Longer Disease Duration Research Articles

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study

ObjectivesTo compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe.MethodsProspectively collected data on secukinumab-treated axSpA patients with...

The Burden of Chronic Obstructive Pulmonary Disease COPD in Stable Patients and its Association with Inflammatory Biomarkers and Body Mass Index

Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation that is preventable but not curable. It is associated with persistent symptoms that cause a considerable burden on individual productivity at work, and daily activities, and reduced quality of life, also burdening the healthcare system and society. Objectives: The study aims to measure the burden of COPD on patients in terms of daily activities and work productivity. It also seeks to investigate some inflammatory biomarkers' levels and their correlation with selected outcomes. Patients and Methods: A cross-sectional study on 120 stable COPD patients who were diagnosed and treated according to the GOLD guidelines at Kirkuk General Hospital's chest and Internal Medicine consultation clinics, and in private internist clinics in Kirkuk City, Iraq between January and April 2023. The Work Productivity and Activity Impairment Questionnaire (WPAI-COPD) measured the Burden of COPD. The symptom burden was assessed by the COPD assessment test (CAT). The level of IL-6 monoclonal antibodies was measured via a Roche Cobas 6000 analyzer and TNF-α using the ELISA sandwich technique. All these devices and machines were authorized by the Ministry of Health, Iraq. Results: The mean age was (54.1 ± 8.12) years, 62.5% being males and 37.5% being females; 41.7% were public sector employees, and 39.2% were self-employed. Due to COPD, the overall work loss was (45.9±18.91) days, the mean percentage of absenteeism was (10.9% ± 12.31%), activity impairment was (47.5% ±17.79%) among all patients, presenteeism was (40.8 ± 15.05%,) and COPD-related retirees were 14.2% of the study group. The mean CAT score (19.3±5.63) was high and the most troubling symptom among patients was chest tightness. WPAI-COPD scores were higher in older age and longer disease duration. The levels of biomarkers were above the reference ranges, the mean IL-6 level was (69.4 ± 35.29) pg/ml, and the mean TNF-α was (72.3 ± 22.45) pg/ ml. Conclusions: COPD patients exhibit a disease burden in terms of productivity loss at work and activity impairment that increases with aging and disease duration. COPD patients with low BMI are more prone to a decline in lung functions and to worse symptoms.

Structural Lung Disease and Clinical Phenotype in Bronchiectasis Patients: The EMBARC CT Study.

Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3-7.7) for total BE, 4.2 (1.2-8.1) for total MP, 8.3 (3.5-16.7) for total inflammatory changes, and 14.9 (9.1-25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping.

Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development. To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI). This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection. Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise. Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated. Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs. The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Validation, Reliability, and Clinical Significance of the Arabic Version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire.

Clinically relevant fatigue in rheumatoid arthritis (RA) patients significantly affects their quality of life. Almost all studies have assessed fatigue in this population using non-specific scales. The present multi-centric study aimed to assess the validity, reliability, and clinical significance of the Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ). The present cross-sectional multicentric study was conducted at Aswan, Mansoura, Port Said, and Al-Azhar University Hospitals over a 6-month duration. The study included 311 patients with RA diagnosed according to the 2010 criteria of the American College of Rheumatology. The Arabic version of BRAF-MDQ was developed to assess fatigue in these patients. All patients were subjected to careful history taking, thorough clinical assessment, and standard laboratory work-up. The obtained Arabic BRAF-MDQ was tested for construct validity, internal consistency, testretest reproducibility, and criterion validity. Construct validity was evaluated using factor analysis with the Kaiser Meyer Olkin tool of sampling adequacy and Bartlett's sphericity test. Internal consistency of subscales was assessed using Cronbach's alpha. Test-retest reproducibility was assessed after a 1-week interval using the intraclass correlation coefficient. Pearson's correlation coefficient was used to correlate numerical variables. Predictors of fatigue were identified using binary logistic regression analysis. The present study included 311 RA patients. Construct validity assessment showed a high loading of questionnaire items within the proposed construct subscales with a KMO measure of sphericity of 0.927 and Bartlett's test of sphericity p-value < 0.001. Internal consistency assessment showed adequate Cronbach's alpha of Arabic BRAF-MDQ subscales. Total Arabic BRAFMDQ had excellent criterion validity, as indicated by the high correlations with MAFS (r=0.95, p < 0.001) and SF-36 vitality subscale (r=-0.91, p < 0.001). Clinically significant fatigue was identified in 214 patients (68.8%). Multivariate logistic regression analysis revealed age (OR (95% CI): 1.07 (1.02-1.12), p < 0.001), disease duration (OR (95% CI): 1.82 (1.43-2.33), p < 0.001), DAS28CRP (OR (95% CI): 8.62 (4.63-16.02), p < 0.001), and mHAQ (OR (95% CI): 3.85 (1.07-13.9), p = 0 .039) as significant predictors of fatigue development in the studied patients. The Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire is a valid, consistent, and reliable tool for the assessment of fatigue in Egyptian rheumatoid arthritis patients. Clinically significant fatigue was identified in 214 patients (68.8%). Further, risk factors for fatigue included older age, longer disease duration, and higher disease activity.

