An Interactive Web Application for the Statistical Analysis of Continuous Glucose Monitoring Data in Epidemiological Studies.

MOTIVATION: Continuous glucose monitoring (CGM) systems are an essential part of novel technology in diabetes management and care. CGM studies have become increasingly popular among researchers, healthcare professionals, and people with diabetes due to the large amount of useful information that can be collected using CGM systems. The analysis of the data from these studies for research purposes, however, remains a challenge due to the characteristics and large volume of the data. RESULTS: Currently, there are no publicly available interactive software applications that can perform statistical analyses and visualization of data from CGM studies. With the rapidly increasing popularity of CGM studies, such an application is becoming necessary for anyone who works with these large CGM datasets, in particular for those with little background in programming or statistics. CGMStatsAnalyser is a publicly available, user-friendly, web-based application, which can be used to interactively visualize, summarize, and statistically analyze voluminous and complex CGM datasets together with the subject characteristics with ease.

Epididymitis rates in Australian hospitals 2009-2018: ecological analysis.

OBJECTIVES: To investigate rates of acute epididymitis diagnosed in Australian hospital settings. METHODS: Yearly hospital admission and emergency department (ED) rates of epididymitis as primary diagnoses were calculated for 15-44-year-old men for three states (Victoria, New South Wales, Queensland) from 2009 to 2014 using population denominators. Zero inflated Poisson regression models were used to analyse variation in rates by year, age, and residential area. Additionally, we investigated national epididymitis admission trends from 2009 to 2018 using generalised linear models. RESULTS: Between 2009 and 2014, there was a total of 7375 admissions and 17 281 ED presentations for which epididymitis was the main reason for care. Most epididymitis diagnoses (94.0% in admissions, 99.7% in EDs) were without abscess, and 2.5% of admissions were for chlamydial epididymitis. Almost a quarter (23.3%) of epididymitis diagnosed in EDs resulted in hospital admission. In 2014, the epididymitis rate per 100 000 men was 38.7 in admissions and 91.9 in EDs. Comparing 2014 with 2009, the overall epididymitis diagnosis rate increased in admissions by 32% (adjusted incident rate ratio (aIRR) 1.32, 95% CI 1.20 to 1.44) and in ED attendances by 40% (aIRR 1.40, 95% CI 1.31 to 1.49). By age, the highest rates were among men 35-44 years in admissions and men 15-24 years in EDs. National admission rates of epididymitis during 2009-2018 showed a similar pattern. CONCLUSION: Rates of epididymitis diagnosis in hospital admission and ED presentations increased. Different age-related rates in these settings suggest a different aetiology or differential severity by age group.

Multiple imputation methods for handling missing values in longitudinal studies with sampling weights: Comparison of methods implemented in Stata.

Many analyses of longitudinal cohorts require incorporating sampling weights to account for unequal sampling probabilities of participants, as well as the use of multiple imputation (MI) for dealing with missing data. However, there is no guidance on how MI and sampling weights should be implemented together. We simulated a target population based on the Australian Bureau of Statistics Estimated Resident Population and drew 1000 random samples dependent on three design variables to mimic the Longitudinal Study of Australian Children. The target analysis was the weighted prevalence of overweight/obesity over childhood. We evaluated the performance of several MI approaches available in Stata, based on multivariate normal imputation (MVNI), fully conditional specification (FCS) and twofold FCS: a weighted imputation model, imputing missing data separately for each quintile sampling weight grouping, including the design stratum indicator in the imputation model, and using sampling weights as a covariate in the imputation model. Approaches based on available cases and inverse probability weighting (IPW), with time-varying weights, were also compared. We observed severe issues of convergence with FCS and twofold FCS. All MVNI-based approaches performed similarly, producing minimal bias and nominal coverage, except for when imputation was conducted separately for each quintile sampling weight group. IPW performed equally as well as MVNI-based approaches in terms of bias, however, was less precise. In similar longitudinal studies, we recommend using MVNI with the design stratum as a covariate in the imputation model. If this is unknown, including the sampling weight as a covariate is an appropriate alternative.

Metabolomic Biomarkers of Multiple Sclerosis: A Systematic Review.

