Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials

Background

Low serum levels of 25-hydroxyvitamin D have been associated with worse outcomes in multiple sclerosis (MS) patients treated with interferon-beta. Association of vitamin D nutrition on the outcomes of other MS therapies has been studied less.

Objective

Whether patients in the phase 3 fingolimod trials using vitamin D supplements have better clinical, MRI and safety outcomes than non-users.

Materials and methods

Pooled data from phase 3 FREEDOMS trials was analyzed post hoc. Vitamin D use was defined as ‘non-users’ (n = 562), ‘casual users’ (n = 157) and ‘daily users’ (usage 100% time in the study, n = 110).

Results

Expanded Disability Status Scale change from baseline to month 24, and annual relapse rate and proportion of patients with relapses were similar across the vitamin D user groups. Proportion of patients free of new/enlarging T2 lesions significantly favored vitamin D ‘daily users’ versus ‘non-users’. Mean number of lesions were lower and proportion of patients free of gadolinium-enhanced T1-lesions were higher in the ‘daily users’. At month 12, percent brain volume change was significantly lower in the ‘daily users’ versus ‘non-users’ and remained low at month 24 (non-significant). Incidence of depression was lower for vitamin D ‘daily users’ (non-significant).

Conclusions

We observed improved MRI outcomes on percent brain volume change and proportion of patients free of new/enlarging T2 lesions, and a trend of less depression in the ‘daily users’ of vitamin D supplement in patients in the FREEDOMS trials.

     

Assessing the structure and meaningfulness of the dissociative subtype of PTSD

Purpose

Studies conducted in the USA, Canada and Denmark have supported the existence of the dissociative PTSD subtype, characterized primarily by symptoms of depersonalization and derealization. The current study aimed to examine the dissociative PTSD subtype in an Eastern European, predominantly female (83.16%) sample, using an extended set of dissociative symptoms.

Methods

A latent profile analysis was applied to the PTSD and dissociation data from 689 trauma-exposed university students from Slovakia.

Results

Four latent profiles of varying PTSD and dissociation symptomatology were uncovered. They were named non-symptomatic, moderate PTSD, high PTSD and dissociative PTSD. The dissociative PTSD profile showed elevations on depersonalization and derealization, but also the alternative dissociative indicators of gaps in awareness and memory, sensory misperceptions and cognitive and behavioural re-experiencing. The core PTSD symptoms of ‘memory impairment’ and ‘reckless or self-destructive behaviour’ were also significantly elevated in the dissociative PTSD profile. Moreover, anxiety and anger predicted membership in the dissociative PTSD profile.

Conclusion

The results provide support for the proposal that the dissociative PTSD subtype can be characterized by a variety of dissociative symptoms.

     

Delayed Deterioration of EEG Background Rhythm Post-cardiac Arrest

Background

Electroencephalogram (EEG) background continuity is associated with a favorable prognosis in cardiac arrest patients post-therapeutic hypothermia. However, the continuous EEG in a subset of patients will undergo ‘delayed EEG deterioration’; they will invariably have poor outcome. The aim of this study was to characterize this phenomenon.

Methods

We studied a prospectively collected cohort of consecutive cardiac arrest patients who underwent therapeutic hypothermia between July 2012 and May 2015. We identified patients with an initially favorable EEG rhythm post-cooling and characterized a subset of patients with delayed EEG deterioration.

Results

A total of 133 patients were included in the analysis. Of these, 69/133 (51.9%) had an initially favorable EEG. Of those patients with initially favorable EEG, 7/69 (10.1%) had a subsequent deterioration. Delayed EEG deterioration was associated with poor outcome. The median time to deterioration was 55 h.

Conclusions

Delayed EEG deterioration is associated with poor clinical outcomes. We hypothesize that this is the result of delayed neuronal degeneration, the exact mechanism requiring further exploration. Identifying patients with delayed EEG deterioration post-therapeutic hypothermia is paramount as further interventions may yet salvage their outcomes, though further study is needed.

     

What is the process by which a decision to administer electroconvulsive therapy (ECT) or not is made? A grounded theory informed study of the multi-disciplinary professionals involved

Purpose

To develop a grounded theory-informed model explaining the decision-making process professionals in multi-disciplinary teams go through in deciding whether to administer electroconvulsive therapy (ECT) or not.

Methods

A grounded theory informed methodology was used to analyse the data offered by ten participants who had all been involved in the process of deciding if someone has ECT or not.

Results

The core categories, described as ‘layers’ in this research, ‘personal and professional identity’; ‘subjective vs objective’; ‘Guidelines or Clinical Instinct?’; ‘Someone has to take Responsibility’ and ‘the decision in action’, were constructed from the data.

