Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

Heterogeneous microgeographic genetic structure of the common cockle (Cerastoderma edule) in the Northeast Atlantic Ocean: biogeographic barriers and environmental factors.

Knowledge of genetic structure at the finest level is essential for the conservation of genetic resources. Despite no visible barriers limiting gene flow, significant genetic structure has been shown in marine species. The common cockle (Cerastoderma edule) is a bivalve of great commercial and ecological value inhabiting the Northeast Atlantic Ocean. Previous population genomics studies demonstrated significant structure both across the Northeast Atlantic, but also within small geographic areas, highlighting the need to investigate fine-scale structuring. Here, we analysed two geographic areas that could represent opposite models of structure for the species: (1) the SW British Isles region, highly fragmented due to biogeographic barriers, and (2) Galicia (NW Spain), a putative homogeneous region. A total of 9250 SNPs genotyped by 2b-RAD on 599 individuals from 22 natural beds were used for the analysis. The entire SNP dataset mostly confirmed previous observations related to genetic diversity and differentiation; however, neutral and divergent SNP outlier datasets enabled disentangling physical barriers from abiotic environmental factors structuring both regions. While Galicia showed a homogeneous structure, the SW British Isles region was split into four reliable genetic regions related to oceanographic features and abiotic factors, such as sea surface salinity and temperature. The information gathered supports specific management policies of cockle resources in SW British and Galician regions also considering their particular socio-economic characteristics; further, these new data will be added to those recently reported in the Northeast Atlantic to define sustainable management actions across the whole distribution range of the species.

Frailty and Falls in People Living With Multiple Sclerosis.

OBJECTIVE: To explore the association between frailty and history of falls in people living with multiple sclerosis (MS). DESIGN: Secondary analysis. SETTING: University research laboratories in the United States and Israel. PARTICIPANTS: A total of 118 people (N=118) with relapsing-remitting MS (mean age, 48.9±10.0 years; 74.6% female; Expanded Disability Status Scale [EDSS] range, 1.0-6.0) were studied in this cross-sectional analysis. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A frailty index was calculated from 40 health deficits by following standard validated procedures. The number of falls (12-month history) was recorded. RESULTS: Overall, 33.9%, 29.7%, and 36.4% of participants were classified as nonfrail, moderately frail, and severely frail, respectively. The frailty index was significantly correlated (ρ=0.37, P<.001) with higher scores on the EDSS. In univariable negative binomial regression analysis, the frailty index was associated with a higher number of falls (incidence rate ratio [IRR]=3.33; 95% CI, 1.85-5.99; P<.001). After adjustment for age, sex, and EDSS, frailty remained strongly associated with history of falls (IRR=2.78; 95% CI, 1.51-5.10; P=.001). CONCLUSIONS: The current study identifies a significant relationship between frailty and history of falls in MS, independent of age, sex, and disease severity. These findings support the notion that frailty is a syndrome related to but independent of disability in MS.

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis.

BACKGROUND: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis. METHODS: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis. RESULTS: Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression. CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).

Co-occurrence of pathogen assemblages in a keystone species the common cockle Cerastoderma edule on the Irish coast.

Despite coinfections being recognized as the rule in animal populations, most studies focus on single pathogen systems. Pathogen interaction networks and the drivers of such associations are lacking in disease ecology studies. Common cockle Cerastoderma edule populations are exposed to a great diversity of pathogens, thus making them a good model system to investigate. This study examined the diversity and prevalence of pathogens from different taxonomic levels in wild and fished C. edule on the Irish coast. Potential interactions were tested focussing on abiotic (seawater temperature and salinity) and biotic (cockle size and age, and epiflora on shells) factors. No Microsporidia nor OsHV-1µVar were detected. Single infections with Haplosporidia (37.7%) or Vibrio (25.3%) were more common than two-pathogen coinfected individuals (9.5%), which may more easily succumb to infection. Fished C. edule populations with high cockle densities were more exposed to infections. Higher temperature and presence of epiflora on cockle shells promoted coinfection in warmer months. Low seawater salinity, host condition and proximity to other infected host species influenced coinfection distribution. A positive association between two Minchinia spp. was observed, most likely due to their different pathogenic effect. Findings highlight the major influence that ecological factors have on pathogen interactions and host­pathogen interplay.