Insights into determinants of health-seeking behavior: a cross-sectional investigation in the Iraqi context.

Health-seeking behavior (HSB) is a choice taken by an individual to maintain, achieve, or restore good health and prevent diseases. The purpose of this study is to examine the determinants of HSB among the Iraqi population. This cross-sectional study in the Rusafa and Karkh districts of Baghdad investigated determinants of HSB from 2022 to 2023. With a sample size of 993 participants meeting inclusion criteria, data were collected through a self-reported questionnaire, utilizing four indicators to measure HSB. The study employed various statistical methods especially logistic regression models, facilitated by Stata 17 software. Results highlights that married individuals consistently have higher odds of having HSB compared to their single counterparts, with an odds ratio (OR) of 2.09 (95% confidence interval: 1.41-3.10). This relationship remains robust even after controlling for other variables. Furthermore, individuals with higher social class exhibit stronger connections to HSB, although the OR is 1.69 (95% CI: 0.47-6.13), indicating a wide confidence interval. Regarding underlying diseases and their duration, the results indicate that chronic diseases are associated with a higher likelihood of HSB, with an OR of 2.05 (95% CI: 1.35-3.11). Additionally, a longer duration of diseases in terms of years is also linked to a stronger association with HSB, with an OR of 2.86 (95% CI: 1.32-6.23). In conclusion, this work provides important insights into HSB. Married people are continuously more likely to engage in HSB than single people, highlighting the importance of customized interventions. Furthermore, persons from higher social classes have stronger ties to HSB, highlighting the importance of socioeconomic considerations. The link between HSB and chronic diseases, combined with longer disease durations, emphasizes the importance of early detection and thorough healthcare management. These findings give critical guidance for healthcare providers, marketers, and politicians developing effective initiatives to promote HSB.

Dopa Responsiveness in Parkinson's Disease.

Dopaminergic responsiveness is a defining feature of Parkinson's disease (PD). However, there is limited information on how this evolves over time. To examine serial dopaminergic responses, if there are distinct patterns, and which factors predict these. We analyzed data from the Parkinson's Progression Markers Initiative on repeated dopaminergic challenge tests (≥24.5% defined as a definite response). Growth-mixture modeling evaluated for different response patterns and multinomial logistic regression tested for predictors of these clusters. 1525 dopaminergic challenge tests were performed in 336 patients. At enrolment, mean age was 61.2 years (SD 9.6), 66.4% were male and disease duration was 0.5 years (SD 0.5). 1 to 2 years after diagnosis, 48.0% of tests showed a definite response, but this proportion increased with longer disease duration (51.1-74.3%). We identified 3 response groups: "Striking" (n = 29, 8.7%); "Excellent" (n = 110; 32.7%) and "Modest" (n = 197, 58.6%). Significant differences were as follows: striking responders commenced treatment earlier (P = 0.02), were less likely to be on dopamine agonist monotherapy (P = 0.01), and had better cognition (P < 0.01) and activities of daily living (P = 0.01). Excellent responders had higher challenge doses (P = 0.03) and were more likely to be on combination therapy (P < 0.01). Three distinct patterns of the dopaminergic response were observed. As the proportion of PD cases with definite dopa responsiveness increased over time, the initial treatment response may be an unreliable diagnostic aid.

Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials

BackgroundSeizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies...

Level of insight in Egyptian patients having obsessive compulsive disorder: a comparative study

