Disease Duration Research Articles

Patient trust, quality communication, and medication adherence in rheumatoid arthritis patients highly affected by social determinants of health.

Because medication adherence is essential to the management of rheumatoid arthritis (RA), identifying (1) subgroups at high risk for low medication adherence and (2) modifiable factors potentially contributing to low adherence can impact patient outcomes. This study aims to describe the relationships between anxiety, trust in the provider, quality patient-provider communication, fatigue, RA knowledge, adverse medication effects, disease activity, RA medications, disease duration, patient satisfaction, and medication intolerance and cluster factors to differentiate RA-patient subgroups. This observational study used correlation analysis, linear regression, and cluster analysis with determination decisions based on Schwarz's Bayesian Criterion. Medication adherence was higher in non-Hispanic, White participants, inversely correlated with disease activity and pain intensity, and positively correlated with trust in the provider. Patient satisfaction was higher among those with a shorter time since diagnosis, and was negatively associated with disease activity, pain intensity and interference, fatigue, and anxiety. It was positively associated with RA knowledge, trust in provider and quality of patient-provider communication. Medication intolerance differed by disease duration and was positively correlated with disease activity, pain interference, and fatigue. Of the two clusters, Cluster 1 participants had greater medication adherence and patient satisfaction, and lower medication intolerance. They were of higher income, employed, and non-Hispanic, White persons with a shorter disease duration and lower perceived pain intensity/interference, fatigue, and anxiety. They were more knowledgeable about RA with higher trust in their provider and perceived quality of patient-provider communication. A low medication adherence RA-patient subgroup-highly affected by social determinants of health and with unique relational and clinical characteristics was identified.

Gender-driven thyroid dysfunction in systemic lupus erythematosus patients: Clinical significance of an overlooked association and global stance

Aim of the workThis study aimed to determine the association of thyroid dysfunction in systemic lupus erythematosus (SLE) patients Patients and methodsOut of a cohort including 312 adult SLE patients those with thyroid dysfunction (n = 53) were further evaluated. The medical history, clinical examination, laboratory investigations and medications received were recorded. The SLICC damage index (SLICC-DI) was assessed. ResultsThyroid dysfunction formed 17 % of the patients and their mean age was 39.5 ± 11.5 years and disease duration 5.6 ± 3.3 years were comparable to those without thyroid disorder, however female gender was predominantly higher (F:M 52:1 vs 6.2:1, p < 0.0001). The frequency of thyroid dysfunction was alike in Saudi (16 %) and non-Saudi (17.9 %) patients (p = 0.66). The majority of cases (96.2 %) had hypothyroidism, one with autoimmune thyroiditis, while only 2 (3.8 %) had hyperthyroidism. There was a significantly increased frequency of associated neuropsychiatric manifestations (64.2 % vs 45.2 %;p = 0.012), and hematological involvement (32.1 % vs 14.3 %; p = 0.011) and less complement (C4) consumption (15.1 % vs 23.6 %; p = 0.048) in those with thyroid dysfunction compared to those without. The frequency of anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity tended to be higher (71.7 % vs 66.8 %) and its titre significantly lower (316.3 ± 319.8 IU/ml vs 461.3 ± 459.1; p = 0.013). The SLICC-DI and mortality rate were comparable between groups. Only the presence of proteinuria inversely significantly correlated with the level of T4 (r = -0.31, p = 0.007). ConclusionThyroid dysfunction forms a notable percentage of SLE patients with a prominent female gender propensity. The significant relation of thyroid disorders to neuropsychiatric manifestations, hematological involvement, C4 consumption and anti-dsDNA deserves recognition.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study

Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30×109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50×109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50×109/L or ≥100×109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30×109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n=4), zuberitamab 100mg (n=10), 300mg (n=8) and 600mg (n=10) groups. The primary endpoint (PLT ≥50×109/L at week 8) was achieved by 40% of patients in the 100mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50×109/L or ≥100×109/L or an increase twice more than baseline as well as ≥30×109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100mg-600mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600mg group, but gradually recovered at week 20. Three patients (2 in 100mg and 1 in 600mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA+patients may have higher response rates. This study preliminarily confirmed that 100mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Progression of valve heart disease in a cohort of patients undergoing renal replacement therapy.

