A survey of women diagnosed with breast cancer experiencing oncology treatment-induced hot flushes: identification of specific characteristics as predictors of hot flush occurrence, frequency, and severity.

PURPOSE: More women diagnosed with breast cancer (BC) are living with oncology treatment-induced hot flushes (HFs). This Australian-based survey explores why some women experience more severe or ongoing HF and whether specific population characteristics are predictive of HF occurrence, frequency, and/or severity. METHODS: A non-probabilistic anonymous survey distributed online (Register4) and two Australian hospitals collected demographic and clinical information. Eligibility was consenting Australian-based women, 18 years and over, with a primary BC diagnosis. Analysis included linear and logistic regression models. RESULTS: A total of 324 survey responses were analyzed. Chemotherapy and hormone therapy were each associated with HF occurrence (aOR = 2.92, 95% CI [1.27, 6.70], p = 0.01; and aOR = 7.50, 95% CI [3.02, 18.62], p < 0.001) and in combination (aOR = 5.98, 95% CI [2.61, 13.69], p < 0.001). Increased self-reported anxiety at BC diagnosis was significantly associated with HF frequency and severity scores (aCO = 0.71, 95% CI [0.31, 1.12], p = 0.001; and aCO = 0.44, 95% CI [0.33, 0.55], p < 0.001). Postmenopausal women had significantly lower HF severity and frequency scores than premenopausal women (aCO = -0.93, 95% CI [-1.62, -0.25], p = 0.008; and aCO = -2.62, 95% CI [-5.14, -0.11], p = 0.041). CONCLUSIONS: Women with BC receiving chemotherapy and/or hormone therapy and premenopausal or experiencing elevated anxiety and/or stress will likely experience more severe oncology treatment-related HFs. IMPLICATIONS FOR CANCER SURVIVORS: HFs continue across the BC treatment trajectory with women >5-year survivorship still reporting life impacts, with premenopausal women at the time of BC diagnosis at higher risk of experiencing severe and more frequent oncology treatment-induced HFs than postmenopausal women. Women at high risk require information on methods to moderate HF potential life impacts and maintain treatment compliance.

MetaHD: A multivariate meta-analysis model for metabolomics data.

MOTIVATION: Meta-analysis methods widely-used for combining metabolomics data do not account for correlation between metabolites or missing values. Within- and between-study variability are also often overlooked. These can give results with inferior statistical properties, leading to misidentification of biomarkers. RESULTS: We propose a multivariate meta-analysis model for high-dimensional metabolomics data (MetaHD), which accommodates the correlation between metabolites, within- and between-study variances, and missing values. MetaHD can be used for integrating and collectively analysing individual-level metabolomics data generated from multiple studies as well as for combining summary estimates. We show that MetaHD leads to lower root mean square error compared to the existing approaches. Furthermore, we demonstrate that MetaHD, which exploits the borrowing strength between metabolites, could be particularly useful in the presence of missing data compared to univariate meta-analysis methods, which can return biased estimates in the presence of data missing at random. AVAILABILITY AND IMPLEMENTATION: The MetaHD R package can be downloaded through Comprehensive R Archive Network (CRAN) repository. A detailed vignette with example datasets and code to prepare data and analyses are available on https://bookdown.org/a2delivera/MetaHD/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effectiveness of an anti-inflammatory diet versus low-fat diet for knee osteoarthritis: the FEAST randomised controlled trial protocol.

INTRODUCTION: Chronic inflammation plays a key role in knee osteoarthritis pathophysiology and increases risk of comorbidities, yet most interventions do not typically target inflammation. Our study will investigate if an anti-inflammatory dietary programme is superior to a standard care low-fat dietary programme for improving knee pain, function and quality-of-life in people with knee osteoarthritis. METHODS AND ANALYSIS: The eFEct of an Anti-inflammatory diet for knee oSTeoarthritis study is a parallel-group, assessor-blinded, superiority randomised controlled trial. Following baseline assessment, 144 participants aged 45-85 years with symptomatic knee osteoarthritis will be randomly allocated to one of two treatment groups (1:1 ratio). Participants randomised to the anti-inflammatory dietary programme will receive six dietary consultations over 12 weeks (two in-person and four phone/videoconference) and additional educational and behaviour change resources. The consultations and resources emphasise nutrient-dense minimally processed anti-inflammatory foods and discourage proinflammatory processed foods. Participants randomised to the standard care low-fat dietary programme will receive three dietary consultations over 12 weeks (two in-person and one phone/videoconference) consisting of healthy eating advice and education based on the Australian Dietary Guidelines, reflecting usual care in Australia. Adherence will be assessed with 3-day food diaries. Outcomes are assessed at 12 weeks and 6 months. The primary outcome will be change from baseline to 12 weeks in the mean score on four Knee injury and Osteoarthritis Outcome Score (KOOS4) subscales: knee pain, symptoms, function in daily activities and knee-related quality of life. Secondary outcomes include change in individual KOOS subscale scores, patient-perceived improvement, health-related quality of life, body mass and composition using dual-energy X-ray absorptiometry, inflammatory (high-sensitivity C reactive protein, interleukins, tumour necrosis factor-α) and metabolic blood biomarkers (glucose, glycated haemoglobin (HbA1c), insulin, liver function, lipids), lower-limb function and physical activity. ETHICS AND DISSEMINATION: The study has received ethics approval from La Trobe University Human Ethics Committee. Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000440729.

