Abstract
Background
We designed a new multi-modal version of the MSmonitor, called the MSmonitor-Plus and Video calling Care (MPVC), a self-management and education program with e-health ...interventions that combines frequent use of specific questionnaires with video calling in treating multiple sclerosis (MS) patients.
Objective
To assess the effectiveness, cost-effectiveness and feasibility of MPVC compared to care as usual (CAU), with the goal of achieving equal or better quality of life for MS patients and their partners/informal caregivers.
Our hypothesis is that by using MPVC, monitoring will become more efficient, that patients’ self-efficacy, quality of life, and adherence to treatment will improve, and that they will be able to live their lives more autonomously.
Methods
A randomized, parallel-group, open label, non-inferiority trial will be conducted to compare MPVC with CAU in MS patients and their partners/informal caregivers. A total of 208 patients will be included with follow-up measurements for 2 years (at baseline and every 3 months). One hundred four patients will be randomized to MPVC and 104 patients to CAU. Partners/informal caregivers of both groups will be asked to participate.
The study will consist of three parts: 1) a clinical effectiveness study, 2) an economic evaluation, and 3) a process evaluation. The primary outcome relates to equal or improved disease-specific physical and mental quality of life of the MS patients. Secondary outcomes relate to self-efficacy, efficiency, cost-effectiveness, autonomy, satisfaction with the care provided, and quality of life of partners/informal caregivers.
Discussion
The idea behind using MPVC is that MS patients will gain more insight into the individual course of the disease and get a better grip on their symptoms. This knowledge should increase their autonomy, give patients more control of their condition and enable them to better and proactively interact with health care professionals.
As the consulting process becomes more efficient with the use of MPVC, MS-related problems could be detected earlier, enabling earlier multidisciplinary care, treatment or modification of the treatment. This could have a positive effect on the quality of life for both the MS patient and his/her partner/informal caregiver, reducing health and social costs.
Trial registration
NCT05242731 Clinical Trials.gov. Date of registration: 16 February 2022 retrospectively registered.
Multiple sclerosis (MS) is a degenerative disease of the central nervous system in which auto-immunity-induced demyelination occurs. MS is thought to be caused by a complex interplay of environmental ...and genetic risk factors. While most genetic studies have focused on identifying common genetic variants for MS through genome-wide association studies, the objective of the present study was to identify rare genetic variants contributing to MS susceptibility. We used whole exome sequencing (WES) followed by co-segregation analyses in nine multi-incident families with two to four affected individuals. WES was performed in 31 family members with and without MS. After applying a suite of selection criteria, co-segregation analyses for a number of rare variants selected from the WES results were performed, adding 24 family members. This approach resulted in 12 exonic rare variants that showed acceptable co-segregation with MS within the nine families, implicating the genes MBP, PLK1, MECP2, MTMR7, TOX3, CPT1A, SORCS1, TRIM66, ITPR3, TTC28, CACNA1F, and PRAM1. Of these, three genes (MBP, MECP2, and CPT1A) have been previously reported as carrying MS-related rare variants. Six additional genes (MTMR7, TOX3, SORCS1, ITPR3, TTC28, and PRAM1) have also been implicated in MS through common genetic variants. The proteins encoded by all twelve genes containing rare variants interact in a molecular framework that points to biological processes involved in (de-/re-)myelination and auto-immunity. Our approach provides clues to possible molecular mechanisms underlying MS that should be studied further in cellular and/or animal models.
Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval ...dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.
Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated.
255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms.
Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.
•Many natalizumab treated MS patients experience wearing-off symptoms.•Extension of natalizumab treatment intervals does not increase wearing-off symptoms.•Wearing-off symptoms are not related to natalizumab drug concentrations.
To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA.
347 ...participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n = 260; +0.1 ± 4.0 kg, +0.2 ± 4.4%), weight gain (n = 43; +8.6 ± 4.0 kg, +9.8 ± 4.1%) or weight loss (n = 44; −9.0 ± 7.2 kg, −9.8 ± 7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations.
687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2 kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39–5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92–2.84) and 53% (OR 1.53; 95%CI 0.92–2.56) in the weight gain vs the stable weight subgroup.
In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.