What do the terms resistance, tolerance, and resilience mean in the case of Ostrea edulis infected by the haplosporidian parasite Bonamia ostreae.

The decline of the European flat oyster Ostrea edulis represents a loss to European coastal economies both in terms of food security and by affecting the Good Environmental Status of the marine environment as set out by the European Council's Marine Strategy Framework Directive (2008/56/EC). Restoration of O. edulis habitat is being widely discussed across Europe, addressing key challenges such as the devastating impact of the haplosporidian parasite Bonamia ostreae. The use of resistant, tolerant, or resilient oysters as restoration broodstock has been proposed by restoration practitioners, but the definitions and implications of these superficially familiar terms have yet to be defined and agreed by all stakeholders. This opinion piece considers the challenges of differentiating Bonamia resistance, tolerance, and resilience; challenges which impede the adoption of robust definitions. We argue that, disease-resistance is reduced susceptibility to infection by the parasite, or active suppression of the parasites ability to multiply and proliferate. Disease-tolerance is the retention of fitness and an ability to neutralise the virulence of the parasite. Disease-resilience is the ability to recover from illness and, at population level, tolerance could be interpreted as resilience. We concede that further work is required to resolve practical uncertainty in applying these definitions, and argue for a collaboration of experts to achieve consensus. Failure to act now might result in the future dispersal of this disease into new locations and populations, because robust definitions are important components of regulatory mechanisms that underpin marine management.

Polypharmacy in Multiple Sclerosis: Current Knowledge and Future Directions.

Polypharmacy, or the daily use of five or more medications, is well documented in older adults and linked to negative outcomes such as medication errors, adverse drug reactions, and increased healthcare utilization. Like older adults, people with multiple sclerosis (PwMS) are susceptible to polypharmacy, owing to the variety of treatments used to address individual multiple sclerosis (MS) symptoms and other comorbidities. Between 15-65% of PwMS meet criteria for polypharmacy; in this population, polypharmacy is associated with increased reports of fatigue, subjective cognitive impairment, and reduced quality of life. Despite evidence of adverse outcomes, polypharmacy among PwMS remains a neglected area of research. This article examines the current literature regarding polypharmacy in MS, as well as implications for clinical practice and directions for future research.

Discontinuing Treatment Against Medical Advice: The Role of Perceived Autonomy Support From Providers in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Long-term medication adherence is problematic among patients with chronic medical conditions. To our knowledge, this was the first study to examine factors associated with nonadherence among patients with relapsing-remitting multiple sclerosis who discontinue disease-modifying treatments against medical advice. PURPOSE: To examine differences in perceived provider autonomy support between disease-modifying treatment-adherent relapsing-remitting multiple sclerosis patients and relapsing-remitting multiple sclerosis patients who discontinued disease-modifying treatments against medical advice. METHODS: Self-report questionnaires and a neurologic exam were administered to demographically matched adherent (n = 50) and nonadherent (n = 79) relapsing- remitting multiple sclerosis patients from the Midwest and Northeast USA. RESULTS: Adherent patients reported greater perceived autonomy support from their treatment providers, F(1, 124) = 28.170, p < .001, partial η2 = .185. This difference persisted after controlling for current multiple sclerosis healthcare provider, education, disease duration, Expanded Disability Status Scale, perceived barriers to adherence, and prevalence of side effects, F(1, 121) = 9.61, p = .002, partial η2 = .074. Neither depressive symptoms, F(1, 124) = 1.001, p > .05, partial η2 = .009, nor the occurrence of a major depressive episode, χ2(1, N = 129) = .288, p > .05, differed between adherent and nonadherent patients. CONCLUSIONS: Greater perceived autonomy support from treatment providers may increase adherence to disease-modifying treatments among patients who discontinue treatment against medical advice. Results may inform interventions for patients who discontinue treatment against medical advice.