BACKGROUND: Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald's clinical criteria are currently utilized tools in diagnosing multiple sclerosis. However, a more conclusive, consistent, and efficient way of diagnosing multiple sclerosis (MS) is yet to be discovered. A potential biomarker, discovered using advances in high-throughput sequencing such as nuclear magnetic resonance (NMR) spectroscopy and other "Omics"-based techniques, may make diagnosis and prognosis more reliable resulting in a more personalized and targeted treatment regime and improved outcomes. The aim of this review was to systematically search the literature for potential biomarkers from any bodily fluid that could consistently and accurately diagnose MS and/or indicate disease progression. METHODS: A systematic literature review of EMBASE, PubMed (MEDLINE), The Cochrane Library, and CINAHL databases produced over a thousand potential studies. Inclusion criteria stated studies with potential biomarker outcomes for people with MS were to be included in the review. Studies were limited to those with human participants who had a clinically defined diagnosis of MS and published in English, with no limit placed on date of publication or the type of bodily fluid sampled. RESULTS: A total of 1,805 studies were recorded from the literature search. A total of 1,760 studies were removed based on their abstract, with a further 18 removed after considering the full text. A total of 30 studies were considered relevant and had their data retrieved and analyzed. Due to the heterogeneity of focus and results from the refined studies, a narrative synthesis was favored. CONCLUSION: Several promising candidate biomarkers suitable for clinical application in MS have been studied. It is recommended follow-up studies with larger sample sizes be completed on several potential biomarkers.

Evaluating the efficacy and safety of GKT137831 in adults with type 1 diabetes and persistently elevated urinary albumin excretion: a statistical analysis plan.

BACKGROUND: The investigational medicinal product GKT137831 is a selective inhibitor of NOX 1 and 4 isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes, which has the potential to ameliorate diabetic kidney disease. An investigator-initiated, double-blind, randomised, placebo-controlled, multicentre phase 2 clinical trial started recruitment in December 2017, with the aim of evaluating the efficacy and safety of GKT13783, in adults with type 1 diabetes mellitus and persistently elevated urinary albumin excretion over a period of 48 weeks. METHODS/DESIGN: The trial is currently recruiting in Australia and New Zealand, with recruitment expected to end on 30 June 2020. The primary outcome measure of the trial is the urinary albumin excretion level measured at 48 weeks of treatment. This statistical analysis plan presents an update to the published trial protocol and provides a comprehensive description of the statistical methods that will be used for the analysis of the data from this trial. In doing so, we follow the "Guidelines for the content of statistical analysis plans in clinical trials" to support transparency and reproducibility of the trial findings. DISCUSSION: With the use of this prior statistical analysis plan, we aim to minimise bias in the reporting of the findings of this trial, which evaluates the investigational medicinal product GKT137831. The results of the trial are expected to be published in 2022. TRIAL REGISTRATION: ANZCTR registry: ACTRN12617001187336. Registered on 14 July 2017. Universal Trial Number: U1111-1187-2609; Protocol number: T1DGKT137831; Genkyotex trial number: GSN000241.

A physician-initiated double-blind, randomised, placebo-controlled, phase 2 study evaluating the efficacy and safety of inhibition of NADPH oxidase with the first-in-class Nox-1/4 inhibitor, GKT137831, in adults with type 1 diabetes and persistently elevated urinary albumin excretion: Protocol and statistical considerations.

PURPOSE: Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease. This study will evaluate the effect of GKT137831 in treating clinical diabetic kidney disease. DESIGN: This is a multi-center, randomized, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 400 mg BID for 48 weeks. The study will randomize 142 participants who have persistent albuminuria and estimated glomerular filtration rate (eGFR) at baseline of at least 40 ml/min/1.73m2. PRIMARY OUTCOME MEASURES: Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR. CONCLUSION: This study is important because it may identify a new way of slowing renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.

On the path together: Experiences of partners of people with multiple sclerosis of the impact of lifestyle modification on their relationship.