Conclusions

The study describes a useful insight into the layers of the decision-making process that could be further considered in clinical settings. The model highlights the decision to give ECT that has many different layers including professional identity, how a person understands the evidence base, past experiences, and the amount of power they have in the process. The consultant psychiatrist and the patient were seen as holding most power in the process depending on whether the Mental Capacity Act (2005) or Mental Health Act (2007) was being followed. Patients were seen to experience a very different decision-making process dependant on the personal views of the professionals in relation to ECT.

     

Is CT perfusion helpful in the treatment allocation of patients with acute ischemic stroke? An expert-opinion analysis

Background

Intravenous tPA is the standard treatment for acute ischemic stroke within 4.5 hours of symptom onset. Neuroradiological selection is currently based upon non-contrast- brain CT scan (NCCT).

Aims

To verify, in an “expert-opinion setting”, the possible usefulness of CT perfusion (CTP) in decision-making toward i.v. thrombolysis.

Patients and method

One hundred and three consecutive patients with acute ischemic stroke who underwent NCCT and CTP were re-evaluated by an expert in cerebrovascular disease, to verify if adding CTP information would have changed expert’s opinion.

Results

After CTP, a definitive decision was made for 20 more patients, changing the proportion of patients candidate to i.v. tPA from 44% to 51%, and reducing uncertainty from 29% to 10%. CTP results were useful inmilder stroke (p = 0.01).

Conclusions

In a “real world” setting, CT perfusion could be useful for clinical decision, in particular for milder stroke.

     

Psychological Determinants of Medication Adherence in Stroke Survivors: a Systematic Review of Observational Studies

Background

Medications targeting stroke risk factors have shown good efficacy, yet adherence is suboptimal. To improve adherence, its determinants must be understood. To date, no systematic review has mapped identified determinants into the Theoretical Domains Framework (TDF) in order to establish a more complete understanding of medication adherence.

Purpose

The aim of this study was to identify psychological determinants that most influence stroke survivors’ medication adherence.

Methods

In line with the prospectively registered protocol (PROSPERO CRD42015016222), five electronic databases were searched (1953–2015). Hand searches of included full text references were undertaken. Two reviewers conducted screening, data extraction and quality assessment. Determinants were mapped into the TDF.

Results

Of 32,825 articles, 12 fulfilled selection criteria (N = 43,984 stroke survivors). Tested determinants mapped into 8/14 TDF domains. Studies were too heterogeneous for meta-analysis. Three TDF domains appeared most influential. Negative emotions (‘Emotions’ domain) such as anxiety and concerns about medications (‘Beliefs about Consequences’ domain) were associated with reduced adherence. Increased adherence was associated with better knowledge of medications (‘Knowledge’ domain) and stronger beliefs about medication necessity (‘Beliefs about Consequences’ domain). Study quality varied, often lacking information on sample size calculations.

Conclusions

This review provides foundations for evidence-based intervention design by establishing psychological determinants most influential in stroke survivors’ medication adherence. Six TDF domains do not appear to have been tested, possibly representing gaps in research design. Future research should standardise and clearly report determinant and medication adherence measurement to facilitate meta-analysis. The range of determinants explored should be broadened to enable more complete understanding of stroke survivors’ medication adherence.

     

Asymptomatic Carotid Stenosis: Intervention or Best Medical Therapy?

Purpose of Review

Provide a current overview regarding the optimal strategy for managing patients with asymptomatic carotid artery stenosis.

Recent Findings

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce long-term stroke risk in asymptomatic patients. However, CAS is associated with a higher risk of peri-procedural stroke. Improvements in best medical therapy (BMT) have renewed uncertainty regarding the extent to which results from older randomised controlled trials (RCTs) comparing outcomes following carotid intervention can be generalised to modern medical practise.

Summary

‘Average surgical risk’ patients with an asymptomatic carotid artery stenosis of 60–99% and increased risk of late stroke should be considered for either CEA or CAS. In patients deemed ‘high risk’ for surgery, CAS is indicated. Use of an anti-platelet, anti-hypertensive and statin, with strict glycaemic control, is recommended. Results from ongoing large, multicentre RCTs comparing CEA, CAS and BMT will provide clarity regarding the optimal management of patients with asymptomatic carotid artery stenosis.

     

The network structure of paranoia in the general population

Purpose

Bebbington and colleagues’ influential study on ‘the structure of paranoia in the general population’ used data from the British National Psychiatric Morbidity Survey and latent variable analysis methods. Network analysis is a relatively new approach in psychopathology research that considers mental disorders to be emergent phenomena from causal interactions among symptoms. This study re-analysed the British National Psychiatric Morbidity Survey data using network analysis to examine the network structure of paranoia in the general population.