Cardiovascular disease is an important cause of death among patients with chronic kidney disease (CKD). Valve calcification is a predictor of cardiovascular mortality and coronary artery disease. To assess heart valve disease frequency, associated factors, and progression in CKD patients. We conducted a retrospective study on 291 CKD patients at Hospital das Clínicas de Pernambuco. Inclusion criteria were age ≥ 18 with CKD and valve disease, while those on conservative management or with missing data were excluded. Clinical and laboratory variables were compared, and patients were categorized by dialysis duration (<5 years; 5-10 years; >10 years). Statistical tests, including chi-square, Fisher's exact, ANOVA, and Kruskal-Wallis, were employed as needed. Simple and multivariate binary regression models were used to analyze valve disease associations with dialysis duration. Significance was defined as p < 0.05. Mitral valve disease was present in 82.5% (240) of patients, followed by aortic valve disease (65.6%; 86). Over time, 106 (36.4%) patients developed valve disease. No significant association was found between aortic, pulmonary, mitral, or tricuspid valve disease and dialysis duration. Secondary hyperparathyroidism was the sole statistically significant factor for mitral valve disease in the regression model (OR 2.59 [95% CI: 1.09-6.18]; p = 0.031). CKD patients on renal replacement therapy exhibit a high frequency of valve disease, particularly mitral and aortic valve disease. However, no link was established between dialysis duration and valve disease occurrence or progression.

Characterization of tirzepatide-treated patients achieving different glycemic control levels in SURPASS-AP-Combo.

The study objective was to characterize subgroups of Asia-Pacific patients with type 2 diabetes who achieved different glycated hemoglobin (HbA1c) targets on tirzepatide treatment. This was a post hoc analysis of the SURPASS AP-Combo study. Baseline characteristics, changes in metabolic markers, and safety were compared between tirzepatide-treated patients achieving HbA1c <7.0% (<53 mmol/mol) and those achieving ≥7.0% (≥53 mmol/mol) at week 40. Among patients achieving HbA1c <7.0% (<53 mmol/mol), further comparisons were conducted among subgroups achieving HbA1c <5.7% (<39 mmol/mol), 5.7% to 6.5% (39 to 48 mmol/mol), and >6.5% to <7.0% (>48 to <53 mmol/mol). Five hundred ninety-eight patients on tirzepatide treatment without rescue medication were included (56.9% male; mean age: 53.1 years; mean baseline HbA1c: 8.7% [71.6 mmol/mol]). Patients achieving HbA1c <7.0% (<53 mmol/mol) versus ≥7.0% (≥53 mmol/mol) were slightly younger with a shorter disease duration and lower HbA1c at baseline, and they had greater improvements in HbA1c, fasting serum glucose, body weight, BMI, waist circumference, waist-height ratio, diastolic blood pressure, lipids, and self-monitored blood glucose at week 40. Patients achieving HbA1c <5.7% (<39 mmol/mol) versus those achieving 5.7% to 6.5% (39 to 48 mmol/mol) and those achieving >6.5% to <7.0% (>48 to <53 mmol/mol) were much younger, had much lower HbA1c, and had further improvements in metabolic markers. Tirzepatide treatment was well tolerated irrespective of the HbA1c level achieved, with a low incidence of hypoglycemic events. These findings may help to inform clinical decisions in Asia-Pacific patients with type 2 diabetes.