Multiple sclerosis (MS) has a major impact on the relationship of couples living with the illness. Although some positives of dealing with MS as a couple have been identified, MS has been associated with higher rates of relationship breakdown and worse Quality of Life (QOL) for both people in the relationship, especially if the person with MS experiences a decline in mental or physical health or develops disability. Modification of lifestyle-related risk factors has been associated with improved outcomes for people with MS, including physical and mental health-related QOL, and these improved outcomes may lead to improved experiences for their partners. We aimed to explore the perspectives and experiences of the partners of people with MS, when the people with MS had undertaken an intensive residential workshop regarding healthy lifestyle, to understand the impact of MS and lifestyle modification on these partners' experiences of their relationship. Within the framework of Heidegger's interpretive phenomenology, semi-structured interviews were thematically analysed. Participants were in a spousal relationship with people with MS who had attended an intensive residential workshop regarding modification of lifestyle-related risk factors between 2002 and 2016. Participants lived in Australia, New Zealand, the United Kingdom and Europe. Three major themes were identified relating to the couple's relationships: providing support, remaining connected and togetherness. Aspects of these themes, not commonly previously reported, included the personal and relationship benefits experienced from providing support with lifestyle modification, improved communication, and the resultant greater sense of closeness. These experiences of partners of people with MS improve our understanding of both the complexities of living with MS and adopting lifestyle modification, and suggest some potential benefits to relationships.

Trends in diagnosis of pelvic inflammatory disease in an Australian sexual health clinic, 2002-16: before and after clinical audit feedback.

Background A 2006 Australian sexual health clinic audit of pelvic inflammatory disease (PID) diagnosis rates found variability between doctors. Doctors were given audit feedback towards increasing diagnosis and reducing variability. The clinic implemented other improvements to increase capacity. This study investigated PID diagnosis time trends before and after feedback. METHODS: Yearly PID diagnosis rates for women aged 16-49 years attending the clinic (2002-16) were calculated. Using multivariable generalised linear mixed models, adjusted for patient risk and lower genital infection (any of chlamydia, gonorrhoea, Mycoplasma genitalium, bacterial vaginosis) and stratified by before (2002-June 2007) and after (July 2007-2016) feedback, we assessed if PID rates changed over time, accounting for between-doctor variability. RESULTS: During 2002-16, 144 doctors undertook 84476 female consultations and diagnosed 1755 (2.1%, 95% confidence interval (CI) 2.0-2.2) with PID. Comparing 2002-03 to 2015-16, the yearly PID rate increased; 0.8% (37/4836) to 2.9% (209/7088). Comparing before and after feedback more women reported any symptoms at triage (35.1%-47.2%) or had a lower genital infection diagnosed (10.1%-14.9%). After feedback, PID rates increased by 8% yearly (incidence rate ratio (IRR) 1.08, 95% CI 1.06-1.11), but were unchanged (adjusted IRR (aIRR) 1.01, 95% CI 0.98-1.03) after adjustment for patient characteristics. Factors associated with PID were self-reported symptoms, younger age and a lower genital infection. Lower variability in doctor-specific rates was observed after feedback. CONCLUSIONS: Increasing PID diagnosis rates appeared to be driven by a greater female patient risk profile, influenced by increased capacity following service improvements.

Taking active steps: Changes made by partners of people with multiple sclerosis who undertake lifestyle modification.

BACKGROUND: Multiple sclerosis (MS), a demyelinating condition of the central nervous system with an unpredictable course, has a major impact on the lives of people with MS. Partners of people with MS may be significantly affected by the diagnosis, management and uncertainty around disease progression and may provide substantial support and care. Modification of lifestyle risk factors in conjunction with standard medical management has been associated with improved physical and mental quality of life. Adopting major lifestyle modification may have a multi-faceted impact on the person with MS and their partner. Experiences of partners of people with MS have been previously explored, but the experiences of partners of people with MS who adopt this strategy have not. As part of a larger study that aimed to explore partners' lived experiences of and attitudes towards MS and lifestyle modification, this study reports the active steps and significant changes partners undertook to assist the person with MS and, at times, to also modify their own lives. DESIGN: Within an interpretive framework, using Heidegger's phenomenological philosophy, a qualitative study of semi-structured interviews was conducted. PARTICIPANTS: Aged greater than 18 years and in a spousal relationship with a person with MS who had undertaken an intensive residential lifestyle educational intervention promoting healthy lifestyle. RESULTS: Themes identified were: adjusting to lifestyle modification, understanding motivations and practical aspects of adjustment; seeking knowledge and support, exploring the ways partners sought positive support for themselves and the person with MS and abandoned negative influences; and embracing well-being, commitment and change, describing the major changes that partners made to their lives professionally and personally. CONCLUSIONS: The experiences of these partners provide clinicians with insight into potential motivations and outcomes of lifestyle modification and suggest potentially positive aspects for those directly and indirectly affected by MS.