Methods

We used a Graphical Least Absolute Shrinkage and Selection Operator (glasso) method that estimated an optimal network structure based on the Extended Bayesian Information Criterion. Network sub-communities were identified by spinglass and EGA algorithms and centrality metrics were calculated per item and per sub-community.

Results

We replicated Bebbington’s four component structure of paranoia, identifying ‘interpersonal sensitivities’, ‘mistrust’, ‘ideas of reference’ and ‘ideas of persecution’ as sub-communities in the network. In line with previous experimental findings, worry was the most central item in the network. However, ‘mistrust’ and ‘ideas of reference’ were the most central sub-communities.

Conclusions

Rather than a strict hierarchy, we argue that the structure of paranoia is best thought of as a heterarchy, where the activation of high-centrality nodes and communities is most likely to lead to steady state paranoia. We also highlight the novel methodological approach used by this study: namely, using network analysis to re-examine a population structure of psychopathology previously identified by latent variable approaches.

     

Which cognitive dual-task walking causes most interference on the Timed Up and Go test in Parkinson’s disease: a controlled study

Background

There is evidence that cognitive load has a negative effect on the gait of patients with Parkinson’s disease (PD). However, it is not clear which type of cognitive activities are more likely to affect dual-task abilities in this patient group.

Aims

To compare the cognitive dual-task abilities in patients with PD and control subjects and to analyze the effect of different cognitive activities on the walking ability of patients with PD.

Methods

The Hoehn and Yahr scale, the Freezing of Gait Questionnaire (FOGQ), Montreal Cognitive Assessment (MoCA), and the Functional Reach Test were used to include and exclude the patients. The Timed Up and Go (TUG) test was applied under single and dual-task conditions.

Results

The completion time of TUG was found to be increased in the PD group compared with the healthy controls under single- and dual-task conditions (p?<?0.05). The completion time of TUG was significantly increased in dual-task conditions with complex attention activity (serial subtractions test) compared with other dual-task conditions in patients with PD (p?<?0.001).

Discussion

The gait performance of both healthy subjects and patients with PD was impaired with cognitive activity during walking, and patients with PD showed more impairment under different cognitive dual tasks. Among the other cognitive tasks, the ‘serial sevens’ test, a measure of complex attention, significantly increased the completion time of TUG.

Conclusions

While assessing the dual-task ability of patients with early-stage PD, tasks that increase the demand for complex attention seem to be more sensitive to showing impaired dual-task ability.

     

A life less lonely: the state of the art in interventions to reduce loneliness in people with mental health problems

Purpose

There is growing evidence of significant harmful effects of loneliness. Relatively little work has focused on how best to reduce loneliness in people with mental health problems. We aim to present an overview of the current state of the art in loneliness interventions in people with mental health problems, identify relevant challenges, and highlight priorities for future research and implementation.

Methods

A scoping review of the published and grey literature was conducted, as well as discussions with relevant experts, to propose a broad classification system for types of interventions targeting loneliness.

Results

We categorised interventions as ‘direct’, targeting loneliness and related concepts in social relationships, and ‘indirect’ broader approaches to well-being that may impact on loneliness. We describe four broad groups of direct interventions: changing cognitions; social skills training and psychoeducation; supported socialisation or having a ‘socially-focused supporter’; and ‘wider community approaches’. The most promising emerging evidence appears to be in ‘changing cognitions’, but, as yet, no approaches have a robust evidence base. Challenges include who is best placed to offer the intervention, how to test such complex interventions, and the stigma surrounding loneliness.

Conclusions

Development of clearly defined loneliness interventions, high-quality trials of effectiveness, and identifying which approaches work best for whom is required. Promising future approaches may include wider community initiatives and social prescribing. It is important to place loneliness and social relationships high on the wider public mental health and research agenda.

     

Subjective and objective measures of function and return to work: an observational study with a clinical psychiatric cohort

Purpose

To evaluate the association between two measurement tools (Social and Occupational Functioning Assessment Scale, SOFAS and Sheehan Disability Scale, SDS), returning to work (RTW) and their inter-correlation.

Methods

132 psychiatric patients referred to assessment of work ability participated. The association between SOFAS and SDS Work to RTW were assessed by logistic regression. Inter-correlations between SOFAS and SDS were assessed with the Spearman’s rho correlation coefficient.

Results

SOFAS and SDS Work scores were associated with a 1-year RTW and SOFAS and SDS were inter-correlated.

Conclusions

When assigning the ability to work, both subjective and objective measures of function predict RTW.

     

Onset of bladder and motor symptoms in multiple system atrophy: differences according to phenotype

Purpose

To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.

Methods

Medical records were retrospectively reviewed in 144 patients.

Results

Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).

Conclusions

Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.

