Postintervention Status Research Articles

Eculizumab for Acetylcholine Receptor-positive Generalized Myasthenia Gravis: Single Center Experience (P7-8.009)

<h3>Objective:</h3> To describe the baseline characteristics, treatment and safety outcomes of the patients with acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) treated with eculizumab in our clinic. <h3>Background:</h3> Safety and outcomes data on eculizumab for AChR+ gMG in real world clinical practice remain limited. <h3>Design/Methods:</h3> Patients with refractory AChR+ gMG who received &gt; 6 dose of eculizumab at the Department of Neurology, Istanbul Faculty of Medicine were included in the study. After consent, demographic data, MG Foundation of America (MGFA) classification before eculizumab initiation, MG activities of daily living (MG-ADL) scores, MGFA post intervention status (MGFA-PIS) before and after eculizumab and serious adverse events (SAEs) during the treatment were collected from medical records, retrospectively. <h3>Results:</h3> Ten patients were included in the study, six of them were female. Mean age at eculizumab initiation was 44.3 years (range, 29–71). Four had history of thymoma and all patients had thymectomy. Mean follow-up duration after eculizumab was 6 months (range, 2–12 months). After six months of eculizumab treatment, all patients achieved improved status (7/7) and five of patients (5/7) had minimal manifestation status. Mean MG-ADL decreased from 9 to 1.2 at 1 month. All of our patients discontinued maintenance IVIG. No meningococcal infections were reported. Two patients had Covid-19 infection with favorable outcome during eculizumab treatment. One patient had mild arthralgia and two other had upper respiratory tract infection during treatment. <h3>Conclusions:</h3> Our data provide additional evidence of the safety and effectiveness of eculizumab for refractory gMG treatment in real-world clinical practice. <b>Disclosure:</b> Dr. Durmus has nothing to disclose. Arman Cakar has nothing to disclose. Dr. Parman has nothing to disclose.

Comorbid Contributors to Fatigue in Myasthenia Gravis (P7-8.010)

<h3>Objective:</h3> To characterize fatigue in patients with myasthenia gravis, identify other comorbid factors that contribute to it and propose routine screening recommendations. <h3>Background:</h3> Fatigue is a frequent complaint in patients with myasthenia gravis. However, it is non-specific and often associated with other medical conditions. Some of the most frequent causes of fatigue can be indirectly related to myasthenia and its treatment or another simultaneous condition. With this study, the goal is to guide providers on weather to routinely screen for comorbid, potentially treatable causes of fatigue in MG patients. <h3>Design/Methods:</h3> Patients were recruited from VCU Neurology clinics. Inclusion criteria were adults with a confirmed diagnosis of myasthenia gravis from positive antibodies or electrodiagnostic testing. Enrolled patients had a battery of serum laboratory tests collected that included B12, MMA, CBC, TSH and testosterone levels in men. They also filled out questionnaires including PSQI, Epworth Sleepiness Scale and Neurology QoL surveys for fatigue, depression and anxiety. Patients and their primary neurologists were notified of any abnormal lab results and their participation in the study did not have any influence on management of their disease. <h3>Results:</h3> 28 patients were enrolled in this study, completed the questionnaires and had laboratory studies collected. 19 patients were female and 9 were male. 68% of patients had an MGFA post-intervention status of MM3. 61% of patients had a fatigue severity scale &gt;36 and 68% scored &gt;50 on the fatigue portion on the QOL questionnaire. 43% of patients had abnormal laboratory results, mostly either anemia or vitamin D deficiency. Regarding sleep, 75% had a PSQI score &gt;5. For psychiatric comorbidities, 46% scored &gt;50 on the anxiety and 50% scored &gt;50 on the depression portion. <h3>Conclusions:</h3> The results of this study suggest that fatigue in patients with myasthenia gravis is multifactorial and routine screening for other causes is warranted. <b>Disclosure:</b> Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Strongbridge. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Gwathmey has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Patel has nothing to disclose. Ms. Parolisi has nothing to disclose.

Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials.

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

Effect of Thymectomy on Outcomes of Myasthenia Gravis Patients: A Case-Control Study at a Tertiary Care Hospital.

Background and objective Myasthenia gravis (MG) is an acquired autoimmune disease mediated by antibodies affecting the neuro-muscular junction on the postsynaptic membrane, resulting in neuromuscular transmission obstruction and, consequently, muscle weakening. It is believed that the thymus gland plays a critical role in the production of these antibodies. Screening patients for thymoma and surgical excision of the thymus gland is a crucial part of the treatment. To compare the odds of good outcomes in Myasthenia Gravis patients with or without thymectomy. Material and methods A retrospective case-control study was conducted at the Department of Medicine and Neurology, Ayub Teaching Hospital, Abbottabad, Pakistan, from October 2020 to September 2021. A purposive sampling technique was employed. Thirty-two MG patients with thymectomy and 64 MG patients without thymectomy were selected for investigation. Controls and cases were matched on the basis of sex and age (1:2). A positive EMGstudy, acetylcholine receptor antibodies, and a pyridostigmine testwere used to make the diagnosis of MG. Patients were called to the outpatient department for assessment of treatment outcomes. Primary outcome evaluation was done using the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) tool at the last follow-up after one year. Results A sample of 96 patients was evaluated, of which 63 (65%) were females and 33 (34%) were males. The mean age for Group 1 (cases) was 35 years ±8.9 and for Group 2 (controls) was 37± 11.1. Age and Osserman stages were shown to be the two most crucial prognostic factors in our study. However, there are several other factors in our study that are linked to a poor response, such as a greater BMI, dysphagia, thymoma, older age, and a longer duration of disease. Conclusions Our findings indicate that none of the analysed groups had significantly worse outcomes as a result of the current clinical practice of thymectomy patient selection.

Effects of comorbid diseases on clinical outcomes in patients with myasthenia gravis.

This cross-sectional study was undertaken to evaluate the existence and distribution of comorbid disorders among myasthenia gravis (MG) patients according to subgroups and to identify the effects of the comorbid diseases of MG patients on clinical outcomes. The patients were divided into six subgroups according to serum antibodies, age at onset, and thymoma presence. All patients were treated in line with the International Consensus Guidance for Management of Myasthenia Gravis. To assess the clinical outcome after treatment for MG, we used the MGFA Post-intervention Status. In generalized MG patients, the good prognosis group included patients who were classified as having minimal-manifestation status or better. In ocular MG patients, the remission subgroup included patients who were classified as having complete stable remission or pharmacological remission status. Our study included 168 MG patients, 85 were female while 83 were male. Comorbid diseases were present in 124 (73.8%) MG cases. After at least 1year of follow-up, 106 (86.8%) of the generalized MG patients were in the good prognosis group and 16 (13.2%) generalized MG patients were in the poor prognosis group. 27 (58.6%) ocular MG patients were in the remission group and 19 (41.3%) ocular MG patients were in the non-remission group. Hypertension increased the risk of poor prognosis by 3.55-fold among patients with generalized MG and type 2 DM increased the risk of not achieving remission by 9.32-fold among patients with ocular MG. Hypertension and type 2 DM had negative effects on the clinical outcomes of MG.

Age of onset and factors affecting treatment responses in ocular myasthenia gravis.