Associations of demographic and clinical factors with depression over 2.5-years in an international prospective cohort of people living with MS.

BACKGROUND: Depression is highly prevalent among people with MS, and determinants thereof would be useful. OBJECTIVES: We examined the relationship of demographic and clinical factors with positive depression-screen and change in depression over 2.5 years in people with MS. METHODS: Positive depression-screen assessed by Patient Health Questionnaire (PHQ)-2 and PHQ-9. Associations of demographic and clinical factors with depression-screen and change thereof assessed using multivariable regression models, adjusted for age, sex, disability, fatigue, antidepressant use, and baseline PHQ-2, as appropriate. RESULTS: Overweight/obese BMI, comorbidity number, fatigue, and disability were associated with positive depression-screen, while married/partnered state, being employed, higher perceived socioeconomic status, and greater education were inversely associated with depression-screen. After adjustment, only marital status, socioeconomic status, antidepressant medication use, and fatigue were associated with risk of newly positive depression-screen. MS type, relapse number and immunomodulatory medication use were not associated with depression-screen after controlling for disability and fatigue. CONCLUSION: In a large prospective cohort study of depression in people with MS, we substantiated several potential determinants of a positive depression-screen and depression trajectory, particularly fatigue. Given that fatigue is the most common and most significant clinical symptom for people with MS, efforts to reduce fatigue may have follow-on benefits for reducing depression.

Differential multiple sclerosis treatment allocation between Australia and New Zealand associated with clinical outcomes but not mood or quality of life.

BACKGROUND: Differential treatment allocation may impact on clinical phenotype in MS and in turn upon quality of life (QoL). OBJECTIVES: (a) Investigate the association between disease-modifying drugs (DMDs) use and relapse frequency, disability, clinically significant fatigue, and physical and mental health-related QoL among participants with MS residing in Australia and New Zealand (NZ); (b) assess whether these associations differed between Australia and NZ. METHODS: Disability and fatigue were measured by PDDS and FSS, respectively. QoL was assessed by MSQOL-54. Associations were assessed by binomial and multinomial logistic regression, as appropriate. Multivariable models were adjusted for demographic and clinical covariates, as appropriate. RESULTS: 837 participants (627 from Australia; 210 from NZ) were identified from an online cohort of people with MS. First- and second-generation DMD use was associated with higher adjusted-odds of fatigue and disability, though not with 12-month relapse number. DMD use was not independently associated with physical or mental QoL. The association of first-generation DMD use with moderate disability differed between nations, such that treatment was associated with lower odds in Australia but not in NZ; a similar but a small difference was found for severe disability. No differences were seen in the DMD association with relapse number, nor with fatigue or QoL, between Australia and NZ. CONCLUSION: The differential treatment allocation associations in NZ are evident in the DMD-disability association, but there is no evidence that this treatment regimen has negative associations with fatigue, mood, or QoL.

