The ethos brief index-validation of a brief questionnaire to evaluate wellness based on a holistic perspective in patients with restless legs syndrome.

PURPOSE: The aim of this study was to validate the Ethos Brief Index (EBI) in patients with Restless Legs Syndrome (RLS). METHODS: A cross-sectional design, including 788 subjects with RLS (65% women, 70.8 years, SD 11.3) from the Swedish RLS Association, was used. A postal survey was sent out to collect data regarding socio demographics, comorbidities, and RLS-related treatment data. Questionnaires included were EBI, the Restless Legs Syndrome-6 Scale (RLS-6), Restless Legs Syndrome-Quality of Life questionnaire (RLSQoL), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). The validity and reliability of the EBI were investigated using Rasch and confirmatory factor analysis (CFA) models. Measurement invariance, unidimensionality, and differential item functioning (DIF) across age and gender groups, as well as insomnia, daytime sleepiness, RLS-related QoL and RLS severity were assessed. RESULTS: The results supported the unidimensionality of the EBI in the CFA (i.e., explaining 61.5% of the variance) and the Rasch model. The reliability of the EBI was confirmed using composite reliability and Cronbach's alpha. No DIF was identified for gender, age, insomnia, daytime sleepiness, RLS severity or RLS-related QoL. CONCLUSION: The EBI showed good validity and reliability and operated equivalently for male and female patients with RLS. Accordingly, healthcare professionals can use the EBI as a psychometrically sound tool to explore and identify patient-centered problems related to the whole life situation.

Experiences of facilitators and barriers for fulfilment of human needs when living with restless legs syndrome: a qualitative study.

PURPOSE: Restless Legs Syndrome (RLS) is a widespread condition that affects sleep leading to daytime sleepiness, depression, and reduced quality of life. This study aims to determine and describe how patients with RLS experience their everyday life, with a focus on facilitators and barriers related to Maslow's hierarchical theory of human needs. METHOD: Semi-structured interviews were analysed with qualitative content analysis resulting in facilitators and barriers affecting the fulfilment of the five human needs. RESULTS: Addressing RLS symptoms through medications and a quiet sleep environment fulfils psychological needs. Control over RLS symptoms, engagement in activities, trust in treatments, and social support meet safety and security needs. Social inclusion, close relationships, and meaningful interactions fulfil a sense of belongingness and love needs despite RLS. Competence in managing RLS, effective self-care strategies, confident communication, and trust-building support esteem needs. Finally, comprehensive understanding through person-centred interventions and coping fulfils the self-actualization needs in managing RLS. CONCLUSION: Holistic and person-centred interventions, including facilitators for the fulfilment of physiological, psychological, and social needs could help healthcare professionals to provide holistic care.

Quality of life among patients with restless legs syndrome: A systematic review and meta-analysis.

OBJECTIVE: The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS). Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables. METHODS: Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318). RESULTS: Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0-100, i.e., low-high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0-100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0-100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of -0.78, -0.57 and -0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women. CONCLUSION: Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.

Validation of two brief instruments (the SURE and CollaboRATE) to measure shared decision-making in patients with restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological disorder characterised by an urge to move arms and legs, usually associated with discomfort, pain, motor restlessness, and sleep disturbance. An individually adapted treatment is needed but difficult to optimise, which makes shared decision-making (SDM) important. However, brief validated instruments on how patients with RLS perceive their involvement in treatment decisions are lacking. Therefore, the aim was to validate two instruments, SURE (Sure of myself, Understand information, Risk-benefit ratio, Encouragement, i.e., to assess decisional conflict) and CollaboRATE (brief patient survey focused on SDM, i.e., to assess SDM), in patients with RLS. A cross-sectional design, including 788 participants with RLS (65% females, mean [SD] age 70.8 [11.4] years) from a national patient organisation for RLS, was used. A postal survey was sent out to collect data regarding weight, height, comorbidities, demographics, and RLS-related treatment data. The following instruments were included: the SURE, CollaboRATE, Restless Legs Syndrome-6 Scale, and eHealth Literacy Scale. Confirmatory factor analysis and Rasch models were used to assess the validity and reliability of the SURE and CollaboRATE. Measurement invariance, unidimensionality, and differential item functioning (DIF) across age, gender, and medication groups were assessed. The SURE and CollaboRATE were both identified as unidimensional instruments with satisfactory internal consistency. No DIF across age and gender was identified, while significant DIF was observed for both the SURE and CollaboRATE regarding medication use categories. However, both the SURE and CollaboRATE are potential instruments to be used in research, but also as reflection tools by healthcare professionals, patients, and students to explore and assess SDM, and support its development in clinical care.

