Interventions to support risk and benefit understanding of disease-modifying drugs in Multiple Sclerosis patients:A systematic review

Objective: The present review evaluates interventions that have been designed to improve understanding of the complex risk-benefit profiles of disease-modifying drugs (DMDs) in patients with Multiple Sclerosis (MS). Methods: A systematic search conducted using PubMed, Embase, Google Scholar and PsycINFO identified 15 studies. Interventions which provided treatment information were present across a range of study designs. A narrative synthesis was conducted due to heterogeneity of research findings. Results: Interventions providing treatment information ranged from comprehensive education programmes to booklets of a few pages. MS patients favoured the interventions they received. Understanding of overall treatment information and treatment risks specifically, generally improved following interventions. Yet overestimation of treatment benefits persisted. There was no conclusive effect on DMD decisions. No superior intervention was identified. Conclusion: Interventions designed to improve understanding of DMD risk and benefit information are moderately successful. Practice implications: Additional support provided to MS patients beyond routine healthcare can generally improve understanding of the complex risk-benefit profiles of DMDs. Future interventions need to ensure that patients with symptoms that may confound understanding can also benefit from this additional information.</p

Multiple sclerosis patients' understanding and preferences for risks and benefits of disease-modifying drugs:A systematic review

Background: Multiple sclerosis (MS) patients are faced with complex risk-benefit profiles of disease-modifying drugs (DMDs) when making treatment decisions. For effective shared decision-making, MS patients should understand the risks and benefits of DMDs and make treatment decisions based on personal preferences. Methods: This is an inclusive systematic review to primarily assess current understanding of MS patients for information about DMDs provided during the standard healthcare system.The secondary aim assesses MS patients'preferences for specific risks and benefits of treatments. A systematic search was conducted using PubMed,Embase and Google Scholar. A total of 22 studies were reviewed across both aims. Relevant quantitative and qualitative data was extracted by two authors. A narrative synthesis was conducted due to heterogeneity of research findings. Results: There was a trend for DMD risks to be generally underestimated and DMD benefits to be generally overestimated by MS patients. Treatments that could potentially offer substantial symptom improvement, delay in disease progression, or reduction in relapses were preferred even at the expense of higher risks. Conclusions: Many patients' experience of information during the standard healthcare system does not provide satisfactory understanding of the risks and benefits of DMDs. Effective ways to communicate risk and benefit DMD information when making shared treatment decisions needs to be identified. Patient preferences of DMD risks and benefits should also be taken into accoun

Best Methods of Communicating Clinical Trial Data to Improve Understanding of Treatments for Patients with Multiple Sclerosis

Background Patients’ understanding of treatment risks and benefits is a prerequisite for shared decision making. Yet, patients with multiple sclerosis (MS) do not accurately understand treatment information provided in regular clinical consultations. Objectives To identify the best methods of communicating clinical trial data to improve the understanding of treatments among patients with MS and to also examine the relationship between patients’ understanding with decisional conflict, individual traits, and MS symptoms. Methods A repeated-measures study was used. A sample of relapsing-remitting patients with MS was recruited from National Health Service sites in the United Kingdom. Patients were presented with hypothetical treatment risks and benefits from faux clinical trials. Treatments were communicated using absolute terms, relative terms, and numbers needed to treat/harm. The presence of baseline information with each method was also manipulated. Patients’ understanding and conflict in treatment decisions were assessed. Individual traits and MS symptoms were also recorded. Results Understanding was better when treatments were communicated in absolute terms (mean 3.99 ± 0.93) compared with relative terms (mean 2.93 ± 0.91; P < 0.001) and numbers needed to treat/harm (mean 2.89 ± 0.88; P < 0.001). Adding baseline information to all methods significantly improved understanding (mean 5.04 ± 0.96) compared with no baseline information (mean 1.50 ± 0.74; P < 0.001). Understanding was not related to conflict in treatment decisions (r = −0.131; P = 0.391). Numeracy, IQ, and cognitive impairments were significantly related to patients’ understanding of treatments. Conclusions Treatment risks and benefits should ideally be communicated using absolute terms, alongside baseline information. Patients with MS with low numeracy, low IQ, and reduced cognitive skills should be supported during treatment education

Time-delayed feedback control of unstable periodic orbits near a subcritical Hopf bifurcation

We show that Pyragas delayed feedback control can stabilize an unstable periodic orbit (UPO) that arises from a generic subcritical Hopf bifurcation of a stable equilibrium in an n-dimensional dynamical system. This extends results of Fiedler et al. [PRL 98, 114101 (2007)], who demonstrated that such feedback control can stabilize the UPO associated with a two-dimensional subcritical Hopf normal form. Pyragas feedback requires an appropriate choice of a feedback gain matrix for stabilization, as well as knowledge of the period of the targeted UPO. We apply feedback in the directions tangent to the two-dimensional center manifold. We parameterize the feedback gain by a modulus and a phase angle, and give explicit formulae for choosing these two parameters given the period of the UPO in a neighborhood of the bifurcation point. We show, first heuristically, and then rigorously by a center manifold reduction for delay differential equations, that the stabilization mechanism involves a highly degenerate Hopf bifurcation problem that is induced by the time-delayed feedback. When the feedback gain modulus reaches a threshold for stabilization, both of the genericity assumptions associated with a two-dimensional Hopf bifurcation are violated: the eigenvalues of the linearized problem do not cross the imaginary axis as the bifurcation parameter is varied, and the real part of the cubic coefficient of the normal form vanishes. Our analysis of this degenerate bifurcation problem reveals two qualitatively distinct cases when unfolded in a two-parameter plane. In each case, Pyragas-type feedback successfully stabilizes the branch of small-amplitude UPOs in a neighborhood of the original bifurcation point, provided that the phase angle satisfies a certain restriction.Comment: 35 pages, 19 figure