Effectiveness of Exercise Interventions for Pain Reduction in People With Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review the evidence of the effect of exercise compared with passive control on pain in people with multiple sclerosis. DATA SOURCE AND STUDY SELECTION: Five electronic databases were searched for randomized controlled trials published up to March 2017 that recruited people with multiple sclerosis where exercise was the intervention and pain was an outcome (PROSPERO registration number CRD42017060489). STATISTICAL ANALYSIS: A random-effects meta-analysis was conducted to estimate the standardized mean difference of the effect of exercise on pain between treatment and control groups. We assessed risk of bias, fitted meta-regression models to explore heterogeneity between studies, and assessed small study effects. DATA SYNTHESIS: Ten studies met the inclusion criteria (total sample size=389), and all studies were at high risk of bias. We found that exercise interventions were associated with less pain compared with passive control groups (standardized mean difference=-.46; 95% CI, -.92 to .00). There was high between-study heterogeneity (I2=77.0%), which was not explained by the prespecified study characteristics. There was also some evidence of small study effects. CONCLUSION: This is the first systematic review of the effect of exercise interventions on pain in people with multiple sclerosis, a chronic neurological disorder that affects 2.5 million people. We found some evidence that exercise compared with passive control alleviates pain in this population, but there were limitations in reporting and study quality with high risk of bias of individual studies and heterogeneity between studies.

Longitudinal Associations of Modifiable Lifestyle Factors With Positive Depression-Screen Over 2.5-Years in an International Cohort of People Living With Multiple Sclerosis.

Background: Depression is common and has a significant impact on quality of life for many people with multiple sclerosis (MS). A preventive management approach via modification of lifestyle risk factors holds potential benefits. We examined the relationship between modifiable lifestyle factors and depression risk and the change in depression over 2.5 years. Methods: Sample recruited using online platforms. 2,224 (88.9%) at baseline and 1,309 (93.4%) at 2.5 years follow up completed the necessary survey data. Depression risk was measured by the Patient Health Questionnaire-2 (PHQ-2) at baseline and Patient Health Questionniare-9 (PHQ-9) at 2.5-years follow-up. Multivariable regression models assessed the relationships between lifestyle factors and depression risk, adjusted for sex, age, fatigue, disability, antidepressant medication use, and baseline depression score, as appropriate. Results: The prevalence of depression risk at 2.5-years follow-up in this cohort was 14.5% using the PHQ-2 and 21.7% using the PHQ-9. Moderate alcohol intake, being a non-smoker, diet quality, no meat or dairy intake, vitamin D supplementation, omega 3 supplement use, regular exercise, and meditation at baseline were associated with lower frequencies of positive depression-screen 2.5 years later. Moderate alcohol intake was associated with greater likelihood of becoming depression-free and a lower likelihood of becoming depressed at 2.5-years follow-up. Meditating at least once a week was associated with a decreased frequency of losing depression risk, against our expectation. After adjusting for potential confounders, smoking, diet, physical activity, and vitamin D and omega-3 supplementation were not associated with a change in risk for depression. Conclusion: In a large prospective cohort study of people with MS and depression, in line with the emerging treatment paradigm of early intervention, these results suggest a role for some lifestyle factors in depression risk. Further studies should endeavor to explore the impact of positive lifestyle change and improving depression in people living with MS.

Longitudinal Associations of the Healthy Lifestyle Index Score With Quality of Life in People With Multiple Sclerosis: A Prospective Cohort Study.

Objective: To explore the association between combined lifestyle risk factors with quality of life in people with multiple sclerosis (MS) over 2.5 years. Methods: People with MS were recruited to participate in a comprehensive online survey regarding their demographic and clinical characteristics, health-related quality of life (HRQOL), and lifestyle behaviors including physical activity, alcohol consumption, cigarette smoking, body mass index, and dietary habits measured at baseline and 2.5-year follow-up. A combined healthy lifestyle index score (HLIS) was constructed by assigning scores of 0-4 to each of the lifestyle risk factors, for which higher values indicate healthier lifestyle behavior. Multivariable linear regression modeling was used to assess whether the HLIS at baseline was associated with the physical and mental HRQOL over the study period in this sample of people with MS. Results: Of 2,466 participants with confirmed MS, 1,401 (57%) completed the follow-up. Multivariable linear regression analyses demonstrated that every 5-point increase (of a possible total of 20) in the baseline HLIS was associated with 1.7 (95% CI: 0.2-3.2) and 2.5 (95% CI: 1.0-4.0) higher scores in the change in physical and mental HRQOL components from baseline to follow-up respectively. Conclusion: Findings suggest the importance of healthy lifestyle behavior in quality of life in MS. A healthy lifestyle program focusing on these behaviors has the potential to positively influence health-related quality of life for people with MS.