Ocular myasthenia gravis (OMG) is an autoimmune disease which causes ptosis, diplopia, or both. It can be categorized as early or late onset, with differing presenting characteristics and prognoses. Currently, there is limited information available to compare characteristics and outcomes in onset groups in Thailand. To describe and compare baseline characteristics and outcomes in OMG patients classified by onset groups and to investigate the factors associated with the disease, especially in terms of treatment responses classified according to the MGFA Post-Intervention Status (MGFA-PIS). OMG patients diagnosed between January 2014 and March 2021 at Rajavithi Hospital, Thailand, were categorized into 2 groups based on age of onset, and baseline characteristics were analyzed and compared. The treatment responses of each group in terms of time to achievement of minimal manifestations (MM) were analyzed. Eighty-one patients (38 with early and 43 with late onset) were included, and the mean (SD) follow-up time was 35.85months (17.25). There was no significant difference between the baseline characteristics of the two groups. A low dose of pyridostigmine was more commonly used in the early-onset group (p = 0.01), while the mean dose of corticosteroids was significantly lower in the late-onset patients (p < 0.001). We found that seropositivity of acetylcholine receptor antibody decreased the odds ratio of achievement of MM (OR 0.185, 95% CI 0.043-0.789, p = 0.023) and receiving a high dose of pyridostigmine (≥ 120mg/day) increased the odds ratio of achieving it (OR 8.296, 95% CI 2.136-32.226, p = 0.002). A higher dose of pyridostigmine may be necessary for achievement of favorable treatment response. AChRAb seropositivity is a predictor for unfavorable treatment response in Thai populations.

A cross-sectional study assessing the effectiveness of hygiene related interventions and education delivered in an afterschool club in urban slums of Gurugram

Background: There is insufficient evidence about the effectiveness of hygiene related interventions and education delivered to out of school children, attending non-formal schools in urban slums. Methods: This cross sectional, interventional study was conducted from January 2022 to April 2022 in a non-formal school in an urban slum in Gurugram, Haryana. A validated questionnaire about hygiene related practices was used to record the behavioural practices of these children before and after education about hygienic practices. The children were also provided with soap, detergent, and four sets of clothes to enable them to follow the hygienic practices. The pre and post intervention status of various hygiene variables was compared. A p&lt;0.01 was considered as statistically significant. Results: Of the 97 children included in this interventional study, 54 were boys. All of them were from the lower socioeconomic class, with 93% of the mothers and 98% of the fathers being illiterate. The percentage of unhygienic practices decreased significantly post intervention. All the p values for comparison between the pre and post intervention status of various hygiene variables were highly significant statistically (p=0.001). Maximum improvement was seen in case of brushing teeth, cutting nails, using footwear and bathing (2.86). Similarly, the total mean score for pre intervention was 30.62 which decreased to 10.54, indicating a total improvement of 20.08. Conclusions: Hygiene related interventions including continuing education, and provision of clothes and detergent, can improve hygienic practises in out of school children who attend non-formal schools in slums.

The Duke Myasthenia Gravis Clinic Registry: II. Analysis of outcomes.

The Duke Myasthenia Gravis (MG) Clinic Registry contains comprehensive physician-derived data on patients with MG seen in the Duke MG Clinic since 1980. The aim of this study was to report outcomes in patients seen in the clinic and treated according to the International Consensus Guidance statements. This is a retrospective cohort study of patients initially seen after 2000 and followed for at least 2 years in the clinic. Treatment goal (TG) was defined as achieving MGFA post-intervention status of "minimal manifestations" or better; PIS was determined by the treating neurologist. Time-to-event analysis, including Cox proportional hazards modeling, was performed to assess the effect of sex, acetylcholine receptor antibody (AChR-Ab) status, age at disease onset, distribution (ocular vs generalized), thymectomy, and thymoma on the time to achieve TG. Among the 367 cohort patients, 72% achieved TG (median time less than 2 years). A greater proportion of patients with AChR-Abs and thymectomy achieved TG and they did so sooner than patients without these antibodies or thymectomy. Otherwise, there were no significant differences in these findings within the tested subgroups. The disease duration at the first Duke Clinic visit was shorter in patients who achieved TG than in those who did not. These results demonstrate outcomes that can be achieved in patients with MG treated according to the current Consensus Guidance statements. Among other things, they can be used to determine the added value and potential role of new treatment modalities developed since 2018.