Efficacy of antioxidants in the management of psoriasis: A case control study

Introduction: Psoriasis is a chronic, immune-mediated inflammatory dermatosis. The pathophysiology of the disease is still incompletely elucidated and multiple factors are said to be involved in its initiation and perpetuation, e.g., stressors, genetic factors, environmental factors. In the last decade, a new theory is trying to explain the pathophysiology of this disease by looking at the role played by oxidative stress and chronic inflammation in the initiation of keratinocyte proliferation and differentiation. Keeping in consideration the increased oxidative stress in the patients of psoriasis, the anti-oxidant drugs can form an important part of the therapeutic ladder of psoriasis. Materials and Methods: The aim of this study was to measure the possible role of oxidative stress in psoriasis patient by measuring SOD level and comparing it with normal individuals and administer antioxidants supplements to the patients group to see the efficacy. It was a Case- Control study (1st part) and Clinical Trial without control group (2nd part). The study was carried out in Psoriasis awareness Club from June 2023 to December 2023. Purposive sampling done who fulfill the inclusion &amp; exclusion criteria. 23 patients with psoriasis and 23 age and sex matched control subjects were recruited for this study. Clinical severity of the disease was determined by PASI score. All patients and control subjects were examined for plasma SOD level. 23 psoriatic patients were given antioxidant therapy in the form of once daily tablet for 30 days. PASI score, DLQI and SOD (Superoxide dismutase) level were measured before therapy (day 0) and after therapy (day 30) in patients group. Statistical analysis and Results: Data were expressed as mean ± standard deviation (SD) for quantitative variables and numbers. For comparison of two means (t test) and (ANOVA "F") test were used for several means. Chi-square (χ2 ) or fisher exact test were used when appropriate, (P&lt;0.05) was considered statistically significant. The mean age of the patients and control subjects were 37.64 (±5.89) and 33.6 (11.02) years, respectively. The mean duration of the disease was 12.43 (±8) years. No significant difference was observed between SOD level of psoriatic patients &amp; controls. No significant correlations of SOD level with severity of psoriasis and duration of disease were found. We observed no statistically significant difference in PASI and DLQI scores before and after antioxidant therapy but there was significant increase in the level of SOD after treatment. Conclusion: It is indisputable that antioxidant supplementation can reduce the overall morbidity, enhance the prognosis of psoriasis. Notably, in most cases, antioxidants alone are not able to induce significant clinical changes in the aspect and/or course of the disease, except perhaps in mild forms. They must be used in conjunction with standard pharmacological treatments to achieve measurable results.

A machine learning-based diagnosis modeling of IgG4 Hashimoto's thyroiditis.

This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto's thyroiditis (HT) patients. A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT. Among these 272 patients, 40 (14.7%) were diagnosed with IgG4 HT. Patients with IgG4 HT were younger than those with non-IgG4 HT (P < 0.05). Serum levels of TgAb IgG4 and TPOAb IgG4 in IgG4 HT group were significantly higher than those in non-IgG4 HT group (P < 0.05). There were no significant differences in gender, disease duration, goiter, preoperative thyroid function status, preoperative TgAb or TPOAb levels, and thyroid ultrasound characteristics between the two groups (all P > 0.05). The accuracy, sensitivity, and specificity were 57%, 78%, and 79% for logistic regression model of IgG4 HT, 80 ± 7%, 84.7% ± 2.6%, and 75.4% ± 9.6% for the RF model and 78 ± 5%, 89.8% ± 5.7%, and 64.7% ± 5.7% for the SVM model. The RF model works better than SVM. The area under the ROC curve of RF ranged 0.87 to 0.92. A clinical diagnosis model for IgG4 HT established by RF model might help the early recognition of the high-risk patients of IgG4 HT.

DXA-derived lumbar bone strain index corrected for kyphosis is associated with vertebral fractures and trabecular bone score in acromegaly.

The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis (i.e., higher BSI indicates a lower bone's resistance to loads with consequent higher risk of fractures). We aimed to investigate the association between lumbar BSI and vertebral fractures (VFs) in acromegaly. Twenty-three patients with acromegaly (13 males, mean age 58 years; three with active disease) were evaluated for morphometric VFs, trabecular bone score (TBS), bone mineral density (BMD) and BSI at lumbar spine, the latter being corrected for the kyphosis as measured by low-dose X-ray imaging system (EOS®-2D/3D). Lumbar BSI was significantly higher in patients with VFs as compared to those without fractures (2.90 ± 1.46 vs. 1.78 ± 0.33, p = 0.041). BSI was inversely associated with TBS (rho -0.44; p = 0.034), without significant associations with BMD (p = 0.151), age (p = 0.500), BMI (p = 0.957), serum IGF-I (p = 0.889), duration of active disease (p = 0.434) and sex (p = 0.563). Lumbar BSI corrected for kyphosis could be proposed as integrated parameter of spine arthropathy and osteopathy in acromegaly helping the clinicians in identifying patients with skeletal fragility possibly predisposed to VFs.

An analysis of urodynamic parameters in diabetic and nondiabetic women.