Gestational Age and the Cord Blood Lipidomic Profile in Late Preterm and Term Infants.

BACKGROUND: Lipid metabolism is vital to fetal development and cardiometabolic health and the final weeks of gestation are known to be a time of intense metabolic activity. New techniques such as lipidomics allow investigation of a complex lipidomic profile in infants. OBJECTIVES: This research aimed to (1) describe variations in lipidomic profile in late preterm and term infants and (2) compare variations to an adult lipidomic profile with known clinical implications. METHODS: The Barwon Infant Study (n = 1,074) is a population-derived pre-birth cohort study. The lipidomic profile of cord blood was measured by liquid chromatography-mass spectrometry in 225 participants and the association between gestational age and lipidomic profile was investigated using multiple linear regression adjusting for birth weight, exposure to labour, and infant sex. Patterns of association with gestational age across the lipidomic profile were compared with associations between body mass index (BMI) and lipidomic profile observed among adults in the San Antonia Family Heart Study (n = 994). RESULTS: Gestational age was independently associated with the abundances of 39% of lipid species. Variations in the lipidomic profile with increasing gestational age were comparable to some variations observed in association with increasing BMI among adults. CONCLUSION: There is a strong relationship between gestational age and the cord blood lipid profile at birth, providing further evidence for the importance of metabolic changes of late gestation. A number of the variations in the lipid profile with increasing gestational age are analogous to differences observed in the adult lipid profile with an increasing BMI.

Rates of pelvic inflammatory disease and ectopic pregnancy in Australia, 2009-2014: ecological analysis of hospital data.

OBJECTIVE: To analyse yearly rates of pelvic inflammatory disease (PID) and ectopic pregnancy (EP) diagnosed in hospital settings in Australia from 2009 to 2014. METHODS: We calculated yearly PID and EP diagnosis rates in three states (Victoria, New South Wales, Queensland) for women aged 15-44 years using hospital admissions and emergency department (ED) attendance data, with population and live birth denominators. We stratified PID diagnoses as chlamydial-related or gonorrhoeal-related (Chlamydia trachomatis (CT)-related or Neisseria gonorrhoeae (NG)-related), acute, unspecified and chronic, and analysed variations by year, age and residential area using Poisson regression models. RESULTS: For PID, the rate of all admissions in 2014 was 63.3 per 100 000 women (95% CI 60.8 to 65.9) and of all presentations in EDs was 97.0 per 100 000 women (95% CI 93.9 to 100.2). Comparing 2014 with 2009, the rate of all PID admissions did not change, but the rate of all presentations in EDs increased (adjusted incidence rate ratio (aIRR) 1.34, 95% CI 1.24 to 1.45), and for admissions by PID category was higher for CT-related or NG-related PID (aIRR 1.73, 95% CI 1.31 to 2.28) and unspecified PID (aIRR 1.09, 95% CI 1.00 to 1.19), and lower for chronic PID (aIRR 0.84, 95% CI 0.74 to 0.95). For EP, in 2014 the rate of all admissions was 17.4 (95% CI 16.9 to 17.9) per 1000 live births and of all ED presentations was 15.6 (95% CI 15.1 to 16.1). Comparing 2014 with 2009, the rates of all EP admissions (aIRR 1.06, 95% CI 1.04 to 1.08) and rates in EDs (aIRR 1.24, 95% CI 1.18 to 1.31) were higher. CONCLUSIONS: PID and EP remain important causes of hospital admissions for female STI-associated complications. Hospital EDs care for more PID cases than inpatient departments, particularly for young women. Updated primary care data are needed to better understand PID epidemiology and healthcare usage.

Health outcomes and adherence to a healthy lifestyle after a multimodal intervention in people with multiple sclerosis: Three year follow-up.