Lived experience of persons with multiple sclerosis: A qualitative interview study.

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disease with a substantial impact on quality of life and functional capability. The prognosis of MS has changed over time due to the development of increasingly effective therapies. As the knowledge and perceptions of persons living with chronic conditions increasingly have been acknowledged, it has become important to understand lived experiences with a focus on everyday events and experiences as a way of knowing and interpreting the world. Exploring context-specific lived experiences as a source of knowledge about the disease and care may contribute to more precision in designing care services. The aim of this study was to explore the lived experience of persons living with MS in a Swedish context. MATERIALS AND METHODS: A qualitative interview study was conducted with both purposeful and random sampling strategies, resulting in 10 interviews. Data were analyzed using inductive thematic content analysis. RESULTS: The analysis generated 4 overarching themes with 12 subthemes, the 4 themes were: perspectives on life and health, influence on everyday life, relations with healthcare, and shared healthcare processes. The themes are concerned with the patients' own perspectives and context as well as medical and healthcare-related perspectives. Patterns of shared experiences were found, for example, in the diagnosis confirmation, future perspectives, and planning and coordination. More diverse experiences appeared concerning relations with others, one's individual requirements, symptoms and consequences, and knowledge building. CONCLUSION: The findings suggest a need for a more diverse and coproduced development of healthcare services to meet diverse needs in the population with greater acknowledgement of the person's lived experience, including consideration of the complexity of the disease, personal integrity, and different ways of knowing. Findings from this study will be further explored together with other quantitative and qualitative data.

Worldwide estimation of restless legs syndrome: a systematic review and meta-analysis of prevalence in the general adult population.

This systematic review, meta-analysis and meta-regression assessed the prevalence of restless legs syndrome (RLS) in the general adult population. Studies identified in Scopus, PubMed, Web of Science, and PsycInfo between January 2000 and February 2022 were included if they used a case-control or cross-sectional design and reported data regarding the prevalence of RLS. The protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022300709). A total of 97 studies including 483,079 participants from 33 different countries met the eligibility criteria. The Newcastle Ottawa Scale was used to evaluate the methodological quality, and the fill-and-trim method was used to correct probable publication bias, while the jack-knife method was performed to assess small study effect. The corrected overall pooled prevalence of RLS was 3% (95% confidence interval [CI] 1.4%-3.8%). The pooled prevalence of RLS syndrome was affected by methodological quality (no data from non-respondents in the included studies), gender (higher among women), study design (lower prevalence in case-control versus cohort and cross-sectional studies). The figures for corrected pooled prevalence among men, women, alcohol consumers and smokers were 2.8% (95% CI 2%-3.7%); 4.7% (95% CI 3.2%-6.3%); 1.4% (95% CI 0%-4.2%); and 2.7% (95% CI 0%-5.3%), respectively. The prevalence among male and female participants was lower in community-based versus non-community-based studies. Moreover, the prevalence was higher in developed versus developing countries and among elders versus adults. In conclusion, RLS is a common disorder in the general adult population, with a higher prevalence in women; however, prevalence data are affected by study design and quality.

OCT and VEP correlate to disability in secondary progressive multiple sclerosis.

BACKGROUND: The afferent visual pathway provides a unique opportunity to monitor clinical and subclinical optic neuritis and features of neuroaxonal degeneration in secondary progressive MS. OBJECTIVE: To investigate the usefulness of visual evoked potentials (VEP) and optical coherence tomography (OCT) in evaluating SPMS, and the association between these modalities and clinical course and lesion load on the magnetic resonance imaging (MRI) in patients with SPMS with or without a history of optic neuritis (ON). METHODS: SPMS patients (n = 27) underwent clinical assessment with Expanded Disability Status Scale (EDSS) grading, visual acuity, OCT, and VEP examination. MRI of the brain and spinal cord were evaluated. Ordinal scores of VEP and MRI findings were used in the statistical analyses. RESULTS: The ganglion cell and inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness correlated with VEP latency. VEP P100 score correlated with EDSS. Linear regression showed an association between GCIPL thickness and EDSS as well as VEP P100 latency and EDSS. The MRI analyses were negative. CONCLUSION: VEP latency and GCIPL thickness correlated with disability measured as EDSS in patients with SPMS and are useful in monitoring SPMS patients.