To determine the incidence and prevalence of hip osteoarthritis (OA) in electronic health records (EHRs) of Dutch general practices by using narrative and codified data.
A retrospective cohort study ...was conducted using the Integrated Primary Care Information database. An algorithm was developed to identify patients with narratively diagnosed hip OA in addition to patients with codified hip OA. Incidence and prevalence estimates among people aged ≥30 were assessed from 2008 to 2019. The association of comorbidities with codified hip OA diagnosis was analysed using multivariable logistic regression.
Using the hip OA narrative data algorithm (positive predicted value = 72%) in addition to codified hip OA showed a prevalence of 1.76–1.95 times higher and increased from 4.03% in 2008 to 7.34% in 2019. The incidence was 1.83–2.41 times higher and increased from 6.83 to 7.78 per 1000 person-years from 2008 to 2019. Among codified hip OA patients, 39.4% had a previous record of narratively diagnosed hip OA, on average approximately 1.93 years earlier. Hip OA patients with a previous record of spinal OA, knee OA, hypertension, and hyperlipidaemia were more likely to be recorded with a hip OA code.
This study using Dutch EHRs showed that epidemiological estimates of hip OA are likely to be an underestimation. Using our algorithm, narrative data can be added to codified data for more realistic epidemiological estimates based on routine healthcare data. However, developing a valid algorithm remains a challenge, possibly due to the diagnostic complexity of hip pain in general practice.
Ankle osteoarthritis(OA) has detrimental effects on physical health and has a relatively early disease onset compared to OA in other joints. However, the prevalence of radiographic ankle OA in ...different subgroups of patients referred for ankle radiography remains unknown. Therefore, we aimed to determine the prevalence of radiographic talocrural, subtalar and talonavicular OA(Kellgren-Lawrence scale ≥2) in a population referred for ankle radiography. Moreover, we aimed to identify differences in prevalence between specific subgroups of patients i.e. Body Mass Index (BMI), sex, age and reason for referral.
A cross-sectional study was conducted at a radiology department serving primary and secondary care. Patients completed a questionnaire before radiography. Features of radiographic ankle OA were assessed for subgroups of patients, including; BMI, sex, age and reason for referral (chronic vs (sub)acute complaints). To examine the difference in (features of) radiographic OA for subgroups, multinomial and logistic regression were used to calculate Odds Ratios (ORs), with adjustment for age, sex and BMI.
Data from 893 patients that visited the radiology department across 16 months in 2017 or 2018 were included for analysis. Prevalence of radiographic ankle OA was 9.2%, 0.4% and 7.0%, for the talocrural, subtalar and talonavicular joint, respectively. Obesity was associated with radiographic talonavicular OA (adjusted OR 2.16, 95%CI:1.09; 5.26). Radiographic talocrural and talonavicular OA were both positively associated with male sex (adjusted OR 4.64, 95%CI:276; 7.81) and (adjusted OR 1.95, 95%CI:1.13; 3.35), respectively.
Radiographic ankle OA was more common in men and obese patients that were referred to radiology.
To assess the associations of biomarkers in serum highsensitivity C-reactive protein (hs-CRP), serum cartilage oligomeric protein (sCOMP), serum propeptide of type I procollagen (sPINP) and serum ...osteocalcin (sOC) and urine urinary type II collagen telopeptide (uCTX-2) with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA).
hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1,002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses.
hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95% CI 1.01–1.37), with mild and moderate pain while walking (OR 1.17 95% CI 1.01–1.35 and OR 1.56 95% CI 1.29–1.90, respectively) and with progression of nocturnal pain (OR 1.25 95% CI 1.07–1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95% CI 1.05–1.85) and with mild and severe-extreme pain while walking (OR 1.35 95% CI 1.04–1.75 and OR 2.55 95% CI 1.03–6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95% CI 0.25–0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue.
This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.
To determine patients', healthcare providers', and insurance company employees' preferences for knee and hip osteoarthritis (KHOA) care.
In a discrete choice experiment, patients with KHOA or a joint ...replacement, healthcare providers, and insurance company employees were repetitively asked to choose between KHOA care alternatives that differed in six attributes: waiting times, out of pocket costs, travel distance, involved healthcare providers, duration of consultation, and access to specialist equipment. A (panel latent class) conditional logit model was used to determine preference heterogeneity and relative importance of the attributes.