Adiposity and cartilage lesions following ACL reconstruction.

OBJECTIVE: To determine if global, central, or peripheral adiposity is associated with prevalent and worsening cartilage lesions following anterior cruciate ligament reconstruction (ACLR). METHODS: In 107 individuals one-year post-ACLR, adiposity was assessed globally (body mass index), centrally (waist circumference), and peripherally (knee subcutaneous adipose tissue thickness) from magnetic resonance imaging (MRI). Tibiofemoral and patellofemoral cartilage lesions were assessed from knee MRIs at 1- and 5-years post-ACLR. Poisson regression evaluated the relation of adiposity with prevalent and worsening tibiofemoral and patellofemoral cartilage lesions adjusting for age, sex, and activity level. RESULTS: The prevalence ratios of adiposity with tibiofemoral (presence in 49%) and patellofemoral (44%) cartilage lesions ranged from 0.99 to 1.03. Adiposity was more strongly associated with longitudinal changes in tibiofemoral (worsening in 21%) and patellofemoral (44%) cartilage lesions. One-unit increase in global (kg/m2), central (cm), and peripheral (mm) adiposity was associated with a higher risk of worsening tibiofemoral cartilage lesions by 17% (risk ratios [95% confidence interval (CI)]: 1.17 [1.09 to 1.23]), 5% (1.05 [1.02 to 1.08]), and 9% (1.09 [1.03 to 1.16]), and patellofemoral cartilage lesions by 5% (1.05 [1.00 to 1.12]), 2% (1.02 [1.00 to 1.04]) and 2% (1.02 [1.00 to 1.04]), respectively. CONCLUSION: Greater adiposity was a risk factor for worsening cartilage lesions up to 5 years post-ACLR. Clinical interventions aimed at mitigating excess adiposity may be beneficial in preventive approaches for early post-traumatic osteoarthritis.

The longitudinal effects of the built environment on transportation and recreational walking, and differences by age and sex: systematic review protocol.

BACKGROUND: In high-income countries, the prevalence of physical inactivity and non-communicable diseases is high, and it is now well-established that insufficient physical activity is a risk factor for non-communicable diseases. Walking for recreation and transportation are effective means of improving population levels of physical activity. Research finds that the built environment (BE) can encourage or discourage walking behaviour, and this association varies for different age groups and sexes. This systematic review aims to synthesise longitudinal evidence to better understand how the BE affects recreational and transportation walking for different age groups (above 64 years and 18-64 years) and sexes in high-income countries. METHOD: We will use Scopus, PubMed, SPORTDiscus with Full Text (EBSCO), Business Source Complete (EBSCO), Art and Architecture Archive (Proquest), Avery Index to Architectural Periodicals (ProQuest), and Art, Design & Architecture Collection (ProQuest) databases to search for relevant studies. Reviewers will screen the search results according to pre-specified eligibility criteria for study inclusion in the review. Required data for the synthesis will be extracted from the included studies to answer the research questions. Further, the methodological quality of the studies included in this systematic review will be evaluated using an established instrument, and the resulting quality scores will be utilized in sensitivity analysis. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist will be followed when reporting the findings. DISCUSSION: This review will identify BE attributes that are likely to influence transportation and recreational walking for younger and older adults and different sexes in high-income countries. The findings will help policymakers with making decisions around walkable built environments for older and younger adults and different sexes to keep them healthy. TRIAL REGISTRATION: This protocol of the prospective systematic review is developed following PRISMA-P guidelines and is registered on the Prospective Register of Systematic Reviews (PROSPERO) (registration ID CRD42022351919).