EAN Guideline on Palliative Care of People with Severe, Progressive Multiple Sclerosis

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients–Intervention– Comparator–Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient’s wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs

How integrated are neurology and palliative care services? Results of a multicentre mapping exercise

Background: Patients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services interact. This study aimed to map the current level of connections and integration between these services. Methods: The mapping exercise was conducted in eight centres with neurology and palliative care services in the United Kingdom. The data were provided by the respective neurology and specialist palliative care teams. Questions focused on: i) catchment and population served; ii) service provision and staffing; iii) integration and relationships. Results: Centres varied in size of catchment areas (39-5,840 square miles) and population served (142,000-3,500,000). Neurology and specialist palliative care were often not co-terminus. Service provisions for neurology and specialist palliative care were also varied. For example, neurology services varied in the number and type of provided clinics and palliative care services in the settings they work in. Integration was most developed in Motor Neuron Disease (MND), e.g., joint meetings were often held, followed by Parkinsonism (made up of Parkinson’s Disease (PD), Multiple-System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP), with integration being more developed for MSA and PSP) and least in Multiple Sclerosis (MS), e.g., most sites had no formal links. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (range: 9–88 MND, 3–25 Parkinsonism, and 0–5 MS). Conclusions: This mapping exercise showed heterogeneity in service provision and integration between neurology and specialist palliative care services, which varied not only between sites but also between diseases. This highlights the need and opportunities for improved models of integration, which should be rigorously tested for effectiveness

Immediate versus delayed short-term integrated palliative care for advanced long-term neurological conditions: the OPTCARE Neuro RCT

BackgroundPalliative care is recommended to help meet the needs of patients with progressive non-cancer conditions, such as long-term neurological conditions. However, few trials have tested palliative care in this population.ObjectivesTo determine the effectiveness and cost-effectiveness of short-term integrated palliative care in improving symptoms, improving patient- and caregiver-reported outcomes and reducing hospital use for people severely affected by long-term neurological conditions.DesignPragmatic, randomised controlled, multicentre, fast-track trial, with an embedded qualitative component and surveys.SettingSeven UK centres (South London, Nottingham, Liverpool, Cardiff, Brighton, Ashford and Sheffield) with multiprofessional palliative care teams and neurology services.ParticipantsPeople living with multiple sclerosis, idiopathic Parkinson’s disease, motor neurone disease, multiple system atrophy or progressive supranuclear palsy, with unresolved symptoms and/or complex psychosocial needs. The qualitative study involved patients, caregivers and health-care staff.InterventionsParticipants were randomised to receive short-term integrated palliative care, delivered by multiprofessional teams, immediately or after a 12-week wait (standard care group).Main outcome measuresThe primary outcome was a combined score of eight symptoms measured by the Integrated Palliative care Outcome Scale for Neurological conditions 8 symptom subscale (IPOS Neuro-S8) at 12 weeks. Secondary outcomes included patients’ other physical and psychological symptoms, quality of life (EuroQol-5 Dimensions, five-level version), care satisfaction, caregiver burden, service use and cost, and harms. Data were analysed using multiple imputation, generalised linear mixed models, incremental cost-effectiveness ratios (threshold was the National Institute for Health and Care Excellence £20,000 per quality-adjusted life-year) and cost-effectiveness planes. Qualitative data were analysed thematically.ResultsWe recruited 350 patients and 229 caregivers. There were no significant between-group differences for primary or secondary outcomes. Patients receiving short-term integrated palliative care had a significant improvement, from baseline to 12 weeks, on the primary outcome IPOS Neuro-S8 (–0.78, 95% confidence interval –1.29 to –0.26) and the secondary outcome of 24 physical symptoms (–1.95, 99.55% confidence interval –3.60 to –0.30). This was not seen in the control group, in which conversely, care satisfaction significantly reduced from baseline to 12 weeks (–2.89, 99.55% confidence interval –5.19 to –0.59). Incremental cost-effectiveness ratios were smaller than the set threshold (EuroQol-5 Dimensions index score –£23,545; IPOS Neuro-S8 –£1519), indicating that the intervention provided cost savings plus better outcomes. Deaths, survival and hospitalisations were similar between the two groups. Qualitative data suggested that the impact of the intervention encompassed three themes: (1) adapting to losses and building resilience, (2) attending to function, deficits and maintaining stability, and (3) enabling caregivers to care.ConclusionsOur results indicate that short-term integrated palliative care provides improvements in patient-reported physical symptoms at a lower cost and without harmful effects when compared with standard care.LimitationsOutcome measures may not have been sensitive enough to capture the multidimensional changes from the intervention. Our surveys found that the control/standard and intervention services were heterogeneous.Future workRefining short-term integrated palliative care and similar approaches for long-term neurological conditions, focusing on better integration of existing services, criteria for referral and research to improve symptom management