transcription factor (SPDEF), a driver of goblet cell expansion. Chromatin immunoprecipitation demonstrated that CREB directly bound to the promoter region of FOXA2, but not to the promoter region of SPDEF. Treatment of H322 cells with IL-1B increased cAMP levels, providing a direct link between IL-1B and CREB signaling. Conclusion: Our findings suggest that club cell Creb1 regulates the pro-mucin properties of IL-1B through pathways likely involving FOXA2.

High-Resolution T2-Weighted Imaging for Surveillance in Postoperative Vestibular Schwannoma: Equivalence with Contrast-Enhanced T1WI for Measurement and Surveillance of Residual Tumor.

BACKGROUND AND PURPOSE: Patients with surgically resected vestibular schwannoma will undergo multiple postoperative surveillance examinations, typically including postcontrast sequences. The purpose of this study was to compare high-resolution T2WI with gadolinium T1WI in the postoperative assessment of vestibular schwannoma. MATERIALS AND METHODS: This was a retrospective study of patients with a history of resected vestibular schwannoma at a single institution. High-resolution T2WI and gadolinium T1WI were independently evaluated for residual disease. In addition, 3D and 2D measurements were performed in the group of patients with residual tumor. Statistical analysis was performed to evaluate the agreement between sequences on the binary assessment (presence/absence of tumor on initial postoperative examination) and to evaluate the equivalence of measurements for the 2 sequences on 3D and 2D quantitative assessment in individuals with residual disease. RESULTS: One hundred forty-eight patients with retrosigmoid-approach resection of vestibular schwannomas were included in the final analysis. There was moderate-to-substantial agreement between the 2 sequences for the evaluation of the presence versus absence of tumor (Cohen κ coefficient = 0.78; 95% CI, 0.68-0.88). The 2 sequences were significantly equivalent for 2D and 3D quantitative assessments (short-axis P value = .021; long-axis P value = .015; 3D P value = .039). CONCLUSIONS: In this retrospective study, we demonstrate moderate-to-substantial agreement in the categoric assessment for the presence versus absence of tumor and equivalence between the 2 sequences for both 2D and volumetric tumor measurements as performed in the subset of patients with measurable residual. On the basis of these results, high-resolution T2WI alone may be sufficient for early postoperative imaging surveillance in this patient population.

Life-Long Steroid Responsive Familial Myopathy With Docking Protein 7 Mutation.

ABSTRACT: Docking protein 7 (DOK7) congenital myasthenic syndrome (CMS) is characterized by limb-girdle weakness and lack of fluctuating fatigability simulating many familial myopathies. Albuterol is the first line of therapy in view of consistent improvement. Two brothers with progressive predominant biceps weakness for 1-3 years responded to prednisone treatment for 40-50 years. Various studies including muscle biopsy and many laboratory studies were unsuccessful for the definite diagnosis. Gene study, 40 years after the initial evaluation, confirmed the diagnosis of DOK7 CMS. These are the first reported cases of DOK7 CMS associated with a sustained benefit from corticosteroids.

Primary repair of extensor pollicis longus rupture after volar locking plating for distal radial fracture.

We presumed that primary repair would be possible if the extensor pollicis longus (EPL) rupture after volar locking plating (VLP) for distal radius fracture (DRF) was diagnosed earlier. Thus, five cases of EPL ruptures were resolved via primary repair rather than extensor indicis proprius (EIP) transfer, so we reported the clinical outcomes of at least 2 years follow-up since EPL repair. Of 588 consecutive patients with the fractures treated between January 2016 and December 2019, 501 who met out inclusion/exclusion criteria were initially investigated. We informed patients of: (1) the ordinary range of motion of thumb at full wrist flexion/extension; (2) the proper tone of thumb extension compared to the contralateral thumb; and (3) the degree of pain/discomfort during thumb exercise. After discharge, we called each patient monthly commencing at 8 weeks postoperatively to enquire if any of those had worsened, by telephone. Five patients had ruptured EPLs diagnosed at a mean of postoperative-12.8 weeks. Three came to outpatient department for suspected tendon rupture just after telephone survey with the authors. The other two visited after detecting insufficiency in the three items, during the period between telephone inquiries. In four, the torn EPL were encapsulated by tendon sheathes. Extension lag at interphalangeal joint was absent and other clinical outcomes associated with DRF were all satisfactory at final follow-up. Primary repair of EPL rupture (rather than EIP transfer) is possible if patients are properly followed up after VLP for DRF. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Continuing perioperative estrogen therapy does not increase venous thromboembolic events in transgender patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). MATERIALS AND METHODS: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. RESULTS: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). CONCLUSIONS: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.