Reduced quality of life in myasthenia gravis patients: A study on 185 patients from China.

To explore the quality of life (QOL) in patients with myasthenia gravis (MG) and factors associated with QOL. This observational study included patients with MG diagnosed at the First Affiliated Hospital of Fujian Medical University between January 2020 and March 2022. The QOL of patients was evaluated with the 15-item Myasthenia Gravis Quality of Life (MG-QOL15). Current MG severity was evaluated with MGFA grade, MG-ADL score, MGC score, and MGFA Postintervention Status. The data about gender, age of onset, subgroup, antibodies, age, duration, education, employment state, marital status, skeletal muscle affected, thymic histology, and current treatment methods of the patient were collected. A total of 185 patients [72 males (38.9%), aged 45.2 years (14-77)] with MG were enrolled. Age at onset was 38.3 ± 17.9 years, and disease duration was 87.9 months (0-672). The median MG-QOL15 score was 12.5 (0-58). The item "have trouble using my eyes" was the highest scoring item in both ocular and generalized patients with MG. The MG-QOL15 score was significantly different among patients with OMG (9.2 ± 9.4, n = 63), GMG (9.0 ± 8.8, n = 22), and BMG (15.4 ± 14.2, n = 100) (P = 0.018). Patients with BMG had higher MG-QOL15 scores than OMG (P = 0.001) and GMG (P = 0.009), but there was no significant difference between OMG and GMG (P = 0.467). The MG-QOL15 score was significantly lower in patients who had undergone thymectomy (9.7 ± 9.8, n = 58) compared to those who had not (13.8 ± 13.4, n = 127, P = 0.022). MG-QOL15 score was significantly lower in patients who underwent thymectomy compared to those who did not (9.7 ± 9.8, n = 58 vs. 13.8 ± 13.4, n = 127, P = 0.022). MG-QOL15 score was different among MGFA grades (Remission: 5.2 ± 5.4, n = 41; I: 11.3 ± 10, n = 61; II: 11.6 ± 11.1, n = 40; III: 18.1 ± 12.1, n = 29; and IVa: 30.1 ± 20, n = 14, P < 0.001). There was no significant difference between patients in MGFA grade I and II (P = 0.896), and there was no significant difference between patients in MGFA grade III and IVa (P = 0.052). MG-ADL (P < 0.001) and MGC (P < 0.001) were positively correlated with MG-QOL15. Men had higher MG-QOL15 than women (P = 0.094), and LOMG had higher MG-QOL15 than EOMG (P = 0.072). Multivariate linear regression identified that higher MG-ADL (P < 0.001), higher MGC (P = 0.02), and poor employment status (P = 0.045) were independently associated with higher MG-QOL15. Having trouble using the eyes accounted for the highest score in MG-QOL15, eye symptoms affect QOL more than limb weakness in MG. Daily life activity, disease severity, and employment status were associated with patients' QOL. Adequate treatment should be applied to improve QOL, while mild symptoms can be accepted. Men and patients over the age of 50 years of onset may need more attention.

Short-term outcome prediction for myasthenia gravis: an explainable machine learning model.