Background and objectivesObsessive–compulsive disorder (OCD) is a chronic psychiatric disorder defined by the existence of obsessions and/or compulsive behaviors or mental acts persistently and affects around 1–3% of the population in the world. Multiple studies demonstrated the link of the insight level to how severe was OCD and existence of resistance to both medications and psychotherapy in individuals with OCD. Studying the characteristics associated with poor insight is very important for management of treatment-resistant OCD and development of new therapeutic approaches. The purpose of this work was to assess the level of the insight in Egyptian patients with OCD, identify clinical correlates that could anticipate the degree of insight, and assess the validity and reliability of brown assessment of belief scale after being translated to Arabic version.MethodsA comparative cross-sectional study of 96 individuals (male and female aged from 18 to 60) diagnosed with OCD based on the Arabic version of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The study excluded any individuals with any coexisting neuro-psychiatric conditions and a history of major medical disease. Severity of OCD was assessed through the Arabic version of the Yale–Brown Obsessive–Compulsive Scale (YBOCS). Subsequently, participants performed the Brown Assessment of Beliefs Scale (BABS) after being translated into Arabic and assessed for reliability, validity and applicability of the translated form.ResultsPatients with OCD presented with poor insight were associated with more untreated time interval, longer disease duration and more severity that was dramatically differed (p ≤ 0.05, ≤ 0.001, ≤ 0.05 respectively). Also, there was a substantial notable correlation among BABS and YBOCS obsession, compulsion, and total score.ConclusionsThe existence of good insight in patients diagnosed with OCD was associated with lower severity and less duration of illness compared to patients with poor insight. Also, the more time waited before the intervention the worst the patient scores on the insight scale.

Association of Misfolded α-Synuclein Derived from Neuronal Exosomes in Blood with Parkinson's Disease Diagnosis and Duration.

Misfolded α-synuclein can be detected in blood samples of Parkinson's disease (PD) patients by a seed amplification assay (SAA), but the association with disease duration is not clear, yet. In the present study we aimed to elucidate whether seeding activity of misfolded α-synuclein derived from neuronal exosomes in blood is associated with PD diagnosis and disease duration. Cross-sectional samples of PD patients were analyzed and compared to samples of age- and gender-matched healthy controls using a blood-based SAA. Presence of α-synuclein seeding activity and differences in seeding parameters, including fluorescence response (in arbitrary units) at the end of the amplification assay (F60) were analyzed. Additionally, available PD samples collected longitudinally over 5-9 years were included. In the cross-sectional dataset, 79 of 80 PD patients (mean age 69 years, SD = 8; 56% male) and none of the healthy controls (n = 20, mean age 70 years, SD = 10; 55% male) showed seeding activity (sensitivity 98.8%). When comparing subgroups divided by disease duration, longer disease duration was associated with lower α-synuclein seeding activity (F60: p < 0.001). In the longitudinal analysis 10/11 patients showed a gradual decrease of α-synuclein seeding activity over time. This study confirms the high sensitivity of the blood-based α-synuclein SAA applied here. The negative association of α-synuclein seeding activity in blood with disease duration makes this parameter potentially interesting as biomarker for future studies on the pathophysiology of disease progression in PD, and for biologically oriented trials in this field.

Level of Anxiety Shows a Positive Correlation With the Frequency of Acute Cystitis Recurrence in Women.

Previous studies have simply confirmed recurrence of acute cystitis negatively affects a patient's psychological state. This study was performed to assess the impact of the recurrence of urinary tract infections on anxiety and depression and further assess whether there is a correlation between the number of recurrences and the degree of anxiety and depression. This cross-sectional study enrolled patients with recurrent cystitis who visited a tertiary care center between April 2018 and June 2022. For eligible patients, depression and anxiety were assessed by the Patient Health Questionnaire-9 and State-Trait Anxiety Inventory. Among the clinical characteristics, factors that independently affected the degree of depression and anxiety were analyzed. Additionally, the relationship between the level of anxiety, depression, and the number of recurrent cystitis was assessed. A total of 112 female patients with recurrent cystitis were enrolled in this study. The proportion of patients with depression (moderate, 8%; severe, 0%) was relatively low compared with that of patients with anxiety (moderate, 22.3%; severe, 68.8%). Multivariate regression analysis showed that more recurrent episodes were significantly associated with higher anxiety scores (P<0.001). It was confirmed that longer disease duration is associated with higher depression scores (P=0.031). Additionally, there was a positive correlation between the number of recurrences and State-Trait Anxiety Inventory and Patient Health Questionnaire-9 scores (r=0.362, P<0.001 and r=0.248, P=0.009, respectively). Our study reveals that recurrent cystitis notably increases patients' anxiety, correlating with the frequency of recurrences. Disease duration is also linked to depression. These findings emphasize the importance of preventing urinary tract infection recurrences to reduce psychological complications. To reinforce these results, larger cohort studies are necessary.

Real-World Data on the Effectiveness and Safety of Filgotinib for Ulcerative Colitis in Japanese Patients: A Single-Center Experience.

