Lifestyle and complementary therapies in multiple sclerosis guidelines: Systematic review

Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle factors such as exercise and smoking cessation. Lifestyle modifications and complementary therapies with proven safety and efficacy are essential as part of best-practice MS management, especially when faced with limited access to healthcare services. However, it is unclear to what extent MS clinical practice guidelines and consensus statements address these strategies. A systematic review was conducted, wherein MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, guideline databases and developer sites were searched for guidelines and consensus statements that addressed lifestyle modifications and complementary therapies of interest. Two researchers independently screened articles, extracted data and assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation version II. Thirty-one guidelines and consensus statements were included. Quality was high for ‘clarity of presentation’ (77%) and ‘scope and purpose’ (73%), moderate for ‘stakeholder development’ (56%), ‘rigour of development’ (48%) and ‘editorial independence’ (47%), and low for ‘applicability’ (29%). Two guidelines, related to physical activity and exercise, mindfulness, smoking cessation, and vitamin D and polyunsaturated fatty acid supplementation, scored high in all domains. These guidelines were two of only four guidelines intended for use by people with MS. High-quality guidelines and consensus statements to guide lifestyle modifications and complementary therapies in MS management are limited. Our findings indicate the need for more guidelines intended for use by people with MS, and a further focus on implementation resources

Physical activity, sitting time and exercise types, and associations with symptoms in Australian people with multiple sclerosis

Purpose Multiple sclerosis (MS) often leads to reduced physical activity and exercise participation. Sedentary behaviour is associated with poor health, whereas exercise is effective in managing MS symptoms. This study assessed physical activity, exercise and sedentary sitting time, and identified associations with symptoms. Material and methods Participants of the Australian MS Longitudinal Study completed surveys in 2016. We measured physical activity and sitting time via the International Physical Activity Questionnaire (short-form), and assessed participation in exercise (type and duration). Multivariable regression models assessed associations between physical activity, sitting time and exercise; and demographic characteristics and MS-related symptoms. Results Of the 1216 participants, 53.0% reported moderate-high physical activity levels (71.5% among those with no/mild disability). Median sitting time was 7 h/day. Most (78.4%) participated in aerobic exercise, while only 16.4% participated in strength training. Having a progressive MS onset, more severe symptoms (i.e., cognitive impairment, depression, fatigue, mobility impairment) and being male was indicative of lower physical activity levels and higher sitting time. Conclusions Health promotion efforts should encourage physical activity and exercise, in particular strength training, among people with MS. People with more severe symptoms and progressive disease may require focused exercise promotion from healthcare professionals

Physical activity participation in Australians with multiple sclerosis: associations with geographical remoteness

Purpose Physical activity (PA) participation offers many benefits for persons with multiple sclerosis (MS). Persons with MS are significantly less active than the general population; however, there is insufficient evidence regarding the association between geographical remoteness and PA participation in persons with MS. We identify PA levels across levels of rurality in an Australian MS population. Materials and methods The Australian MS Longitudinal Study collects regular survey data from persons with MS in Australia, including demographic, clinical, and health behavioural data. Physical activity engagement was identified with the International Physical Activity Questionnaire-short form and geographical remoteness was identified from participants’ postcode using the Access and Remoteness Index for Australia. Hurdle regression analysis examined the relationship between remoteness and PA participation, and level of PA, after controlling for confounding. Results Data from 1260 respondents showed that 24% of persons with MS did not participate in any PA. Remoteness was not associated with the participation in any PA (OR 1.04; 89% highest density probability interval (HDPI) estimate 0.88, 1.22). Amongst those with any PA (n = 960), those living in more remote areas had, on average, higher levels of PA (RR 1.21; 89% HDPI estimate 1.11, 1.34). Conclusions Physical activity promotion does not need to differ based on geographical location

The impact of the Australian Black Summer Bushfires and the COVID-19 pandemic on wellbeing in persons with multiple sclerosis; preparation for future and ongoing crises