Does the one-leg rise test reflect quadriceps strength in individuals following anterior cruciate ligament reconstruction?

OBJECTIVE: To explore if one-leg rise test performance is associated with quadriceps strength following anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional. PARTICIPANTS: 100 individuals (50 females, 50 males) aged 18-40 years, 9-36 months post-ACLR with ongoing knee symptoms (KOOS4 <80/100). MAIN OUTCOME MEASURES: Number of one-leg rise repetitions (using an adjustable-height plinth) and isometric quadriceps strength using isokinetic dynamometry (60° flexion, normalised to body mass). Multivariable fractional polynomial regression models adjusted for sex explored relationships between one-leg rise performance (repetitions) and quadriceps strength (Nm/kg) for each limb. RESULTS: A non-linear, increasing association between one-leg rise performance and quadriceps strength was observed, with the rate of increase attenuating at higher values of one-leg rise performance. Similar relationships were observed in the ACLR (ß = 0.15, 95%CI 0.10 to 0.20; adjusted r2 = 0.51) and contralateral limb (ß = 0.14, 95%CI 0.08 to 0.19; r2 = 0.42). CONCLUSION: The one-leg rise test can be an indicator of quadriceps strength in individuals after ACLR, enabling clinicians to easily monitor quadriceps strength recovery without specialised equipment. With the relationship between one-leg rise performance and quadriceps strength attenuating with a larger number of one-leg rises achieved, other factors (e.g., motivation, endurance) likely contribute to one-leg rise performance at higher values.

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study.

BACKGROUND: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance. METHODS: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation. RESULTS: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94. CONCLUSIONS: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research.

Higher diet quality is associated with short and long-term benefits on SF-6D health state utilities: a 5-year cohort study in an international sample of people with multiple sclerosis.

BACKGROUND/PURPOSE: Health state utilities (HSU) are a subjective measure of an individual's health-related quality of life (HRQoL), adjusted by societal or patient relative preference weights for living in different states of health-related quality of life (HRQoL), derived from patient-reported responses to multi-attribute utility instrument (MAUI), and can be used as inputs for cost-utility analyses and in clinical assessment. This research assessed associations of diet with subsequent HSU in a large international cohort of people living with multiple sclerosis (MS), a progressive autoimmune condition of the central nervous system. METHODS: HSUs were generated from responses to Short-Form Six-Dimension (SF-6D) MAUI, and quality-of-the-diet by Diet Habits Questionnaire (DHQ). Cross-sectional, and short- and long-term prospective associations of DHQ with HSU evaluated by linear regression at 2.5- and 5-years. Pooled prospective associations between DHQ and HSU evaluated using linear and quantile regression. Analyses adjusted for relevant demographic and clinical covariates. RESULTS: Among 839 participants, baseline DHQ scores showed short- and long-term associations with subsequent HSU, each 10-unit increase in total DHQ score associated with 0.008-0.012 higher HSU (out of 1.00). These associations were dose-dependent, those in the top two quartiles of baseline DHQ scores having 0.01-0.03 higher HSU at follow-up, 0.03 being the threshold for a minimally clinically important difference. Fat, fiber, and fruit/vegetable DHQ subscores were most strongly and consistently associated with better HSU outcomes. However, baseline meat and dairy consumption were associated with 0.01-0.02 lower HSU at subsequent follow-up. CONCLUSIONS: A higher quality-of-the-diet showed robust prospective relationships with higher HSUs 2.5- and 5-years later, substantiating previous cross-sectional relationships in this cohort. Subject to replication, these results suggest interventions to improve the quality-of-the-diet may be effective to improve HRQoL in people living with MS.

A repeated cross-sectional and longitudinal study of mental health and wellbeing during COVID-19 lockdowns in Victoria, Australia.