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigability. The fluctuating nature of the disease course impedes the clinical management. The purpose of the study was to establish and validate a machine learning (ML)-based model for predicting the short-term clinical outcome in MG patients with different antibody types. We studied 890 MG patients who had regular follow-ups at 11 tertiary centers in China from 1 January 2015 to 31 July 2021 (653 patients for derivation and 237 for validation). The short-term outcome was the modified post-intervention status (PIS) at a 6-month visit. A two-step variable screening was used to determine the factors for model construction and 14 ML algorithms were used for model optimisation. The derivation cohort included 653 patients from Huashan hospital [age 44.24 (17.22) years, female 57.6%, generalized MG 73.5%], and the validation cohort included 237 patients from 10 independent centers [age 44.24 (17.22) years, female 55.0%, generalized MG 81.2%]. The ML model identified patients who were improved with an area under the receiver operating characteristic curve (AUC) of 0.91 [0.89-0.93], 'Unchanged' 0.89 [0.87-0.91], and 'Worse' 0.89 [0.85-0.92] in the derivation cohort, whereas identified patients who were improved with an AUC of 0.84 [0.79-0.89], 'Unchanged' 0.74 [0.67-0.82], and 'Worse' 0.79 [0.70-0.88] in the validation cohort. Both datasets presented a good calibration ability by fitting the expectation slopes. The model is finally explained by 25 simple predictors and transferred to a feasible web tool for an initial assessment. The explainable, ML-based predictive model can aid in forecasting the short-term outcome for MG with good accuracy in clinical practice.

Relation of Demographic and Impact of Psych educational Program on Anxiety Level in Patient Diagnosed with Generalized Anxiety Disorder in Garmian Psychiatric Center/Kalar

Background and aim: anxiety disorders are among the most frequent psychiatric disorders that nearly one-third of the population is being affected by an anxiety disorder during their life. Psychoeducation has been used as the main anxiety management for patient diagnosed with anxiety disorder. The aim of the study to asses effectiveness of psycho- educational program among patients diagnosed with anxiety. Methodology: A quasi-experimental design was carried out on 82 patients diagnosed with anxiety disorder. The patients attended a knowledge-based psycho-educational program, and anxiety level was measured using the Zang anxiety self-rating scale in pre- post- intervention status . The data was analyzed using the statistical package for social sciences (SPSS) version (23). Result s: this study has demonstrated that anxiety was high among female (67.1%) and high educated (44.9%) comparatively. The study has also indicated that psychoeducation program has significant impact on decreasing the anxiety severity. The percentage of severe anxiety in pre-intervention state was (40.2%), mild and moderate anxiety level was (9.8%) and (50%) respectively, while in post-intervention status, severe anxiety level was (20.7%), mild and moderate anxiety level were (15.9%), (63.4%) respectively. Conclusion: This study concluded that psych-education intervention could significantly reduce level of anxiety among anxiety patients. The impact of a psychiatric education program is primarily due to increased knowledge about anxiety and improved problem-solving skills for anxiety sufferers. Anxiety was observed less frequent in male, single and less educated, while anxiety was more severe comparatively

A retrospective study of the safety and efficacy of rituximab in Iranian patients with myasthenia gravis: A single-center experience.

Background: This retrospective cohort study was conducted to evaluate the efficacy and tolerance of rituximab (RTX) for the management of myasthenia gravis (MG). Methods: This retrospective cross-sectional study was conducted on 61 patients with refractory and non-refractory MG who received RTX. The Myasthenia Gravis Activities of Daily Living (MG-ADL) profile was used to assess MG symptoms and their effects on daily activities at the start of RTX and in the last follow-up. The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) scale has been used as an outcome measure after treatment with RTX in the 12th month and the last follow-up. Results: The mean age of the patients was 40.31 ± 13.53 years (range: 15-78 years). Of 61 patients, eight (13.1%) were double seronegative, 29 (47.5%) had anti-acetylcholine receptor (AChR+) antibody, and 24 (39.3%) had anti-muscle-specific tyrosine kinase antibody (MuSK+). According to the mean rank table, the results of this study showed that the drug was more effective in improving the symptoms of MuSK+ patients compared to the other two groups (P = 0.006). The mean MG-ADL was 4.86 ± 1.83 before treatment and 1.51 ± 2.02 in the last follow-up visit. Paired t-test showed a significant association between MG-ADL before and after treatment in the last visit [t(55): 11.30, 95% confidence interval (CI): 2.79-3.99, P = 0.001)]. Conclusion: This retrospective study showed a considerable effect of RTX as induction therapy in patients with MG, especially those with MuSk+ MG.