Purpose The Australian multiple sclerosis (MS) community experienced two recent major crises, widespread bushfires and the COVID 19 pandemic. We aimed to understand the needs of persons with MS during times of crisis. Materials and methods A consumer-directed mixed-method study. We included an online survey, semi-structured interviews, and a workshop with persons with MS, carers, healthcare professionals, and disability advocates. Data were collected via: (1) 176 people completing online surveys to identify crisis concerns and communications, (2) 29 people completing online interviews on bushfire and pandemic impact, and (3) 13 people participating in a crises-priorities workshop. Descriptive data were calculated for survey response, and a general inductive analytical approach was taken with interview and workshop responses. Results The most significant concerns were bushfire smoke exposure and disease-modifying-medication and susceptibility to COVID-19 (66% and 63% mean concern score, respectively). Interviews indicated crises experiences from the bushfires, and the pandemic overlapped respective of changes in mood and symptom stability. For bushfires, a need for future preparations, and for the pandemic, the benefits of social restrictions, disclosing personal health information and increased care burden were important. Conclusions Multiple crises challenged the MS community but offered lessons for healthcare in future crises. Continued progress in centralised crisis information, with considered use of telehealth and rural healthcare support, is needed

LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation

Schistosomes, major parasitic helminths, express numerous glycoconjugates that provoke humoral and cellular immune responses in the infected human host. The main pathology in schistosomiasis is due to the formation of granulomas around tissue-trapped eggs and the resulting organ damage. By using a mouse model of induction of granulomas by hepatic implantation of antigen-coated beads, it has been determined that the glycan part of schistosomal soluble egg antigens (SEA) initiates granulomogenesis. To identify which individual glycan elements in this complex SEA mixture are granulomogenic, we have tested in the same mouse model conjugates of various synthetic oligosaccharides characteristic for schistosome eggs, including GalNAc beta 1-4GlcNAc (LacdiNAc, LDN), Gal beta 1-4(Fuc alpha 1-3)GlcNAc (Lewis(x)), Fuc alpha 1-2Fuc alpha 1-3GlcNAc (DF-Gn), and Fuc alpha 1-3GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc (F-LDN-F). Ribonuclease (RNase) A and B, and different fetuin glycoforms were included as controls. Only beads that carry glycoconjugates with terminal LacdiNAc or Gal beta 1-4GlcNAc (LacNAc, LN) elements gave rise to granulomas, with macrophage, lymphocyte, and eosinophil levels similar to the granulomatous lesions caused by schistosome eggs in a natural infection. Uncoated beads, and beads coated with fucosylated glycoconjugates or glycoconjugates lacking terminally exposed Gal or GalNAc, only attracted a monolayer of macrophages. These results indicate that the formation of hepatic granulomas is triggered specifically by glycoconjugates which carry terminal LacNAc or LacdiNAc, both constituents of the schistosome egg

Comparing the effectiveness, safety and tolerability of interventions for depressive symptoms in people with multiple sclerosis: A systematic review and network meta-analysis protocol

Background Comorbid depression is prevalent in people with multiple sclerosis (MS). Depression is commonly untreated or undertreated, thus, there is a need for effective and safe interventions and current guidelines recommend psychological and pharmaceutical interventions for people with MS. However, research suggests that other interventions, such as exercise, could also be effective. The comparative efficacy and safety of intervention modalities have not been quantified. We plan to conduct a systematic review and network meta-analysis to compare efficacy and safety of psychological, pharmaceutical, physical and magnetic stimulation interventions for depression in people with MS. Methods and analysis We will search EMBASE, Medline, Cochrane CENTRAL, APA PsycINFO, Web of Science, CINAHL and PEDro from inception to 31 December 2021. Search terms will stem from three concepts: MS, depression and randomised controlled trials. Included studies will be randomised controlled trials, where participants are people with MS randomised to receive one of the aforementioned intervention types, and depression or depressive symptoms is the primary outcome, only outcome or secondary outcome with an a priori power calculation. Screening, data extraction and risk of bias assessment (using the Risk of Bias 2 tool) will be conducted independently by two reviewers. If possible, we will synthesise the evidence by fitting a frequentist network meta-analysis model with multivariate random effects, or a pairwise random-effects meta-analysis model. For each model, efficacy will be measured using a standardised mean difference, and safety using an OR. We plan to provide summary measures including forest plots, a geometry of the network, surface under the cumulative ranking curve, and a league table, and perform subgroup analyses. Otherwise, a narrative review will be provided. Ethics and dissemination Ethics is not required for a systematic review and network meta-analysis. Results will be published in a peer reviewed journal

Cost-effectiveness of pharmacogenomics-guided prescribing to prevent gene-drug-related deaths: a decision-analytic model