Reasons for nonadherence and response to treatment in an adherence intervention trial for relapsing-remitting multiple sclerosis patients.

OBJECTIVES: To explore whether patients in an adherence trial who appeared not to take disease modifying therapy (DMT) for avoidance reasons could be reliably identified, by observational coding, for their main reason of not taking DMT. To determine whether reason groups could be distinguished by clinical and self-report psychological characteristics and intervention outcomes. METHOD: Participants were multiple sclerosis patients (N = 78, 88.5% female, mean age 45.64) demotivated to take DMT. Audio recordings of the sessions were coded for the main reason of not taking DMT. Reason groups were compared based on patient characteristics and intervention outcomes. RESULTS: Avoidance and three other reasons for not taking DMT (side effects, cost, and mild course) were reliably identified (κ = 0.88). Patient characteristics failed to distinguish participants in the Avoidance group, which also had poorer outcomes (X2 [2, n = 73] = 6.35, p = 0.036). CONCLUSIONS: Patients not taking DMT for avoidance reasons may need novel methods to identify them and encourage (re-)initiation.

Improved cognitive outcomes in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta: Results from the DECIDE study.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain. OBJECTIVE: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT). METHODS: In DECIDE, patients with relapsing-remitting multiple sclerosis (RRMS) (age: 18-55 years; Expanded Disability Status Scale (EDSS) score 0-5.0) were randomized to daclizumab beta ( n = 919) or IM IFN beta-1a ( n = 922) for 96-144 weeks. SDMT was administered at baseline and at 24-week intervals. RESULTS: At week 96, significantly greater mean improvement from baseline in SDMT was observed with daclizumab beta versus IM IFN beta-1a ( p = 0.0274). Significantly more patients treated with daclizumab beta showed clinically meaningful improvement in SDMT (increase from baseline of ⩾3 points ( p = 0.0153) or ⩾4 points ( p = 0.0366)), and significantly fewer patients showed clinically meaningful worsening (decrease from baseline of ⩾3 points ( p = 0.0103)). Odds representing risk of worsening versus stability or improvement on SDMT were significantly smaller for daclizumab beta ( p = 0.0088 (3-point threshold); p = 0.0267 (4-point threshold)). In patients completing 144 weeks of treatment, the effects of daclizumab beta were generally sustained. CONCLUSION: These results provide evidence for a benefit of daclizumab beta versus IM IFN beta-1a on cognitive processing speed in RRMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01064401 (Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon ß 1a in Participants With Relapsing-Remitting Multiple Sclerosis (DECIDE)): https://clinicaltrials.gov/ct2/show/NCT01064401 .

In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis.

BACKGROUND: The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). OBJECTIVE: We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. METHODS: GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). RESULTS: Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. CONCLUSION: Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.

Assessment of the effects of sulfated polysaccharides extracted from the red seaweed Irish moss Chondrus crispus on the immune-stimulant activity in mussels Mytilus spp.

Seaweeds contain a number of health enhancing and antimicrobial bioactive compounds including sulfated polysaccharides (SP). In the present study, SP extracted from a European red seaweed Irish moss Chondrus crispus was chemically analyzed, SP content extracted and the immune-response effect on wild Irish mussels Mytilus spp. investigated for the first time. A high percent yield of SP was extracted from C. crispus and the immune-stimulant activity of SP was assessed in a laboratory trial with mussels exposed to three different treatments of low (10 µg mL-1), medium (20 µg mL-1) and high (50 µg mL-1) SP dose concentrations and a control mussel group with no exposure to SP. An initial mussel sample was processed prior to the trial commencing and mussels were subsequently sampled on Days 1, 2, 3, 4, 7, and 10 post SP exposure. Both cell, humoral and immune related gene responses including haemocyte cell viability, haemocyte counts, lysozyme activity and expression of immune related genes (defensin, mytimycin and lysozyme mRNA) were assessed. No mussel mortalities were observed in either the treated or non-treated groups. Mussels exposed with SP showed an increase in haemocyte cell viability and the total number of haemocytes compared to control mussels. Lysozyme activity was also higher in treated mussels. Additionally, up-regulated expression of defensin, mytimycin and lysozyme mRNA was observed in SP treated mussels shortly after exposure (on Days 1, 2, and 3) to SP. These results indicate that a high quality yield of SP can be readily extracted from C. crispus and more importantly based on the animal model used in this study, SP extracted from C. crispus can rapidly induce health enhancing activities in Mytilus spp. at a cellular, humoral and molecular level and with a prolonged effect up to ten days post treatment.