Association between non-vascularised bone graft failure and compartment of the defect in mandibular reconstruction: a systematic review and meta-analysis.

Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.

Neuromuscular junction disorders beyond myasthenia gravis.

PURPOSE OF REVIEW: To give an overview of the recent data on three autoimmune neuromuscular junction disorders with the recent Food Drug Administration (FDA) approval of amifampridine [3,4-Diaminopyridine (3,4-DAP) and 3,4-diaminopyridine phosphate (3,4-DAPP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). RECENT FINDINGS: In LEMS, the most important recent development is the introduction of FDA approved amifampridine for the symptomatic treatment. Randomized controlled studies showed an extremely effective improvement with amifampridine with daily dose of ≤ 80 mg with minimal side reactions. The next important development is in the electrodiagnostic criteria. Now 10 s exercise and an incremental response ≥ 60% either after 10 s exercise or at the high-rate stimulation in the repetitive nerve stimulation test are recommended as the standard tests.In 2016, myasthenia-gravis Lambert-Eaton overlap syndrome (MLOS) was coined as new syndrome for patients with myasthenia gravis and LEMS combined symptoms in same patients.In Isaacs syndrome, voltage gated calcium channel antibody order is no longer recommended because of low specificity for immunotherapy responsive disorders. Instead, ' leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated like-2 (CASPR2) autoantibody tests' are recommended. SUMMARY: In LEMS, amifampridine (3,4 DAP and 3,4-DAPP) is approved by the FDA as an effective symptomatic treatment. MLOS is coined as new syndrome recently. In Isaacs syndrome, LGI1 and CASPR2 antibody tests are recommended.

Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports.

OBJECTIVE: Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use. MATERIALS AND METHODS: We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC). RESULTS: A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected; the IC025 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%], ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]). CONCLUSIONS: Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting.

Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer: systematic review and meta-analysis.

OBJECTIVE: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC. MATERIALS AND METHODS: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study. RESULTS: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001). CONCLUSIONS: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.

Development and Validation of a Multidimensional Frailty Scale for Clinical Geriatric Assessment.

OBJECTIVES: This study aims to develop a multidimensional frailty assessment tool including physical, psychological, and social frailty and to examine its psychometric property in a clinical setting. METHODS: Through a literature review and gathered expert perspectives, the Korean Frailty Scale (KFS, 0-6 points) was developed with six questions about weight loss, self-assessment of health status, energy loss, fatigue, social network, and support. The psychometric property was then validated in community-dwelling older adults using the Korean Frailty and Aging Cohort Survey (2016-2019). Receiver operator characteristic (ROC) analyses determined optimal cutoff scores for frail, pre-frail, and robust. The predictive validity for mortality, hospitalization, fall events, and disability, such as declines in activities of daily living (ADL) and instrumental activities of daily living (IADL) was assessed after adjusting for age, sex, education level, household income, body-mass index, smoking status, alcohol consumption, physical activity, marital status, current employment, and residence. RESULTS: The 2,923 participants (mean age: 76.0±3.9 years, female: 52.2%) were categorized into frail (≥3 points, 21.1%), pre-frail (1-2 points, 50.2%) and robust (0 points, 28.7%) groups. Sensitivity (88.3%), specificity (91.6%), and the area under the ROC curve (0.730) for the frail group were sufficient to be accepted as a new frailty scale. The frail group had increased risk of falling (relative risk [RR]: 1.810, 95% confidence interval: 1.354-2.420), mortality (hazard ratio, 6.596, 1.802-24.137), and IADL decline (RR, 1.638, 1.231-2.178). CONCLUSION: The KFS is a new multidimensional frailty scale for clinical geriatric assessment that was confirmed as effective for predicting adverse health outcomes in Korean community-dwelling older adults.