Patients (n = 648) and healthcare providers (n = 76) valued low out of pocket costs most, while insurance company employees (n = 150) found a joint consultation by general practitioner (GP) and orthopaedist most important. Patients found the duration of consultation less important than healthcare providers and insurance company employees did. Patients without a joint replacement were likely to prefer healthcare with low out of pocket costs. Patients with a joint replacement and/or low disease-specific quality of life were likely to prefer healthcare from an orthopaedist. Patients who already received healthcare for knee/hip problems were likely to prefer a joint consultation by GP and orthopaedist, and direct access to specialist equipment.
Patients, healthcare providers, and insurance company employees highly prefer a joint consultation by GP and orthopaedist with low out of pocket costs. Within patients, there is substantial preference heterogeneity. These results can be used by policy makers and healthcare providers to choose the most optimal combination of KHOA care aligned to patients' preferences.
Ankle symptoms are a common reason to consult the general practitioner and often persist for years. In a population referred for ankle radiography, the prevalence of radiographic osteoarthritis (OA) ...is substantial, but its additional predictive value for persistent symptoms is unknown. Therefore, we examined the prognosis of symptoms 2–3 years after referral for ankle radiography, assessed clinical prognostic factors, and the additional predictive value of radiographic OA for persistent ankle complaints.
We included 893 adults referred for ankle radiography and studied the following candidate prognostic factors at baseline: age, sex, body mass index (BMI), referral for chronic complaints (>3 months), pain during activity (NRS-11) and presence of stiffness and functional loss as predominant symptom. X-rays were scored for radiographic OA. After 2–3 years participants were invited for a follow-up questionnaire including persistence of ankle complaints. To assess prognostic factors for persistent complaints, uni- and multivariable logistic regression were used.
Of the 194 responders at follow-up, ankle complaints persisted in 71(36.6 %). BMI (OR 1.08; 95 % CI 1.01–1.15), stiffness as predominant symptom (OR 1.69; 95 % CI 0.89–3.21), and chronic complaints (OR 2.84; 95 % CI 1.45–5.57) were in the initial model for persistent complaints (AUC=0.69). After adding radiographic OA (OR 2.36; 95 % CI 1.01–5.50), the AUC of the final model became 0.70.
Ankle complaints persist in a considerable proportion of patients 2–3 years after referral for ankle radiography. BMI, chronic complaints and radiographic OA are prognostic factors for persistent complaints, but the additional predictive value of radiographic OA on top of clinical factors is negligible.
Summary Objective To evaluate the preventive effects of a randomized controlled trial on progression of Magnetic Resonance Imaging (MRI) features of knee osteoarthritis (OA) in overweight and obese ...women. Design In a 2 × 2 factorial design, 2.5 years effects of a diet and exercise program and of glucosamine sulphate (double-blind, placebo-controlled) were evaluated in 407 middle-aged women with body mass index (BMI) ≥ 27 kg/m2 without clinical signs of knee OA at baseline (ISRCTN 42823086). MRIs were scored with the MRI Osteoarthritis Knee Score (MOAKS). Progression was defined for bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities and meniscal extrusion. Analyses on knee level were performed over the four intervention groups using adjusted Generalized Estimating Equations (GEE). Results 687 knees of 347 women with mean age 55.7 years (±3.2 SD) and mean BMI 32.3 kg/m2 (±4.2 SD) were analyzed. Baseline prevalence was 64% for BMLs, 70% for cartilage defects, 24% for osteophytes, 66% for meniscal abnormalities and 52% for meniscal extrusions. The diet and exercise program + placebo intervention showed significantly less progression of meniscal extrusion compared to placebo only (12% vs 22%, OR 0.50, 95% CI 0.27–0.92). The interventions did not result in significant differences on other OA MRI features. Conclusions In subjects at high risk for future knee OA development, a diet and exercise program, glucosamine sulphate and their combination showed small and mainly non-significant effects on the progression of OA MRI features. Only progression of meniscal extrusion was significantly diminished by the diet and exercise program.
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