Aim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing potential drug-related deaths have been categorized as "essential" by the Dutch Pharmacogenetics Working Group (DPWG). The collective clinical impact and cost-effectiveness of this sub-set is yet undetermined. Therefore, we aim to assess impact and cost-effectiveness of "essential" PGx tests for prevention of gene-drug-related deaths, when adopted nation-wide. Methods: We used a decision-analytic model to quantify the number and cost per gene-drug-related death prevented, from a 1-year Dutch healthcare perspective. The modelled intervention is a single gene PGx-test for CYP2C19, DPYD, TPMT or UGT1A1 to guide prescribing based on the DPWG recommendations among patients in the Netherlands initiating interacting drugs (clopidogrel, capecitabine, systemic fluorouracil, azathioprine, mercaptopurine, tioguanine or irinotecan). Results: For 148,128 patients initiating one of seven drugs in a given year, costs for PGx-testing, interpretation, and drugs would increase by euro21.4 million. Of these drug initiators, 35,762 (24.1%) would require an alternative dose or drug. PGx-guided prescribing would relatively reduce gene-drug related mortality by 10.6% (range per DGI: 8.1-14.5%) and prevent 419 (0.3% of initiators) deaths a year. Cost-effectiveness is estimated at euro51,000 per prevented gene-drug-related death (range per DGI: euro-752,000-euro633,000). Conclusion: Adoption of PGx-guided prescribing for "essential" DGIs potentially saves the lives of 0.3% of drug initiators, at reasonable costs.</p

Cost-Effectiveness of Pharmacogenomics-Guided Prescribing to Prevent Gene-Drug-Related Deaths: A Decision-Analytic Model

Aim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing potential drug-related deaths have been categorized as "essential" by the Dutch Pharmacogenetics Working Group (DPWG). The collective clinical impact and cost-effectiveness of this sub-set is yet undetermined. Therefore, we aim to assess impact and cost-effectiveness of "essential" PGx tests for prevention of gene-drug-related deaths, when adopted nation-wide.Methods: We used a decision-analytic model to quantify the number and cost per gene-drug-related death prevented, from a 1-year Dutch healthcare perspective. The modelled intervention is a single gene PGx-test for CYP2C19, DPYD, TPMT or UGT1A1 to guide prescribing based on the DPWG recommendations among patients in the Netherlands initiating interacting drugs (clopidogrel, capecitabine, systemic fluorouracil, azathioprine, mercaptopurine, tioguanine or irinotecan).Results: For 148,128 patients initiating one of seven drugs in a given year, costs for PGx-testing, interpretation, and drugs would increase by euro21.4 million. Of these drug initiators, 35,762 (24.1%) would require an alternative dose or drug. PGx-guided prescribing would relatively reduce gene-drug related mortality by 10.6% (range per DGI: 8.1-14.5%) and prevent 419 (0.3% of initiators) deaths a year. Cost-effectiveness is estimated at euro51,000 per prevented gene-drug-related death (range per DGI: euro-752,000-euro633,000).Conclusion: Adoption of PGx-guided prescribing for "essential" DGIs potentially saves the lives of 0.3% of drug initiators, at reasonable costs.Personalised Therapeutic

The effect of the Australian bushfires and the COVID-19 pandemic on health behaviours in people with multiple sclerosis

Background Crises and disasters disproportionally impact people with chronic health conditions such as multiple sclerosis (MS). Objective To assess the impact of the COVID-19 pandemic and the Australian Black Summer Bushfires on health behaviours in people with MS. Methods People with MS, carers, healthcare and advocacy professionals were recruited online between May-July 2020 for an online survey and telephone interviews. Results Survey items relating to health behaviours were completed by 113 people with MS, and 18 people with MS, 4 MS advocates, 5 healthcare professionals, and 2 carers were interviewed. The bushfires affected 34.5% and the pandemic affected 74.3% of survey participants with MS. The pandemic and bushfires caused a decrease in physical activity in 53.8% and 55.3% of participants respectively, as well as increases in unhealthy eating (43.6% and 24.3% respectively) and alcohol consumption (35.4% and 10.5% respectively), and a decrease in typical sleeping patterns (40.5% and 39.5% respectively). Conversely, 27.5% of participants reported an increase in physical activity during the pandemic. Interview data detailed the circumstances and motivations for changes in health behaviours, as well as consequences, including reduced mobility, fitness, mood disturbances, and weight gain. Conclusion There is a need to increase support and health promotion for people with MS to maintain or initiate positive health behaviours, especially in times of adversity