Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. OBJECTIVES: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. STUDY SELECTION: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. STUDY APPRAISAL: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. RESULTS: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. LIMITATIONS: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. CONCLUSIONS: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013953. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

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.

Oil tea improves glucose and lipid levels and alters gut microbiota in type 2 diabetic mice.

Oil tea has traditionally been used in minority populations in China for treating various ailments in traditional Chinese medicine. Individually, green tea and ginger, which are the main ingredients of oil tea, have demonstrated antidiabetic effects; however, whether oil tea exerts antidiabetic effects remains unknown. In addition, aberrant gut microbiota structure is associated with diabetic status, and research indicates that there may be beneficial effects of tea on gut microbiota. Therefore, we hypothesized that oil tea exerts antidiabetic effects and induces alteration in gut microbiota. To test our hypothesis, we first examined the nutrition composition of oil tea. Then, db/db mice were randomly divided into 3 groups and orally gavaged with saline, metformin, and oil tea for 8 weeks. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and lipid levels were tested during the experiment. 16S rRNA genes were sequenced and changes in gut microbiota in response pre/post treatment were examined. Our experiments showed that oil tea contains high concentrations of tea polyphenols (246.35 mg/100 g) and [6]-gingerol (2.98 mg/100 g). It appeared that oil tea treatment significantly suppressed the postprandial blood glucose elevation and lowered the levels of FBG, total cholesterol, triglycerides, and LDL-cholesterol (P < .05). The composition of gut microbiota changed significantly in response to oil tea treatment, Lachnospiraceae were significantly enriched (q < 0.05, LDA score> 3.5). Redundancy analysis identified 155 oil tea-modulating family level phylotypes, where Lachnospiraceae significantly correlated with FBG, total cholesterol, and LDL-cholesterol (P < .05). Our findings demonstrate that oil tea improved glucose and lipid levels and modulated gut microbiota in db/db mice.

Sun Exposure across the Life Course Significantly Modulates Early Multiple Sclerosis Clinical Course.

BACKGROUND: Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. OBJECTIVES: To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). METHODS: Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. RESULTS: Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. CONCLUSION: We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

The Role of Vitamin D in Multiple Sclerosis: Biology and Biochemistry, Epidemiology and Potential Roles in Treatment.

BACKGROUND: Multiple sclerosis (MS) is a progressive, demyelinating condition of the central nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function. Of the various environmental and behavioural risk factors identified as playing a role in MS onset and progression, perhaps none has been as consistent as vitamin D. OBJECTIVE: In this review, we will endeavour to present a general background on the role of vitamin D in human health and particularly in MS, as well as the substantial epidemiological evidence in support of vitamin D's role in MS. RESULTS: Initially identified via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin D has since been demonstrated to have a strong and consistent inverse association with MS risk and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25- hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have lower levels of 25(OH)D than other cases with less active disease. These case-control and crosssectional study results led the way to cohort studies which indicated significant inverse associations between serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational evidence have been the impetus for completed and ongoing randomised trials of vitamin D supplementation, alone or in addition to standard immunomodulatory medications, as an intervention in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin D has been demonstrated to interact with a variety of other risk factors, from genetic predictors like HLA-DR1 genotype to behavioural factors like smoking. CONCLUSION: There is an abundance of epidemiological evidence, both direct and indirect, as well as significant biological plausibility substantiating a role for vitamin D in the onset and progression of multiple sclerosis.

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.

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

A novel method for calculating prevalence of multiple sclerosis in Australia.

OBJECTIVES: The purpose of this study was to determine the prevalence of multiple sclerosis (MS) in Australia in 2010 using a novel method based on Australia-wide prescription data for MS-specific disease modifying agents. The results obtained were validated against two other prevalence estimates. METHODS: We obtained the total number of scripts for medications that were used exclusively for the treatment of MS written in Australia for the period January-December 2010. The percentage of MS patients using medications (42-55%) was taken from state-specific surveys of MS Society clients. To estimate prevalence we divided the annual number of scripts dispensed by 12 and adjusted for penetration of medications by state. RESULTS: The prevalence of MS in Australia in 2010 calculated using the prescription method was 21,283 people (95.5/100,000). This compared to 21,200 people (95.2/100,000) obtained from the Australian Bureau of Statistics (ABS) Survey of Disability, Ageing and Carers (SDAC) survey of 2009 and 20,471 people (91.9/100,000) using MS Society client numbers. Prevalence increased with increasing latitude, with the prevalence for Tasmania over seven times that of the Northern Territory. Results were sensitive to the percentage of people with MS being treated. CONCLUSIONS: Calculation of prevalence of MS using nation-wide prescription data is a novel method that generates results similar to other potentially more resource-intensive methods.

Recruitment and retention of palliative cancer patients and their partners participating in a longitudinal evaluation of a psychosocial retreat program.

OBJECTIVE: The negative impact of a palliative cancer diagnosis on the quality of life of patients and their partners is well documented. Unfortunately, research on interventions to improve psychological and spiritual well-being of these couples has been considered impractical because of the deleterious influence of disease progression on participation. This study evaluated the feasibility of offering the Tapestry Retreat, an intensive psychosocial intervention for palliative care patients and their partners. METHODS: Participants in the Tapestry Retreat included 15 patients with advanced breast, prostate, or colon cancer and their partners (n = 30). Also included was a natural history group consisting of 20 patients and their partners (n = 40). All couples completed questionnaires related to quality of life, distress, marital satisfaction, and existential concerns at baseline, after the retreat or 1 month after baseline, and then again at 3, 6, 9, and 12 months. RESULTS: Patients in the Tapestry group were significantly more likely to be women who had received prior psychological support and were less comfortable with their finances. Partners attending the Tapestry retreat were also more likely to have received prior psychological support. SIGNIFICANCE OF RESULTS: Despite issues with recruitment and retention, retreat participation was considered feasible. Recommendations for future research are discussed.