Rituximab in Myasthenia Gravis- Experience from a Low- and Middle-Income Country (LMIC) Setting.

Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction. About 10% are refractory to immunosuppressive therapy. To analyze the response of patients with generalized MG to rituximab. A retrospective review of patients with MG who received rituximab was carried out (n = 13, M:F = 6:7, mean age: 44.84 ± 15.73 years). Myasthenia Gravis Foundation of America (MGFA), MGFA post-intervention status (MGFA-PIS), and Myasthenia Gravis Status and Treatment Intensity (MGSTI) were assessed before and after rituximab. The duration of MG was 104.07 ± 92.25 months. Before rituximab, the MGFA was IIA/IIB/IIIA/IIIB/IVB/V in 1/1/2/6/2/1 patients and MGSTI was four in eight patients and six in three patients. The mean duration of follow up was 20.92 ± 14.06 months (range, 4 to 42 months). Dose reduction or discontinuation of cholinesterase inhibitors could be achieved 12 patients. Complete stable remission (CSR) and pharmacologic remission (PR) were achieved in one and four patients respectively and five patients had minimal manifestations. Most patients attained level 0, 1 or 2 MGSTI at last follow up. No rituximab infusion-related adverse events were noted. Three patients had exacerbation of MG between one to five weeks after rituximab administration. Three patients died, one each due to a cardiac event unrelated to MG or treatment, complications related to myasthenic crisis, and coronavirus disease. Rituximab was effective in bringing about remission in MG and can be considered as a first-line agent. However, it has to be administered under close supervision as some patients develop exacerbation of MG akin to steroid-induced worsening.

Frailty Status Improvement after 5-Month Multicomponent Program PROMUFRA in Community-Dwelling Older People: A Randomized Controlled Trial.

A study was made of the effect of the PROMUFRA multicomponent frailty program upon physical frailty, kinanthropometry, pain and muscle function parameters in frail and pre-frail community-dwelling older people. Eighty-one participants were randomly allocated to the intervention group (IG) or control group (CG). The IG performed PROMUFRA for 20 weeks, using six strength exercises with three series of 8–12 repetitions until muscular failure, and seven myofascial exercises, with one set of 10 repetitions. The CG continued their routine. The frailty criteria number (FCN), kinanthropometric parameters and muscle function were measured at baseline and after the program. Between-group differences were found in the interaction for FCN, muscle mass, fat mass, skeletal muscle mass index, knee flexion range of motion (ROM), hip flexion with knee straight ROM, maximum isometric knee extension, maximum isotonic knee extension, maximum leg press and hand grip strength., and also on post-intervention frailty status. The IG showed a statistical trend towards decreased pain. In conclusion, the PROMUFRA program is a potential training approach that can bring benefits in physical frailty status, body composition, ROM and muscle function among frail or pre-frail community-dwelling older people.

Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia

The aim of this study is to evaluate the long-term efficacy, safety, and impact on immunoglobulin G (IgG) levels of rituximab in patients with myasthenia gravis (MG). A retrospective, observational study of drug-refractory MG patients treated with rituximab was done. The MG Foundation of America postintervention status (MGFA-PIS) was used to evaluate clinical response. Serum IgG levels were determined at baseline and post-treatment. Hypogammaglobulinemia was defined as IgG<7g/L. Thirty patients were included, 12 with anti-MuSK and 18 with anti-AChR antibodies. Mean (SD) follow-up was 85.5 (48) months. All 12 MuSK+ patients but only six (33%) AChR+ patients achieved minimal manifestations or remission (p<0.01). Nine severe infections were observed in five patients (17%). One patient was diagnosed with progressive multifocal leukoencephalopathy. At baseline, two patients (2/24; 8%) had hypogammaglobulinemia. During follow-up, hypogammaglobulinemia was observed in 60% (3/5) of patients who developed an infection and in 33% (7/21) who did not. Two of these patients died of infection-related complications. This study supports the effectiveness of rituximab in patients with MG, especially those with anti-MuSK antibodies. Severe infections may appear after rituximab treatment and hypogammaglobulinemia might play a role on it. A standard protocol would be needed to closely monitor IgG levels in MG patients treated with rituximab.