BACKGROUND: Modifiable risk factors such as smoking and sedentary lifestyle adversely affect multiple sclerosis (MS) progression. Few multimodal behavioural interventions have been conducted for people with MS, and follow-up beyond 1 year is rare for lifestyle interventions. This study assessed adoption and adherence to healthy lifestyle behaviours and health outcomes 3 years after a lifestyle modification intervention, using generalized estimating equation models to account for within-participant correlation over time. METHODS: 95 people with MS completed baseline surveys before participating in 5-day MS lifestyle risk-factor modification workshops. 76 and 78 participants completed the 1-year and 3-year follow-up surveys respectively. Mean age at 3-year follow-up was 47 years, 72% were female, most (62.8%) had MS for 5 years or less, and 73% had relapsing remitting MS (RRMS). RESULTS: Compared to baseline, participants reported clinically meaningful increases in physical (mean difference (MD): 8.0, 95% Confidence Interval (CI): 5.2-10.8) and mental health (MD: 9.2, CI: 5.8-12.6) quality of life (QOL) at 1-year, and physical (MD: 8.7, CI: 5.3-12.2) and mental health (MD: 8.0, CI: 4.2-11.8) QOL at 3-year follow-up. There was a small decrease in disability from baseline to 1-year follow-up (MD: 0.9, CI: 0.9,1.0) and to 3-year follow-up (MD: 1.0, CI: 0.9,1.0), which was not clinically meaningful. Of those with RRMS, compared to baseline, fewer had a relapse during the year before 1-year follow-up (OR: 0.1, CI 0.0-0.2) and 3-year follow-up (OR: 0.15, CI 0.06-0.33). Participants' healthy diet score, the proportion meditating ≥1 hours a week, supplementing with ≥ 5000IU vitamin D daily, and supplementing with omega-3 flaxseed oil increased at 1-year follow-up and was sustained, although slightly lower at 3-year follow-up. However, there was no evidence for a change in physical activity and not enough smokers to make meaningful comparisons. Medication use increased at 1-year follow-up and at 3-year follow-up. CONCLUSION: The results provide evidence that lifestyle risk factor modification is feasible and sustainable over time, in a small self-selected and motivated sample of people with MS. Furthermore, participation in a lifestyle intervention is not associated with a decrease in MS medication use.

The Efficacy of Psychological Interventions for Managing Fatigue in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system. Fatigue is commonly reported by people with MS (PwMS). MS-related fatigue severely affects daily activities, employment, socioeconomic status, and quality of life. OBJECTIVE: We conducted this systematic review and meta-analysis to determine whether psychological interventions are effective in managing fatigue in PwMS. DATA SOURCES: We performed systematic searches of Medline, EMBASE, PsycINFO, and CINAHL to identify relevant articles published from database inception to April 5, 2017. Reference lists from relevant reviews were also searched. STUDY SELECTION AND DESIGN: Two independent reviewers screened the papers, extracted data, and appraised the included studies. A clinical psychologist verified whether interventions were psychological approaches. A narrative synthesis was conducted for all included studies. For relevant randomized controlled trials that reported sufficient information to determine standardized mean differences (SMDs) and 95% confidence intervals (CIs), meta-analyses were conducted using a random-effects model. RESULTS: Of the 353 identified articles, 20 studies with 1,249 PwMS were included in this systematic review. Narrative synthesis revealed that psychological interventions reduced fatigue in PwMS. Meta-analyses revealed that cognitive behavioral therapy decreased levels of fatigue compared with non-active controls (SMD = -0.32; 95% CI: -0.63 to -0.01) and compared with active controls (relaxation or psychotherapy) (SMD = -0.71; 95% CI: -1.05 to -0.37). Meta-analyses further showed that both relaxation (SMD = -0.90; 95% CI: -1.30 to -0.51), and mindfulness interventions (SMD = -0.62; 95% CI: -1.12 to -0.12), compared with non-active control, decreased fatigue levels. The estimates of heterogeneity for the four meta-analyses varied between none and moderate. CONCLUSION: This study found that the use of psychological interventions for MS-related fatigue management reduced fatigue in PwMS. While psychological interventions are generally considered first-line therapy for MS-related fatigue, further studies are needed to explore the long-term effect of this therapy.

Psychological Shift in Partners of People with Multiple Sclerosis Who Undertake Lifestyle Modification: An Interpretive Phenomenological Study.