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3rd trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved. In this study, we used the highly sensitive and specific proximity extension assay technology to perform protein profiling analysis of 92 inflammation-related proteins in MS patients (n=15) and healthy controls (n=10), longitudinally sampled before, during, and after pregnancy. Differential expression analysis was performed using linear models and p-values were adjusted for false discovery rate due to multiple comparisons. Our findings reveal gradual dynamic changes in plasma proteins that are most prominent during the 3rd trimester while reverting post-partum. Thus, this pattern reflects the disease activity of MS during pregnancy. Among the differentially expressed proteins in pregnancy, several proteins with known immunoregulatory properties were upregulated, such as PD-L1, LIF-R, TGF-ß1, and CCL28. On the other hand, inflammatory chemokines such as CCL8, CCL13, and CXCL5, as well as members of the tumor necrosis factor family, TRANCE and TWEAK, were downregulated. Further in-depth studies will reveal if these proteins can serve as biomarkers in MS and whether they are mechanistically involved in the disease amelioration and worsening. A deeper understanding of the mechanisms involved may identify new treatment strategies mimicking the pregnancy milieu.

Contact patterns and costs of multiple sclerosis in the Swedish healthcare system-A population-based quantitative study.

BACKGROUND: The burden of disease for persons with multiple sclerosis (MS) and society is changing due to new treatments. Knowledge about the total need for care is necessary in relation to changing needs and new service models. OBJECTIVE: The aim of this study was to describe the contact patterns for MS patients, calculate costs in health care, and create meaningful subgroups to analyze contact patterns. METHODS: All patients diagnosed with MS at Ryhov Hospital were included. All contacts in the region from January 1, 2018, until September 30, 2019, were retrieved from the hospital administrative system. Data about age, sex, contacts, and diagnosis were registered. The cost was calculated using case costing, and costs for prescriptions were calculated from medical files. RESULTS: During the 21-month period, patients (n = 305) had 9628 contacts and 7471 physical visits, with a total cost of $7,766,109. Seventeen percent of the patients accounted for 48% of the visits. The median annual cost was $7386 in the group with 10 or fewer visits, compared to $22,491 in patients with more than 50 visits. CONCLUSION: There are considerable differences in the utilization of care and cost between patients with MS in an unselected population, meaning that the care needs to be better customized to each patient's demands.

Exploring possible risk factors for time to first fall and 6-month fall incidence in persons with acute stroke.

Objectives: The aim was to explore how the time to the first fall and 6-month fall incidence relates to rapidly and easily collected data in persons with acute stroke. Methods: Out of consecutively admitted patients with stroke at three stroke units, 284 with at least one follow-up were included in this prospective cohort study. During 6 months following discharge, participants reported falls using a diary and monthly phone calls. Data about participants' characteristics, functions, and activities were collected during hospital stay and analyzed in relation to time to first fall by Cox regression and fall incidence by negative binomial regression. Results: Use of ⩾9 medications, paresis in arms, paresis in legs (National Institutes of Health Stroke Scale), impaired protective reactions in sitting (Postural Reactions Test), and limitations in self-care (Barthel Index) were decisive risk factors for time to first fall. Limitations in mobility (Step Test, 30-s Chair Stand Test) were decisive risk factors for high fall incidence (p < 0.0005). Conclusion: Several easily collected participant characteristics, functions, and activities were identified as risk factors for falls. The findings emphasize the width of assessments that can be used for the identification of individuals at risk for falls and that the risk factors vary in different strata of the population. These results are important when developing multivariate risk models. The risk factors differed in part when analyzing the time to the first fall and 6-month fall incidence.

Levels of bioactive endogenous lipids and health-related quality of life in Chronic Idiopathic Axonal Polyneuropathy.

Background: Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain. Methods: Patients (n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA. Results: Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet (80.1 vs. 56.3; P = 0.02). Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons. Conclusion: Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted.

Initial cognitive impairment predicts shorter survival of patients with glioblastoma.

