The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the ...anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk.
Social needs interventions in medical settings aim to mitigate the effects of adverse social circumstances on health outcomes by connecting vulnerable patients with resources. This study examined the ...relationship between intervention dosage and the success of resource connections using data from a social needs intervention in multiple clinical settings across the US.
The intervention uses a case management approach to connect patients with unmet needs to resources and services in the community. Intervention dosage was conceptualized as the number of contacts between the navigator and the patient, categorized as direct contact (phone vs. in person) and indirect contact (initiated by the navigator vs. patient). Success of the intervention was conceptualized as ‘none,’ ‘partial,’ or ‘optimal’ for each patient, based on the number of social needs the resource connections addressed.
Administrative data were extracted for 38,404 unique patients who screened positive for unmet resource needs between 2012 and 2017. Owing to the large sample size, statistical corrections were made to reduce type I error.
Multinomial logistic regression analyses showed that higher intervention dosage was related to greater success of resource connections, after adjusting for the patient and site characteristics, and the number of needs (odds ratios ranged from 1.62 to 2.89). In-person contact, although received by only 25% of the patients, was associated with the highest probability of optimal success.
This study demonstrates a feasible way to conceptualize an intervention dose for a social needs intervention that uses a case management approach and has implications for how intervention delivery may improve success of resource connections.
•There is a dose-response relationship between amount of intervention and resource connection outcomes, after controlling for patient sociodemographic and contextual characteristics.•Higher dose of intervention over the phone leads to a few successful outcomes and a higher dose in person leads to optimal success outcomes.•Patient sociodemographics did not relate consistently or strongly to intervention dosage.•Patients originating as walk-ups when they had signed up for the intervention received a higher dosage of in-person intervention compared with those who arrived at the site indirectly.
Summary Background Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of ...lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. Methods The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. Findings Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ2 on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40–1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. Interpretation We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. Funding The Motor Neurone Disease Association of Great Britain and Northern Ireland.
Abstract
The study was aimed at evaluating the effect of supplementing a diet for laying hens with onion and garlic extracts on their productive performance and egg quality. Two-hundred-sixteen ...laying hens were divided into 3 groups: standard diet, diet with a 0.0032% addition of onion extract, and diet with a 0.0032% addition of garlic extract. The egg production rate, egg weight, and feed conversion ratio were monitored within the first 17 wk of the laying period. In wk 6, 8, 10, 12, 14, and 16 of the laying period, eggs were analyzed for: weight, weight to yolk ratio, yolk color, albumen quality, and eggshell quality. In wk 7 and 15 of the laying period, analyses were conducted for: yolk color, consistency, aroma, and taste of boiled eggs. The addition of a garlic extract had a positive effect on the production rate in the initial and peak egg-laying period, and significantly determined the aroma and, in the further stage of the production process, also taste of boiled eggs. Administration of the diet with onion extract to hens caused them to begin the egg-laying period later but laying heavier eggs, with a higher content of egg yolk and better quality of albumen. The analysis of the productive performance of hens and quality of eggs indicates the advisability of applying the extract from garlic in commercial flocks of laying hens. In the future, it seems substantiated to analyze the effect of extract supplementation at the end of the laying period.
•People with MS mostly utilise a mix of active problem- and emotion-focused coping strategies.•Older age, presence of a partner and shorter disease duration associated with adaptive ...strategies.•Younger age, being male and having RRMS are associated with higher substance use.•Being female associated with greater use of emotion-focused strategies.•Unemployment and greater disability associated with higher use of avoidance strategies.
Coping positively and negatively influences psychosocial and other outcomes in multiple sclerosis (MS), but there is conflicting evidence about the use of different coping strategies and their associations with demographic and disease characteristics. Our aims were to examine which coping strategies are used by a large sample of people with MS, then to identify any associations between demographic and disease related factors with use of individual coping strategies.
Participants in the Trajectories of Outcomes in Neurological Conditions (TONiC) study completed the Coping Orientations to Problems Experienced (COPE60) questionnaire. Relationships between demographic and clinical characteristics and coping strategies were examined by multiple ordinal logistic regression to assess the effect of each potential predictor after adjustment for other possible covariates.
From 722 patients, the most commonly used strategy was Acceptance, followed by Active Coping, Planning and Positive Reinterpretation and Growth. All but two strategies showed significant associations with demographic and clinical characteristics. The most marked effects were found for Restraint, with people in employment 2.1 times as likely to utilise this strategy compared to those unemployed, and Seeking of Emotional Social Support and Focus on and Venting of Emotions, which were utilised twice as much by women compared to men. Behavioural and Mental Disengagement were highly associated with greater disability and not being in employment.
Clinicians should be aware of several disease and demographic characteristics that are associated with use of potentially maladaptive coping strategies.
Central pain in multiple sclerosis (MS) is common and often refractory to treatment.
We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, ...placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours.
Sixty-four patients (97%) completed the trial, 34 received CBM. In week 4, the mean number of daily sprays taken of CBM (n = 32) was 9.6 (range 2 to 25, SD = 6.0) and of placebo (n = 31) was 19.1 (range 1 to 47, SD = 12.9). Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale. CBM was superior to placebo in reducing the mean intensity of pain (CBM mean change -2.7, 95% CI: -3.4 to -2.0, placebo -1.4 95% CI: -2.0 to -0.8, comparison between groups, p = 0.005) and sleep disturbance (CBM mean change -2.5, 95% CI: -3.4 to -1.7, placebo -0.8, 95% CI: -1.5 to -0.1, comparison between groups, p = 0.003). CBM was generally well tolerated, although more patients on CBM than placebo reported dizziness, dry mouth, and somnolence. Cognitive side effects were limited to long-term memory storage.
Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated.
•Validation of a self declared MS Population with a clinically diagnosed one.•We analysed the UK MS Register for a number of key characteristics. The internet (n = 11,021) and clinical (n = 3,003) ...populations were studied for key shared epidemiology. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2)•There is a representative population of people with MS in the online element of the UK MS Register – The MS Register can be utilised as a valid cohort for Clinical and PRO research•Kernel Density of the populations for age can be seen in the graphs:
The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture ‘real world’ information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients.
A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the ‘linked dataset’. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data.
The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution.
Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.
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Background:
Sexual dysfunction (SD) is common among people with multiple sclerosis, but there is limited information on its relationships.
Objective:
This national study examines the relationships ...between sexual function with demographic factors, physical function, fatigue and depression.
Methods:
Participants in the Trajectories of Outcomes in Neurological Conditions (TONiC) study completed the measures of fatigue, physical function and depression together with the Multiple Sclerosis Intimacy and Sexuality Questionnaire-15 (MSISQ-15), which covers sexual function (primary), symptoms that interfere with sexual function (secondary) and psychological issues (tertiary). All ordinal scores from the measures were converted to interval scale latent estimates via the Rasch model and used as single indicator latent variables in path analysis.
Results:
From 722 patients, 538 were sexually active of whom 431 (80.1%) answered questions on sexual functioning. Of these, only 18.5% reported no impact on any aspect of sexual function. Dysfunction was linked to disease subtype and Expanded Disability Status Scale (EDSS). Subtype influenced the relationship between symptoms and sexual function, which was fully mediated by psychological factors in secondary progressive patients. Depression was not directly associated with sexual functioning, but appeared as a consequence of the psychological issues associated with SD.
Conclusion:
SD is common among participants in this UK-wide study, and psychological aspects of SD contributed to depression.
Alemtuzumab and chronic plaque psoriasis Aslam, A.; Marsland, A.M.; Rog, D. ...
British journal of dermatology (1951),
July 2013, Letnik:
169, Številka:
1
Journal Article
Age prediction from DNA has been a topic of interest in recent years due to the promising results obtained when using epigenetic markers. Since DNA methylation gradually changes across the ...individual’s lifetime, prediction models have been developed accordingly for age estimation. The tissue-dependence for this biomarker usually necessitates the development of tissue-specific age prediction models, in this way, multiple models for age inference have been constructed for the most commonly encountered forensic tissues (blood, oral mucosa, semen). The analysis of skeletal remains has also been attempted and prediction models for bone have now been reported. Recently, the VISAGE Enhanced Tool was developed for the simultaneous DNA methylation analysis of 8 age-correlated loci using targeted high-throughput sequencing. It has been shown that this method is compatible with epigenetic age estimation models for blood, buccal cells, and bone. Since when dealing with decomposed cadavers or postmortem samples, cartilage samples are also an important biological source, an age prediction model for cartilage has been generated in the present study based on methylation data collected using the VISAGE Enhanced Tool. In this way, we have developed a forensic cartilage age prediction model using a training set composed of 109 samples (19–74 age range) based on DNA methylation levels from three CpGs in FHL2, TRIM59 and KLF14, using multivariate quantile regression which provides a mean absolute error (MAE) of ± 4.41 years. An independent testing set composed of 72 samples (19–75 age range) was also analyzed and provided an MAE of ± 4.26 years. In addition, we demonstrate that the 8 VISAGE markers, comprising EDARADD, TRIM59, ELOVL2, MIR29B2CHG, PDE4C, ASPA, FHL2 and KLF14, can be used as tissue prediction markers which provide reliable blood, buccal cells, bone, and cartilage differentiation using a developed multinomial logistic regression model. A training set composed of 392 samples (n = 87 blood, n = 86 buccal cells, n = 110 bone and n = 109 cartilage) was used for building the model (correct classifications: 98.72%, sensitivity: 0.988, specificity: 0.996) and validation was performed using a testing set composed of 192 samples (n = 38 blood, n = 36 buccal cells, n = 46 bone and n = 72 cartilage) showing similar predictive success to the training set (correct classifications: 97.4%, sensitivity: 0.968, specificity: 0.991). By developing both a new cartilage age model and a tissue differentiation model, our study significantly expands the use of the VISAGE Enhanced Tool while increasing the amount of DNA methylation-based information obtained from a single sample and a single forensic laboratory analysis. Both models have been placed in the open-access Snipper forensic classification website.
•New age prediction model for cartilage samples developed using the VISAGE Enhanced Tool assay and quantile regression.•DNA methylation levels in three CpG sites analyzed using MiSeq on cartilage led to MAE of ± 4.26 years.•Novel tissue prediction model for somatic cells using the VISAGE Enhanced Tool assay and multinomial logistic regression.•DNA methylation levels in eight CpGs on blood, buccal cells, bone and cartilage predicted 97.4% correct tissue of origin.
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