Dynamic Balance Is Related to Physiological Impairments in Persons With Multiple Sclerosis.

OBJECTIVES: To compare physiological impairments between persons with multiple sclerosis (MS) with a history of falls and persons with MS without a history of falls, and to investigate the association between physiological impairments and dynamic balance. DESIGN: Cross-sectional study. SETTING: University motion analysis laboratory. PARTICIPANTS: Persons with MS (N=55; 27 recurrent fallers and 28 nonfallers). Participants were classified as fallers if they self-reported ≥2 falls in the previous 6 months. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Physiological impairment was assessed with sensorimotor delays, spasticity, plantar cutaneous sensation, and the sensory, cerebellar, and pyramidal subscales of the Expanded Disability Status Scale (EDSS). Dynamic balance was assessed using the average and variability of margin of stability and variability of trunk accelerations. RESULTS: Compared with nonfallers, fallers had lower plantar sensation, longer sensorimotor delays, more spasticity, and more impairment in the pyramidal and cerebellar subscales of the EDSS. Additionally, these impairments were all moderately to strongly correlated with worse dynamic balance. CONCLUSIONS: This study highlights the multifactorial nature of instability in persons with MS. A better understanding of the physiological mechanisms of dynamic instability in persons with MS can be used to improve methods of monitoring disease progression, identifying which impairments to target through interventions, and appropriately evaluating intervention efficacy.

Baseline predictors of DMT reinitiation among patients with multiple sclerosis following an MI-CBT intervention.

Patients with multiple sclerosis (MS) are often nonadherent to their disease modifying therapy (DMT). While recent studies demonstrate enhanced DMT adherence following intervention grounded in motivational interviewing (MI), little is known about how to address DMT reinitiation among MS patients who have prematurely discontinued DMT against medical advice and do not intend to reinitiate. We examined baseline predictors of DMT reinitiation among patients with MS who discontinued medications against medical advice following a telephone-based MI and Cognitive Behavioral Therapy (MI-CBT) intervention. Following MI-CBT intervention, 66 patients reported whether or not they opted to reinitiate DMT. Rate of disease progression (ß = 0.295) and perceived personal control (ß = - 0.131) emerged as unique significant predictors of DMT reinitiation following intervention. Clinical characteristics and health-related beliefs may be used to prospectively identify patients most likely to reinitiate DMT following MI-CBT intervention, furthering the goal of preserving brain health and preventing neurologic decline in MS via appropriate DMT utilization. Further study is warranted to delineate potential mediators and moderators of DMT reinitiation outcomes.

Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis.

BACKGROUND: Increased oxidative stress leads to loss of glutathione (GSH). We have reported lower cerebral GSH in patients with secondary progressive multiple sclerosis (SPMS), indicating the involvement of oxidative stress in multiple sclerosis (MS) pathophysiology. OBJECTIVE: This study expanded upon our earlier work by examining longitudinal changes in cerebral GSH in patients with SPMS in relation to their clinical status. METHODS: A total of 13 patients with SPMS (Expanded Disability Status Scale (EDSS) = 4.0-6.5; MS duration = 21.2 ± 8.7 years) and 12 controls were studied over 3-5 years. GSH mapping was acquired from frontal and parietal regions using a multiple quantum chemical shift imaging technique at 3 T. Clinical assessments of the patient's disability included EDSS, gait, motor strength, ataxia, tremor, brainstem function and vision changes. RESULTS: Brain GSH concentrations in patients were lower than those in controls for both baseline and 3- to 5-year follow-ups. Longitudinal GSH changes of patients were associated with their neurologist's blinded appraisal of their clinical progression. Patients judged to have worsening clinical status had significantly greater declines in frontal GSH concentrations than those with stable clinical status. CONCLUSION: GSH provides a distinct measure associated with the disease progression in SPMS, possibly due to its dynamic alignment with pathogenic processes of MS related to oxidative stress.