BACKGROUND: Population surveys across the world have examined the impact of the COVID-19 pandemic on mental health. However, few have simultaneously examined independent cross-sectional data with longitudinal data, each of which have different strengths and weaknesses and facilitate the investigation of distinct research questions. This study aimed to investigate psychological distress and life satisfaction during the first and second lockdowns in the state of Victoria, Australia, and the social factors that may be affected by lockdowns and could affect mental health. METHODS: The VicHealth Victorian Coronavirus Wellbeing Impact Study included two 20-min opt-in online panel surveys conducted in May and September 2020 in Victoria, each with a sample of 2000 adults aged 18 + . A two-part study design was used: a repeated cross-sectional study of respondents who participated in Survey One and Survey Two, followed by a longitudinal nested cohort study. The primary exposures were social solidarity, social connectedness and staying connected with family and friends. Using logistic regression modelling, we explored the associations between our exposures and primary outcomes of psychological distress and life satisfaction with and without adjustment for covariates, both cross-sectionally and longitudinally. The results from the multivariable models were summarised using adjusted Odds Ratios (aOR), 95% Confidence Intervals (CI). RESULTS: Cross-sectional results indicated that the percentage of participants with low life satisfaction was significantly higher in the second survey sample (53%) compared to the first (47%). The percentage of participants with high psychological distress was higher but not significantly different between the two survey samples (14% first survey vs 16% second survey). Longitudinal study results indicated that lower social connectedness was significantly associated with higher psychological distress (aOR:3.3; 95% CI: 1.3-8.4) and lower life satisfaction (aOR:0.2; 95% CI: 0.1-0.4). Younger adults had higher psychological distress compared to older adults (aOR:6.8; 95% CI:1.5-31.1). Unemployment at the time of the first survey was significantly associated with lower life satisfaction at the second survey (aOR:0.5; 95% CI: 0.3-0.9). CONCLUSION: This study supports the findings of other international studies. It also highlights the need to promote increased social connection and maintain it at times of isolation and separation, particularly amongst younger adults.

RUV-III-NB: normalization of single cell RNA-seq data.

Normalization of single cell RNA-seq data remains a challenging task. The performance of different methods can vary greatly between datasets when unwanted factors and biology are associated. Most normalization methods also only remove the effects of unwanted variation for the cell embedding but not from gene-level data typically used for differential expression (DE) analysis to identify marker genes. We propose RUV-III-NB, a method that can be used to remove unwanted variation from both the cell embedding and gene-level counts. Using pseudo-replicates, RUV-III-NB explicitly takes into account potential association with biology when removing unwanted variation. The method can be used for both UMI or read counts and returns adjusted counts that can be used for downstream analyses such as clustering, DE and pseudotime analyses. Using published datasets with different technological platforms, kinds of biology and levels of association between biology and unwanted variation, we show that RUV-III-NB manages to remove library size and batch effects, strengthen biological signals, improve DE analyses, and lead to results exhibiting greater concordance with independent datasets of the same kind. The performance of RUV-III-NB is consistent and is not sensitive to the number of factors assumed to contribute to the unwanted variation.

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.

Viability of a MSQOL-54 general health-related quality of life score using bifactor model.

BACKGROUND: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated. METHODS: A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical). RESULTS: The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70). CONCLUSIONS: The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score.

Two healthy lifestyle scores are associated with lower subsequent fatigue risk using inverse probability weighting in an international longitudinal cohort of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Several modifiable lifestyle factors have been associated with the onset and health outcomes of multiple sclerosis (MS), including clinically significant fatigue. A combined lifestyle score approach represents one method of assessing their relationship with clinical outcomes. The aim was to examine the association of two lifestyle scores with clinically significant fatigue and change thereof over 2.5 years' follow-up using inverse probability treatment weighting (IPTW). METHODS: Data on sociodemographic, lifestyle, and clinical characteristics surveyed from an international cohort of people with MS at baseline and at 2.5-year follow-up were used. Fatigue was defined by the Fatigue Severity Scale (FSS >5) and healthy lifestyle by the Healthy Lifestyle Index Score (HLIS) and the Smoking, Nutrition, Alcohol Consumption and Physical Activity (SNAP) score. Analyses were by IPTW accounting for age, sex, MS type, disability, treated comorbidity number, immunomodulatory medication use, prescription antifatigue medication use, and ongoing relapse symptoms. RESULTS: In total, 1268 participants completed the FSS at both time points; approximately 62% had fatigue. Using doubly robust IPTW, high (>11/20) HLIS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.81-0.98) and high (>3/5) SNAP (OR 0.82, 95% CI 0.73-0.90) were each associated with lower risk of fatigue at follow-up. Evaluating change in fatigue, a higher SNAP score was associated with a lower risk of fatigue (OR 0.89, 95% CI 0.80-0.97) but the score for HLIS did not reach statistical significance (OR 0.93, 95% CI 0.85-1.01). CONCLUSION: These results suggest a robust role for key lifestyle factors in preventing clinically significant fatigue and may represent a place for lifestyle modification in improving clinical outcomes in MS.