Introduction Filgotinib is a JAK-1 selective inhibitor approved for ulcerative colitis (UC) treatment in Japan. Its effectiveness has been confirmed but remains unknown in actual clinical practice. Therefore, we aimed to evaluate the effectiveness and safety of filgotinib and identify suitable patients in the Japanese population. Methods We retrospectively reviewed the background, clinical course, and laboratory data of patients treated with filgotinib 200 mg for UC between May 2022 and December 2023. Results The median observation period for the 25 patients was 232 days (interquartile ranges (IQR) 102-405). The median age of the patients was 43 years (IQR 29-55), disease duration was nine years (IQR 2-12), and 36% (9/25) of patients were biologic or small molecule naïve. The median patient-reported outcome (PRO2) and partial Mayo (pMayo) scores at agent initiation were 3 (IQR 1-4) and 4.5 (IQR 3-6), respectively. The PRO2 and pMayo scores improved significantly two weeks after treatment initiation (p < 0.05). Clinical remission rates at 24 weeks after treatment initiation were 60% (15/25) for PRO2 ≤ 1 and 52% (13/25) for pMayo ≤ 1. The Mayo endoscopic subscoresignificantly improved after filgotinib initiation (p=0.04), and the endoscopic remission rate was 47% (8/17). At 24 weeks, patients in clinical remission, compared to those not in remission, had significantly lower baseline PRO2 and pMayo scores and longer disease duration (p=0.03, p=0.03, and p=0.04, respectively). The filgotinib persistence rate was 68% (17/25), with no discontinuation because of adverse events. Patients who continued treatment had significantly lower PRO2, pMayo scores, and blood neutrophil counts at initiation than those who discontinued (p=0.02, p=0.03, and p=0.02, respectively). Conclusion Filgotinib appears to be effective and safe in Japanese patients with UC. Effectiveness and persistence were high in patients whose PRO2 and pMayo scores were low at the time of treatment initiation.

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.

High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38months) was significantly longer than that in patients without SM (9months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

Disentangling the heterogeneity of multiple sclerosis through identification of independent neuropathological dimensions

Multiple sclerosis (MS) is a heterogeneous neurological disorder with regards to clinical presentation and pathophysiology. Here, we investigated the heterogeneity of MS by performing an exploratory factor analysis on quantitative and qualitative neuropathology data collected for 226 MS donors in the Netherlands Brain Bank autopsy cohort. Three promising dimensions were identified and subsequently validated with clinical, neuropathological, and genetic data. Dimension 1 ranged from a predominance of remyelinated and inactive lesions to extensive pathological changes, higher proportions of active and mixed lesions, and foamy microglia morphology. This pattern was positively correlated with more severe disease, the presence of B and T cells, and neuroaxonal damage. Scoring high on dimension 2 was associated with active lesions, reactive sites, and the presence of nodules. These donors had less severe disease, a specific pattern of cortical lesions, and MS risk variants in the human leukocyte antigen region, the latter indicating a connection between disease onset and this neuropathological dimension. Donors scoring high on dimension 3 showed increased lesional pathology with relatively more mixed and inactive lesions and ramified microglia morphology. This pattern was associated with longer disease duration, subpial cortical lesions, less involvement of the adaptive immune system, and less axonal damage. Taken together, the three dimensions may represent (1) demyelination and immune cell activity associated with pathological and clinical progression, (2) microglia (re)activity and possibly lesion initiation, and (3) loss of lesion activity and scar formation. Our findings highlight that a thorough understanding of the interplay between multiple pathological characteristics is crucial to understand the heterogeneity of MS pathology, as well as its association with genetic predictors and disease outcomes. The scores of donors on the dimensions can serve as an important starting point for further disentanglement of MS heterogeneity and translation into observations and interventions in living cohorts with MS.

Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial.

Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

Influencing factors of home hospice care needs of family caregivers of the older adult with chronic diseases at the end of life in China: a cross-sectional study.

With increased life expectancy in the Chinese population coupled with chronic disease the care needs of people at the end of life are attracting much attention. Home hospice care can help the dying older adult achieve comfort and maintain their dignity at home. However, dying at home means great responsibility and challenge for family caregivers, and there are many unmet needs. The study aimed to investigate the home hospice care needs of family caregivers of older adult people with chronic diseases at the end of life in China, and to analyze the influencing factors of home hospice care needs of caregivers. In this cross-sectional study, from May to September 2023, 4 community health service centers were selected by stratified sampling from seven administrative districts in Jinzhou City, Liaoning Province, where home hospice care was piloted. Then 224 family caregivers were selected from the communities of seven community service centers by simple random sampling method. A general information questionnaire and the home hospice care needs questionnaire developed by our research group were used to investigate. Univariate analysis was used to compare the differences in the scores of different characteristics, and the factors with significant differences were selected for multivariate linear regression analysis to determine the final influencing factors. The total score of hospice care needs of family caregivers was 121.61 ± 15.24, among which the end-of-life knowledge need dimension score was 24.04 ± 2.71, the highest score index was 80.13%, while the symptom control need score was 15.58 ± 3.39, the lowest score index was 62.32%. In addition, Caregivers with caregiving experience, dying older adult with longer disease duration, and dying older adult with higher levels of education were the factors influencing the total need for home hospice care among family caregivers, with a variance explained of 22.7%. The needs of family caregivers of the terminally ill older adult are high, and healthcare professionals should implement services to meet their multidimensional needs and improve the quality of care according to the factors affecting their needs.