Diabetes is highly prevalent worldwide, with an estimated 536 million living with diabetes in 2021, and that number projected to increase to 783 million by 2045. Diabetic bladder dysfunction is thought to affect up to 60%-90% of individuals with diabetes and can significantly impact quality of life. Despite the prevalence of diabetic bladder dysfunction, the exact pathophysiological mechanism, and resulting clinical presentation, remains debated. Our objective was to compare urodynamic parameters between diabetic and nondiabetic women, assessing the impact of various markers of diabetes severity on bladder function. A retrospective chart review was conducted on female patients aged 18 and above who underwent urodynamic studies at a single tertiary care university hospital system from 2014 to 2020. Patients were categorized based on diabetes status, and diabetes severity including duration of disease, hemoglobin A1c levels, insulin dependence, and markers of end-organ dysfunction. Urodynamic variables, including compliance, bladder voided efficiency, bladder contractility index, postvoid residual, maximum flow rate, capacity, voided volume, and detrusor overactivity, were assessed by two independent reviewers. Statistical analyses were performed to assess the impact of diabetes and diabetic severity on urodynamic parameters. A total of 652 female patients were included in the study, of which, 152 (23.3%) had diabetes, with an average duration of diagnosis of 82.3 months. Diabetic women were older and had higher body mass index compared to nondiabetic women. Diabetic retinopathy and neuropathy were present in 18% and 54.6% of diabetic patients, respectively. Significant differences in urodynamic parameters were observed between diabetic and nondiabetic women, with diabetic women showing higher rates of detrusor overactivity (p = 0.01), particularly associated with increasing BMI (p = 0.03). However, classic markers of diabetes severity including duration, as well as markers of end-organ damage, showed mixed associations with urodynamic changes. Despite the prevalence of diabetic bladder dysfunction and its impact on patient quality of life, the exact mechanisms and clinical presentation remain elusive. Our study highlights the significant differences in urodynamic parameters between diabetic and nondiabetic women, emphasizing the need for further research into the relationship between diabetes and diabetic bladder dysfunction.

The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records

BackgroundThis study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.MethodsIn UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered.ResultsT2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis (β=0.51\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta =0.51$$\\end{document}, 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13–1.19) times higher in post-T2D MDD individuals.ConclusionsThe timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Oropharyngeal Dysphagia Phenotypes Across Huntington’s Disease Stages: Endoscopic Findings and Tongue Pressure Analysis

Background: Oropharyngeal dysphagia (OD) is a common symptom in Huntington’s disease (HD) and is associated with severe health and psychosocial consequences. Different OD phenotypes are defined on the basis of characteristic patterns at fiberoptic endoscopic evaluation of swallowing (FEES), and they may vary during disease progression. Objective: To describe OD phenotypes in different HD stages and to analyze their association with neurological data and tongue pressure measurements. Methods: Twenty-four patients with HD at different stages of disease progression underwent a FEES. Data on penetration/aspiration, pharyngeal residue, and OD phenotypes were gained. Neurological examination was performed with the Unified Huntington’s Disease Rating Scale (UHDRS). Patient Maximum tongue pressure (MTP) and tongue endurance were measured. Results: We confirmed that the occurrence of penetration/aspiration increased with disease duration and pharyngeal residue increased from 16.7% to 100% , respectively. The most common OD phenotypes were oropharyngeal dyspraxia (91.7% ), posterior oral incontinence (87.5% ), and delayed pharyngeal phase (87.5% ). These types of dysfunctions are already detectable in &gt;80% of patients in the early disease stages. In more advanced stages, we also observed propulsion deficit (66.7% ), resistive issue (54.2% ), and protective deficit (37.5% ). Propulsion deficit was associated with higher disease stage, greater motor dysfunction (UHDRS-I), and lower MTP and tongue endurance (p &lt; 0.05). Conclusions: OD in HD results from a combination of different swallowing phenotypes. Early assessment of swallowing and periodical follow-ups are necessary to monitor OD severity and phenotypes and to revise diet recommendations.

Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

Vaccination status and self-reported side effects after SARS-CoV-2 vaccination in relation to psychological and clinical variables in patients with multiple sclerosis