Minimal Manifestation Status Indicates a Stable State in Myasthenia Gravis: A Quantitative Study.

IntroductionMinimal manifestation (MM) or better was recommended as the treatment goal for myasthenia gravis (MG). The sustainability of this status has not been described quantitatively in patients who had attained or are close to it.MethodsPatients who were with no or slight impact on daily living were recruited and followed at baseline and 3, 6, and 12 months. The included patients were classified into 3 post-intervention status (PIS) categories: remission (R), MM, and slight impact (SI). The proportion of patients belonging to real-time (not considering the intervals between assessments) and sustained (considering the intervals between assessments) PIS categories was compared at each follow-up. A sensitivity analysis (SA) cohort was established by including patients with PIS categories in all four follow-ups. The QMGS, MG-ADL, and MG-QOL15 scores in patients belonging to each PIS category at each follow-up were compared. The sustainability of the R/MM status was examined and correlated with real-time R/MM status at follow-ups.ResultsAt baseline, 376 patients could be classified, including 55 as R (14.2%), 209 as MM (54.0%), and 112 as SI (28.9%). In the whole cohort, 68.8–89.7%, 71–76.7% and 19.8–77.1% of the patients classified into real-time R, MM, and SI categories remained unchanged in each follow-up compared with the previous follow-up. The proportion of patients belonging to each real-time or sustained R/MM status at the three follow-ups was 89.7–92.1 or 60.8–67. In the SA cohort, at least 86.4% of the baseline R/MM patients remained in R/MM status till 12 months. There were no differences in keeping real-time R/MM status at 6 or 12 months between patients with and without sustained R/MM status at 3 and 6 months. There were differences in the QMGS, MG-ADL, and MG-QOL15 scores among patients belonging to each real-time category at baseline and follow-ups, ranking as R < MM < SI. The same trend was observed in patients belonging to each sustained PIS category with smaller scores than the same items of real-time categories.ConclusionThe sustainability of the R/MM status was confirmed. The R/MM status indicated a stable state of MG. The QMGS, MG-ADL, and MG-QOL15 scores may provide a quantitative reference for these PIS.

Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study.

PurposeTo evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients.Patients and MethodsWe retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up.ResultsClinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise.ConclusionLow-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.

Efficacy and Safety of Tacrolimus Therapy for a Single Chinese Cohort With Very-Late-Onset Myasthenia Gravis.

Background and PurposePrevious studies have found tacrolimus to be a favorable drug for treating different types of myasthenia gravis (MG), but few have focused on very-late-onset MG (VLOMG). This study evaluated the efficacy and safety of tacrolimus for VLOMG therapy.MethodsThis was a retrospective single-center cohort study of 70 patients with VLOMG (onset ≥65 years) who visited Peking University First Hospital in 2019. Participants were divided into the tacrolimus (Tac) group and the control group based on tacrolimus usage. We further divided the Tac group into patients treated without corticosteroids and with corticosteroids. Sociodemographic features, clinical profiles, and outcomes were compared between different therapies and further analyzed by multivariate regression. Details of tacrolimus treatment, comorbidities, and adverse drug reactions (ADRs) were described.ResultsAmong 70 patients, the median (interquartile range) age at onset was 71 (68–77) years, and the follow-up duration was 27 (27-29) months. Most patients were types I (28%) and III (40%) according to the MG Foundation of America (MGFA) classification. In the Tac group, tacrolimus treatment was maintained for 36 (27-38) months. The dosage at the final evaluation was 1.0 (1.0–1.75) mg/day, and the last blood concentration test was 4.25 (2.85–5.7) ng/ml. A total of 43% reached remission, and 37% improved based on MGFA postintervention status (MGFA-PIS). For the 9 patients, newly diagnosed at enrollment within this group, MG activities of daily living (MG-ADL) decreased significantly from 3 (2-5) to 2 (1-2) (p = 0.041). Regarding the 13 patients, coadministering Wuzhi capsules the tacrolimus concentration increased from 2.75 (1.4–3.8) ng/ml to 5.95 (5.1–7.0) ng/ml (p = 0.012). No significant differences in outcomes were observed between tacrolimus treatment without and with corticosteroids or between the Tac group and the control group. A total of 93% had at least one comorbidity. ADRs related to tacrolimus emerged in 25% (9/36) of patients, most of which were not serious and reversible.ConclusionsTacrolimus is effective and safe in treating VLOMG. Tacrolimus monotherapy without corticosteroids can be used as an initial and maintenance treatment for VLOMG. Wuzhi capsules work well in elevating tacrolimus concentrations in this population.