Omalizumab withdrawal outcomes in chronic spontaneous urticaria are linked with baseline IgE and eosinophil levels

BackgroundChronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. ObjectiveIn this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. MethodsCSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. ResultsDuring the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered “Oma-responders”, and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. ConclusionOMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.

Physical activity as a mediator in the relationship between health locus of control and health-related quality of life in multiple sclerosis patients with different disease duration

BackgroundThe importance of undertaking physical activity for functioning of patients with multiple sclerosis (MS) has been repeatedly highlighted. However, the research on the role of physical activity in shaping the quality of life of patients with different disease duration is scarce. ObjectiveThe aim of this study was to identify the mediating role of physical activity in the relationship between health locus of control (HLoC) and health-related quality of life in MS patients with varying disease duration. MethodsThe study included 339 patients with MS from rehabilitation centers. The Multiple Sclerosis Impact Scale (MSIS-29) was used to measure health-related quality of life, physical activity was assessed by the Godin Leisure Time Exercise Questionnaire (GLTEQ) and the Health Locus of Control Questionnaire was used to measure HLoC. ResultsPhysical activity has been shown to be a mediator in the relationship between intrinsic HLoC and health-related quality of life particularly in patients with longer disease duration. Intrinsic HLoC was positively associated with engaging in physical activity, which in turn was positively associated with the physical component of quality of life in patients with longer (indirect effect: β = −0.077, p < 0.05) and moderate (β = −0.040, p < 0.05) duration of illness. ConclusionThe results highlight the importance of psychological resources for undertaking quality-of-life-related physical activity by MS patients with long disease duration. Particularly important here is the internal HLoC, which promotes physical activity that increases the chance of a high quality of life.

Evaluation of nail fold capillaroscopy changes in patients with diabetic retinopathy and healthy controls, and its correlation with disease duration, HbA1c levels and severity of diabetic retinopathy: An observational study.

Background Diabetic retinopathy (DR) is an important microvascular complication of long-term type 2 diabetes mellitus (T2DM) leading to blindness if not properly diagnosed and managed. It can develop as early as 7 years before the diagnosis of diabetes. Nail fold capillaroscopy (NFC) is a non-invasive technique for observing capillary microvasculature and there are few studies which have explored the use of NFC in diabetes mellitus patients. Objective To study the nail fold capillaroscopic alterations in patients with T2DM having diabetic retinopathy and compare them to healthy controls. The secondary objective was to correlate the NFC findings with the duration of diabetes, haemoglobin A1c (HbA1c) levels and the severity of DR. Materials and methods This cross-sectional observational study enrolled 200 patients - 100 cases with T2DM having diabetic retinopathy (as per the American Diabetes Association criteria and Diabetic Retinopathy Disease Severity Scale) and 100 healthy age and sex-matched controls. All patients were subjected to NFC and ophthalmological assessment. Results NFC revealed that patients with DR showed significantly higher frequencies of tortuous, dilated, bushy, meandering, angulated capillaries, avascular areas and micro-haemorrhages as compared to healthy controls (p < 0.05). In proliferative DR (PDR), the frequency of tortuous, bushy capillaries, and avascular areas was statistically high and the capillary density was reduced as compared to non-proliferative DR. The DR patients with longer disease duration (>20) years had a significantly higher frequency of tortuous capillaries, avascular areas, meandering, angulated and dilated capillaries. The frequency of tortuosity, avascular areas, and bushy areas was significantly higher in patients with poor glycaemic control (HbA1c >11). Limitations A larger sample size study with different demographic populations could have provided a broader picture of NFC changes in T2DM patients with DR. Discussion NFC may act as a surrogate marker of retinal involvement in patients with DM and should be performed at regular intervals. Conclusion NFC is a quick, simple, safe, and non-invasive method to assess the capillaroscopic alterations in diabetic patients which inturn can help in assessing the severity of DR.