The recent SARS-CoV-2 pandemic and the vaccination campaign posed a challenge to patients with autoimmune disease, such as multiple sclerosis (MS). We aimed for investigating whether psychological/sociodemographic/clinical characteristics of MS patients are associated with SARS-CoV-2 vaccination status and self-reported vaccination side effects (SEs). We have asked patients with MS about their willingness to receive recommended standard vaccinations pre-pandemically since June 2019. Between 10/2021 and 01/2022, we surveyed 193 of these MS patients about their current SARS-CoV-2 vaccination status, their perception of vaccination-related SEs, and reasons for and against SARS-CoV-2 vaccination. 75.6% of the patients declared their willingness to receive standard vaccinations before the pandemic. 84.5%, 78.2%, and 13.0% of the patients had received the first, second, and third SARS-CoV-2 vaccination, respectively, until the follow-up survey. The most common reason for not getting vaccinated against SARS-CoV-2 was concern about possible side effects (82.1%), followed by the belief that the vaccines had not been adequately tested (64.3%). Vaccination-related SEs were reported by 52.8% of the patients. Younger age, higher education, lower degree of disability, relapsing disease course, shorter disease duration, not receiving a disease-modifying therapy and higher anxiety and depression levels were associated with the occurrence of certain vaccination-related SEs. Concerns about novel vaccines are widespread among MS patients and necessitate targeted education of the patients, especially to those with more severe psychopathological symptoms (anxiety or depression) and those who are generally skeptical of vaccination.

Genetic analysis and natural history of Parkinson's disease due to the LRRK2 G2019S variant.

The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and natural history of carriers. We performed a 3.5-year prospective longitudinal online study in a large number of 1286 genotyped LRRK2 G2019S carriers and 109 154 controls, with and without PD, recruited from the 23andMe Research Cohort. We collected self-reported motor and non-motor symptoms every 6 months, as well as demographics, family histories and environmental risk factors. Incident cases of PD (phenoconverters) were identified at follow-up. We determined lifetime risk of PD using accelerated failure time modelling and explored the impact of polygenic risk on penetrance. We also computed the genetic ancestry of all LRRK2 G2019S carriers in the 23andMe database and identified regions of the world where carrier frequencies are highest. We observed that despite a 1 year longer disease duration (P = 0.016), LRRK2 G2019S carriers with PD had similar burden of motor symptoms, yet significantly fewer non-motor symptoms including cognitive difficulties, REM sleep behaviour disorder (RBD) and hyposmia (all P-values ≤ 0.0002). The cumulative incidence of PD in G2019S carriers by age 80 was 49%. G2019S carriers had a 10-fold risk of developing PD versus non-carriers. This rose to a 27-fold risk in G2019S carriers with a PD polygenic risk score in the top 25% versus non-carriers in the bottom 25%. In addition to identifying ancient founding events in people of North African and Ashkenazi descent, our genetic ancestry analyses infer that the G2019S variant was later introduced to Spanish colonial territories in the Americas. Our results suggest LRRK2 G2019S PD appears to be a slowly progressive predominantly motor subtype of PD with a lower prevalence of hyposmia, RBD and cognitive impairment. This suggests that the current prodromal criteria, which are based on idiopathic PD, may lack sensitivity to detect the early phases of LRRK2 PD in G2019S carriers. We show that polygenic burden may contribute to the development of PD in the LRRK2 G2019S carrier population. Collectively, the results should help support screening programmes and candidate enrichment strategies for upcoming trials of LRRK2 inhibitors in early-stage disease.

Changes in biomarkers of lipid in juvenile idiopathic arthritis and its association with various disease parameters: a 6-month follow-up study

Background: The objectives of our study were to determine the changes in lipid profile (total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C)) in juvenile idiopathic arthritis (JIA) and assess its association with epidemiological and clinical profile of JIA patients. Methods: This observational study was performed with 46 patients at presentation followed by 38 cases at 3 months and 18 cases at 6 months of follow up. Their demographic profile and clinical parameters including juvenile disease activity score (JADAS 27) were compared with the biomarkers of lipid profile. Results: The mean (SD) age was 105.85 (20.23) months at first visit with mean (SD) disease duration being 15 (6.4) months. Twenty-six participants had oligoarthritic (56.5%), while the rest had polyarthritis (43.4%). Most of the patients had borderline raised TG and LDL-C (cases with raised TG n=14 (30.4%), 12 (31.5%), 5 (27.7%) at 1st visit, 3 months, and 6 months respectively and LDL-C n=12 (26%), 10 (26.3%), 6 (33.3%) at 1stvisit, 3 months, and 6 months respectively). HDL-C level was low in 36 (78.2%) cases at first visit, 28 cases (73.6%) at 3 months and 12 cases (66.6%) at 6 months respectively. Lipid profile was significantly affected by gender difference, duration of disease and drug therapy (p&lt;0.05). Significant association have been found between JADAS score and TGL level with p value 0.03. Conclusions: Children with JIA definitely suffer from dyslipidemia. Among the biomarkers of lipid profile, low level of HDL-C is one of the most important highlights of our study. Further studies can help to strengthen the findings and formulate necessary interventions at an early stage.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis – A Case-Control Study

Introduction. This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) pa- tients by evaluating sympathetic skin response (SSR). Materials and Methods. The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged &lt;60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an ab- sent response was considered abnormal SSR. Results. SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value &lt;0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. Conclusion. ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an associa- tion between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the as- sociation of abnormal SSR with disease severity, duration, and type.