OBJECTIVES: Seizures as presenting symptom of glioblastoma (GBM) are known to predict prolonged survival, whereas the clinical impact of other initial symptoms is less known. Our main objective was to evaluate the influence of different presenting symptoms on survival in a clinical setting. We also assessed lead times, tumour size and localization. METHODS: Medical records of 189 GBM patients were reviewed regarding the first medical appointment, presenting symptom/s, date of diagnostic radiology and survival. Tumour size, localization and treatment data were retrieved. Overall survival was calculated using Kaplan-Meier and Mann-Whitney U test. Cox regression was used for risk estimation. RESULTS: Cognitive impairment as the initial symptom was often misinterpreted in primary health care leading to a delayed diagnosis. Initial global symptoms (66% of all patients) were associated with reduced survival compared to no global symptoms (median 8.4 months vs. 12.6 months). Those with the most common cognitive dysfunctions: change of behaviour, memory impairment and/or disorientation had a reduced median survival to 6.4 months. In contrast, seizures (32%) were associated with longer survival (median 11.2 months vs. 8.3 months). Global symptoms were associated with larger tumours than seizures, but tumour size had no linear association with survival. The setting of the first medical appointment was evenly distributed between primary health care and emergency units. CONCLUSION: Patients with GBM presenting with cognitive symptoms are challenging to identify, have larger tumours and reduced survival. In contrast, epileptic seizures as the first symptom are associated with longer survival and smaller tumours.

Intravenous use of valproic acid in status epilepticus is associated with high risk of hyperammonemia.

PURPOSE: The aim of the study was to examine the frequency of hyperammonemia secondary to valproic acid treatment in status epilepticus and to describe the characteristics of the patients. METHODS: All patients with established status epilepticus during 2014 to 2016 at Ryhov County Hospital were identified in a retrospective case series. Clinical and laboratory findings were collected from electronic medical files and the Metavision database at the intensive care unit (ICU). Hyperammonemia was defined as a concentration of at least 50 µmol/L. RESULTS: 11 of 40 patients developed hyperammonemia. These patients had a significantly longer stay at the ICU (12.6 vs 2.5 days) and at the hospital (22 vs 11 days). All patients with hyperammonemia were treated at the ICU and all received antibiotics. 12 patients were treated with intravenous valproic acid outside the ICU. Hyperammonemia was not related to Body Mass Index, time to initiation of therapy or laboratory abnormalities except anemia (Hemoglobin 104 vs 122 g/l). There was no difference in mortality between groups. CONCLUSION: The risk of hyperammonemia is almost 40% in patients receiving intravenous valproic acid in the ICU setting. The underlying mechanisms are probably either individual susceptibility or high metabolic demands. A high vigilance should be recommended. These data require further research via prospective designs in which multiple variables are controlled to explore the effects of individual factors on treatment outcome.

Improved survival of Swedish glioblastoma patients treated according to Stupp.

OBJECTIVES: The median survival in glioblastoma (GBM) patients used to be less than 1 year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jönköping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. MATERIAL AND METHOD: This study includes all patients from the county of Jönköping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. RESULTS: The mean survival was 110 days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344 days, P < .001) than in the 2006-2012 cohort (mean 220 vs 397 days, P = .02). CONCLUSION: Survival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.

Combined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internet.

Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.

Positive pivot shift after ACL reconstruction predicts later osteoarthrosis: 63 patients followed 5-9 years after surgery.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) may cause osteoarthrosis (OA) and functional impairment. We wanted to find out whether the degree of knee stability obtained after ACL reconstruction correlates with radiographic and clinical outcome. PATIENTS AND METHODS: We examined 63 patients 2 and 5-9 years after anterior cruciate ligament (ACL) reconstruction. Knee stability was assessed 2 years after surgery by recording AP laxity using radiostereometric technique (RSA) and by performing the pivot shift test. Degeneration of the knee joint was evaluated with bone scintigraphy, and radiographically. Functional outcome was assessed with Lysholm score, Tegner activity scale and with the one-leg hop test. RESULTS: Radiographic signs of osteoarthrosis at the most recent follow-up (5-9 years) did not correlate with knee stability. Patients with positive pivot shift test 2 years after surgery showed increased scintigraphic activity of the subchondral bone at the most recent follow-up, and inferior subjective functional outcome 2 years after surgery. Knees having had meniscus resections had more often OA. Radiographical signs of OA were associated with higher scintigraphic uptake in the operated knee relative to the contralateral knee. INTERPRETATION: The ability to obliterate the pivoting by ACL reconstruction appears to be more important than normalizing the AP laxity in order to prevent later OA.