Introduction: Being in an intimate relationship with a person with multiple sclerosis (MS) may have a substantial impact on the partner's quality of life. Existing research has largely focused on negative impacts of MS for both people with MS (PwMS) and their partners and has sampled the population of partners of PwMS who have primarily adopted standard medical management only. Modifiable lifestyle factors have become increasingly recognized in the management of MS symptoms and disease progression. For partners of PwMS who have undertaken lifestyle modification as an additional strategy to minimize disease progression, the impacts, both positive and negative remain unexplored. This research is unique as it focuses on partners of PwMS who have attempted to adopt major lifestyle interventions outside of the prevailing paradigm of MS management. Aim: To explore and interpret the lived experiences of partners of PwMS who have adopted lifestyle modification, to understand partners' attitudes to and experiences of the effect of MS and lifestyle modification on their life, relationship and view of the future. Method: Design: a qualitative, interpretive, phenomenological study using semi-structured interviews. PARTICIPANTS: English-speaking; aged 18 years or more; in a spousal relationship for 12 months or more with a person with MS who had attended a residential lifestyle educational intervention and undertaken lifestyle modification. ANALYSIS: Interviews were recorded, transcribed verbatim and thematically analyzed using NVivo™ software. Results: Twenty-one partners were interviewed. This paper reports one of the study's themes, the psychological shift experienced by partners of PwMS. Sub-themes included adaptation; loss and grief; difficult emotions; reframing, re-evaluating and re-prioritizing; hope and optimism; empowerment and taking control; and self-awareness, greater understanding and personal growth. Conclusion: Partners of PwMS who have undertaken lifestyle modification experienced a broad range of psychological adjustments. Whilst reflecting the potential difficulties that partners of PwMS may experience, this group experienced a range of positive psychological changes that add to the literature regarding partners' potential experiences and may provide hope for those in partnerships with people with MS. This study provides themes to potentially inform a quantitative study of a larger population of partners of PwMS.

Health Outcomes and Lifestyle in a Sample of People With Multiple Sclerosis (HOLISM): Longitudinal and Validation Cohorts.

Objective: To report the methodology and summary data of the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) longitudinal and validation cohorts. We report (1) data on participation, socio-demographics, disease characteristics, medication use, modifiable lifestyle risk factor exposures, and health outcomes of the HOLISM longitudinal cohort 2.5-years post enrolment; (2) attrition at this 2.5-year wave; and (3) baseline characteristics of the associated HOLISM validation cohort. Methods: The HOLISM longitudinal study recruited people internationally with self-reported diagnosed multiple sclerosis (MS) through web 2.0 platforms and MS society newsletters. Participants, first recruited in 2012, were invited 2.5-years later to participate in a follow-up survey. At both time points, participants completed a comprehensive online questionnaire of socio-demographics, modifiable lifestyle exposures, and health outcomes using validated and researcher-designed tools. The same methodology was used to recruit a new sample: the HOLISM validation cohort. Characteristics were explored using summary measures. Results: Of 2,466 people with MS at baseline, 1,401 (56.8%) provided data at 2.5-year follow-up. Attrition was high, likely due to limited amount of contact information collected at baseline. Completion of the 2.5-year wave was associated with healthier lifestyle, and better health outcomes. Participants completing follow-up had diverse geographical location, were predominantly female, married, unemployed or retired. At 2.5-year follow-up, nearly 40% were overweight or obese, most were physically active, non-smokers, consumed little alcohol, used vitamin D/omega-3 supplements, and 42% reported current disease-modifying drug use. Thirty percentage of reported cane or gait disability, while 13% relied on major mobility supports (Patient Determined Disease Steps). Approximately half the respondents reported a comorbidity, 63% screened positive for clinically significant fatigue (Fatigue Severity Scale), and 22% screened positive for depression (Patient Health Questionnaire-9). The validation cohort's characteristics were mostly consistent with previously reported HOLISM baseline data. Conclusions: Exploring prospective associations of modifiable environmental/behavioral risk factors with health outcomes in this international longitudinal sample of people with MS will be beneficial to MS research. Impacts of attrition and selection bias will require consideration. The validation cohort provides opportunity for replication of previous findings, and also for temporal validation of predictive models derived from the HOLISM cohort.