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.

Depression mediates the relationship between fatigue and mental health-related quality of life in multiple sclerosis.

BACKGROUND: Fatigue is among the most prevalent symptoms for people with multiple sclerosis (pwMS) and is significantly detrimental to mental health-related (mental) quality of life (QoL). We examined the role of depression and physical activity as mediators in the fatigue-QoL relationship in pwMS. METHODS: Using baseline cross-sectional data from an international cohort of 2,104 pwMS, characteristics of fatigue and mental QoL, measured by Fatigue Severity Scale and MSQOL-54 respectively, were assessed using linear and log-binomial regression. Structural Equation Models (SEM) were used to explore the mediating roles of depression and physical activity between fatigue and mental QoL. RESULTS: The median mental QoL score was 71.9/100. The mean fatigue score was 41.5/63, with 65.6% participants having clinically significant fatigue. In the SEM evaluating depression as a mediator of the fatigue-QoL relationship, mental QoL was 14.72 points lower (95% CI: -16.43 -13.01, p<0.001) in participants with clinically significant fatigue, of which depression accounted for 53.0% (-7.80, 95% CI: -9.03 -6.57, p<0.001). In the SEM evaluating physical activity as a mediator of the fatigue-QoL relationship, mental QoL was 10.89 points lower (95% CI: -12.47, -9.32, p<0.001) in participants with clinically significant fatigue, of which the indirect effect via physical activity accounted for only 4.4% (-0.48, 95% CI: -0.81, -0.14, p=0.005). CONCLUSION: Depression accounted for the majority of the fatigue-mental QoL relationship when modelled as a mediator, while physical activity had only a minor role. Our findings may inform the development of treatments for reducing the impacts of fatigue and improving mental QoL in pwMS.

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.

Perceived cognitive impairment is associated with sexual dysfunction in people with multiple sclerosis: A 2.5-year follow-up study of a large international cohort.

BACKGROUND: The potential relationship between perceived cognitive impairment (PCI) and sexual dysfunction in multiple sclerosis (MS) has not been studied. OBJECTIVES: To explore the relationship between cognitive impairment and sexual dysfunction over 2.5 years in people with MS. METHODS: Data were derived from the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) international cohort over 2.5 years' follow-up. Cognitive function and sexual function were assessed by sub-scores of the MS Quality of Life-54. The impact of perceived cognitive impairment on sexual dysfunction was assessed by calculating prevalence ratios (PR) and relative risks (RR) with 95% confidence intervals (CI) using log-binomial regression models. RESULTS: 1958 participants were included at baseline, of whom 555 without perceived cognitive impairment at baseline comprised the longitudinal cohort. The prevalence of perceived cognitive impairment at baseline was 45.6%. At baseline, cognitive impairment was associated with increased frequency of self-reported sexual dysfunction (aPR=1.32, 95% CI: 1.17-1.48). Among the sample without sexual dysfunction at baseline, incident sexual dysfunction was more common among participants with persistent (aRR=1.61, 95% CI: 1.06-3.18) and newly reported cognitive impairment (aRR=1.89, 95% CI: 1.14-3.14). CONCLUSION: Results suggest PCI may be an independent risk factor for sexual dysfunction in PwMS, which may represent an additional dimension whereby MS may adversely affect quality of life.

Therapeutic utilization of meditation resources by people with multiple sclerosis: insights from an online patient discussion forum.

We aimed to describe website traffic and qualitatively analyze an e-health community discussion forum. Participants in this study were people affected by multiple sclerosis visiting the Overcoming Multiple Sclerosis (OMS) website. This mixed methods study combined descriptive analysis of website traffic over 7 years and 1 month, and qualitative analysis of 1 week of posts in the meditation topic, coded into theme groups using qualitative thematic analysis. There were 166 meditation topics posted with 21,530 initial views of primary post and 785 sub-post responses. Meditation posts and sub-posts received 368,713 replies. Number of views increased from 4,684 in 2011 to over 80,000 in 2017, a considerably greater rate of increase than overall traffic. Qualitative analysis of posts on the meditation forum identified themes of barriers and enablers to utilization of meditation resources. Enablement themes dominated, observed across six of the seven theme groups with various forms of positive social and emotional support to learn and practice meditation. One theme, negative emotion, was identified as a barrier. The OMS peer-to-peer patient online discussion forum serves important functions in encouraging, educating and enabling its growing online community. Our analysis may help improve and innovate online support for lifestyle management in many chronic diseases.