Physical and mental fatigue in myasthenia gravis and its correlation with other symptoms.

Muscle weakness and easy fatigability are the clinical hallmarks of myasthenia gravis (MG). However, fatigue perception, which can be seen quite often in myasthenic patients, and its effect on the quality of life, irrespective of motor deficit, has not been elucidated yet. The aim is to evaluate the frequency of fatigue in myasthenic patients with nearly full muscle strength and the effect of fatigue on quality of life by assessing its correlation with other symptoms. Fifty-three patients with ocular or mild generalized MG in remission or minimal manifestations completed the questionnaires measuring the severity of MG and quality of life (MG Composite Scale and MG-Activities of Daily Living Profile). Both patient group and control group (53 healthy volunteers)completed the scales assessing fatigue [Fatigue Assessment Scale (FAS) and Fatigue Impact Scale (FIS)], depression [Beck Depression Inventory (BDI)] and sleep (Epworth Sleepiness Scale). Disease severity was assessed using MG Foundation of America (MGFA) and MGFA Post-Intervention Status classifications. FAS, FIS physical and BDI scores were significantly higher in patients compared to the control group (p = 0.003, p = 0.001, and p = 0.003, respectively) and fatigue was associated with depression and daytime sleepiness. Inpatient group, depressive symptoms and daytime sleepiness were higher in females (p = 0.019 and p = 0.013). The mean values of FIS total and cognitive scores were higher in patients with generalized MG (p = 0.033 and p = 0.045). Fatigue scores correlated with motor signs. Fatigue can be seen in MG independently from muscle weakness and is an important symptom worsening the quality of life.

A School Intervention's Impact on Adolescents' Health-Related Knowledge and Behavior.

BackgroundMany factors can influence health behavior during adolescence, and the lifestyle of adolescents is associated with health behavior during adulthood. Therefore, their behavior can determine not only present, but also later health status.ObjectiveWe aimed to develop an intervention program to improve high school students' health behavior and to evaluate its effectiveness.MethodsWe performed our study at a secondary school in a rural town in East Hungary between 2016 and 2020. Sessions about healthy lifestyles were organized regularly for the intervention group to improve students' knowledge, to help them acquire the right skills and attitudes, and to shape their behavior accordingly. Data collection was carried out via self-administered, anonymous questionnaires (n = 192; boys = 49.5%; girls = 50.5%; age range: 14–16). To determine the intervention-specific effect, we took into account the differences between baseline and post-intervention status, and between the intervention and control groups using individual follow-up data. We used generalized estimating equations to assess the effectiveness of our health promotion program.ResultsOur health promotion program had a positive effect on the students' health-related knowledge and health behavior in the case of unhealthy eating, moderate to vigorous physical activity, and alcohol consumption.ConclusionOur findings suggest that school health promotion can be effective in knowledge transfer and lifestyle modification. To achieve a more positive impact on health behavior, preventive actions must use a complex approach during implementation.