Parkinson's Disease: Coping Strategies, Cognitive Restructuring and Deep Brain Stimulation.

Less is known concerning the evolution of coping strategies before and after deep brain stimulation (DBS) in Parkinson's disease (PD) patients. In a randomized controlled trial, coping was measured with the neurological version of the CHIP (Coping with Health Injuries and Problem) and the BriefCOPE in PD patients before ( T1: DBS - 2 months) and after (T2: + 3 months, T3: + 6 months) DBS. Patients (N = 50, age 59 ± 5.7 years, disease duration 9.54 ± 3.7 years) were randomised in 3 groups: CRTG (preoperative psychological preparation with cognitive restructuring), PIG (preoperative non structured interviews), and CG (no psychological preparation). Coping strategies are modulated by the time of evaluation. Some strategies are significantly more used preoperatively than postoperatively, as strategies about the research for information (CHIP: F = 16.14; P = .000; η2 = .095; BriefCOPE F = 5.71; P = .005; η2 = .066), emotional regulation (F = 3.29; P = .042; η2 = .029), and well-being searching (F = 4.59; P = .013; η2 = .043). Some other strategies appear more used post than preoperatively, as palliative coping (F = 5.57; P = .005; η2 = .064), humour (F = 3.35; P = .041; η2 = .0.35), and use of substance (F = 4.43; P = .015; η2 = .070). No other specific time, group or time per group interaction effect was found. Coping strategies are crucial for PD patients to adapt to the evolution of their parkinsonian state. Their consideration should be more systematic in the neurosurgical process, particularly when neurological symptoms would remain after DBS. More insights are needed concerning the evolution of coping strategies through DBS and the impact of a preoperative psychotherapy over them in preoperative PD patients.

Extraarticular manifestations of juvenile idiopathic arthritis and their impact on health-related quality of life.

The objective of this study is to investigate extraarticular manifestations (EAMs) in patients with juvenile idiopathic arthritis (JIA) and assess their impact on health-related quality of life (HRQoL) among these patients. This cross-sectional analytic study was carried out on 117 patients with JIA. EAMs were identified clinically by history and examination. Sicca symptoms, peripheral neuropathy, enthesitis, and skin lesions were picked up during clinical examination. Pulmonary involvement was evaluated by high-resolution CT chest. Patients were assessed by abdominal ultrasonography to assess the size of liver and spleen. Atlantoaxial subluxation was evaluated by cervical spine x-rays. Patients were evaluated by Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL-3 arthritis module. The median age of patients was 14years with a median disease duration 4years, 82.9% were females. Of the studied 117 JIA patients, 85 patients (72.6%) had at least one EAM. Persistent fatigue (51.3%) was the most prevalent EAM, followed by recurrent skin rash (16.2%), enthesitis (15.4%), recurrent fever (13.7%), and uveitis (12%). Patients with EAMs scored significantly lower in physical functioning (p = 0.001), emotional functioning (p < 0.001), social functioning (p = 0.005), and school functioning (p = 0.001). Regarding PedsQL arthritis module, patients with EAM had also significantly lower scores than did patients without EAM on the domains of pain and hurt (p < 0.001), daily activities (p = 0.008), and worry (p = 0.001). EAMs are prevalent among JIA patients and have a negative impact on their HRQoL. So, early identification and treatment are highly recommended. Key Points • A large percentage of JIA patients experienced at least one extraarticular manifestation (EAM). • Persistent fatigue and recurrent skin rash are the most prevalent EAMs in JIA patients. • JIA patients with EAMs have worse scores in almost all domains of HRQoL.

Risk factor analysis of vertebral fractures requiring surgery in patients with ankylosing spondylitis.

This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS). We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group. At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis. CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.