Instrumented balance and walking assessments in persons with multiple sclerosis show strong test-retest reliability.

BACKGROUND: There is a need for objective movement assessment for clinical research trials aimed at improving gait and balance in persons with multiple sclerosis (PwMS). Wireless inertial sensors can accurately measure numerous walking and balance parameters but these measures require evaluation of reliability in PwMS. The current study determined the test-retest reliability of wireless inertial sensor measures obtained during an instrumented standing balance test and an instrumented Timed Up and Go test in PwMS. METHODS: Fifteen PwMS and 15 healthy control subjects (HC) performed an instrumented standing balance and instrumented Timed Up and Go (TUG) test on two separate days. Ten instrumented standing balance measures and 18 instrumented TUG measures were computed from the wireless sensor data. Intraclass correlation coefficients (ICC) were calculated to determine test-retest reliability of all instrumented standing balance and instrumented TUG measures. Correlations were evaluated between the instrumented standing balance and instrumented TUG measures and self-reported walking and balance performance, fall history, and clinical disability. RESULTS: For both groups, ICCs for instrumented standing balance measures were best for spatio-temporal measures, while frequency measures were less reliable. All instrumented TUG measures exhibited good to excellent (ICCs > 0.60) test-retest reliability in PwMS and in HC. There were no correlations between self-report walking and balance scores and instrumented TUG or instrumented standing balance metrics, but there were correlations between instrumented TUG and instrumented standing balance metrics and fall history and clinical disability status. CONCLUSIONS: Measures from the instrumented standing balance and instrumented TUG tests exhibit good to excellent reliability, demonstrating their potential as objective assessments for clinical trials. A subset of the most reliable measures is recommended for measuring walking and balance in clinical settings.

Reversible cerebral vasoconstriction syndrome in association with fingolimod use.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within 12 weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS. OBJECTIVE: We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use. METHODS: This is a single observational study without controls; therefore, level of evidence is IV. A literature review in pubmed with keywords, fingolimod, vasospasm, RCVS, Call-Fleming, stroke, PRES and hemorrhage. RESULTS: One case of RCVS on fingolimod in the post-partum period. Two other cases in the literature were found one with hemorrhagic encephalitis and the other critical vasospasm in the upper extremity associated with fingolimod 1.25 mg daily in the FREEDOMS II trial and TRANSFORMS study, respectively. Additionally, Novartis reports nine cases of PRES related to fingolimod use. CONCLUSION: Fingolimod has the potential to cause vasoconstriction however appears to be rare and more likely on doses higher than 0.5 mg daily. Fingolimod may be associated in RCVS and should be considered in patients with severe headache on fingolimod.

Being Kind to Your Future Self: Probability Discounting of Health Decision-Making.

INTRODUCTION: Nearly 50 % of patients with chronic medical illness exhibit poor treatment adherence. When making treatment decisions, these patients must balance the probability of current side effects against the probability of long-term benefits. This study examines if the behavioral economic construct of probability discounting can be used to explain treatment decisions in chronic disease. METHODS: Thirty-eight nonadherent and 39 adherent patients with multiple sclerosis (MS) completed a series of hypothetical treatment scenarios with varied risk and benefit probabilities. RESULTS: As described by a hyperbolic probability discounting model, all patients reported decreased medication initiation as the probability of treatment efficacy decreased and the probability of treatment side effects increased. When compared to adherent patients, nonadherent patients significantly devalued treatment efficacy and inflated treatment risk. DISCUSSION: The methods in this study can be used to identify optimal risk/benefit ratios for treatment development and inform the process by which patients make treatment decisions.

A pilot study to improve adherence among MS patients who discontinue treatment against medical advice.

Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690.