     

Perceptions of Neighborhood Park Quality: Associations with Physical Activity and Body Mass Index

Background

Parks are important resources for physical activity (PA), yet few studies have examined how perceptions of park characteristics relate to PA and health.

Purpose

This study investigated associations between perceptions of neighborhood park quality and overall moderate-to-vigorous PA (MVPA), park-based PA, and body mass index (BMI).

Methods

Data were collected via questionnaire from 893 households in Kansas City, Missouri.

Results

The newly developed neighborhood park quality scale demonstrated good test–retest and internal reliability. Residents’ perceptions of neighborhood park quality were related to PA and health outcomes. Perceiving parks as a benefit was positively related to overall MVPA and park-based PA and negatively related to BMI. Perceptions of well-used parks were positively related to BMI, while perceived cleanliness was negatively related to park-based PA.

Conclusions

Better measuring and understanding how perceptions of local parks are associated with PA and health can improve appreciation of how parks facilitate active living.

     

Idiopathisch generalisierte Epilepsien

Background

Although the sociomedical importance of epilepsies has been extensively investigated, data regarding social long-term outcome and quality of life of people with idiopathic generalized epilepsies (IGE) are lacking.

Objectives

Predictors for the psychosocial outcome and the quality of life in patients with IGE are identified and discussed.

Materials and methods

The findings of existing studies on the social outcome in patients with various IGE syndromes are analyzed and discussed.

Results

Patients with absence epilepsy or juvenile myoclonic epilepsy (JME) are reported to have an unfavorable psychosocial outcome. While in JME a lower seizure frequency or remission of the epilepsy correlates with a favorable psychosocial outcome and a higher quality of life, remission of epilepsy is not predictive for a better social outcome among patients with absence epilepsy. Compared to other IGE syndromes, IGE with generalized, tonic–clonic seizures on awakening appears have a more favorable psychosocial outcome.

Conclusion

Several predictors for the psychosocial outcome and the quality of life have been identified and may potentially increase the clinicians’ ability and confidence to recommend different treatment options to patients with IGE.

     

Physician Power to Declare Death by Neurologic Criteria Threatened

Background

Three recent lawsuits that address declaration of brain death (BD) garnered significant media attention and threaten to limit physician power to declare BD.

Methods

We discuss these cases and their consequences including: the right to refuse an apnea test, accepted medical standards for declaration of BD, and the irreversibility of BD.

Results

These cases warrant discussion because they threaten to: limit physicians’ power to determine death; incite families to seek injunctions to continue organ support after BD; and force hospitals to dispense valuable resources to dead patients in lieu of patients with reparable illnesses or injuries.

Conclusions

Physicians, philosophers, religious officials, ethicists, and lawyers must work together to address these issues and educate both the public and medical community about BD.

     

Homeless women with schizophrenia reported lower adherence to their medication than men: results from the French Housing First experience

Objective

The aim of this study was to investigate the factors associated with non-adherence to medication in a large multi-center sample of homeless schizophrenia (HSZ) patients.

Methods

This multi-center study was conducted in four French cities: Lille, Marseille, Paris, and Toulouse. In addition to the Medication Adherence Rating Scale (MARS), sociodemographic information, history of homelessness, illness severity using the Modified Colorado Symptom Index (MCSI) and the Multnomah Community Integration Scale (MCAS), and drug information were collected.

Results

In total, 218 HSZ patients (16.1% women, mean age 36.8 ± 9.3 years) were included in this study. In the multivariate analysis, being a woman and having higher illness severity (MCSI score) and lower “acceptance of illness” (MCAS score) were significantly associated with lower MARS index scores. Compared to men, women had lower MARS dimension 1 (‘medication adherence behavior’) and dimension 3 (‘negative side effects and attitudes toward psychotropic medication’) scores. First-generation antipsychotic use was also associated with lower MARS dimension 3 scores.

Conclusion

HSZ women reported lower adherence than men, mainly due to having more subjective negative side effects and worse attitudes toward psychotropic medication. Future longitudinal studies should confirm these findings and explore the applicability of specific pharmacological and non-pharmacological treatment strategies for HSZ women, including treatment dose adaptation and psychoeducation. Clinical trial number NCT01570712.

     

Clinical Relevance of Steroid Use in Neuro-Oncology

Background

Corticosteroids are commonly used in the management of primary central nervous system (CNS) tumors and CNS metastases to treat cancer- and treatment-related cerebral edema and improve neurologic function. However, they are also associated with significant morbidity and mortality, given their wide range of adverse effects.

Purpose of Review

To review the mechanism of action, pharmacology, and toxicity profile of corticosteroids and to critically appraise the evidence that supports their use in neuro-oncologic practice based on the latest scientific and clinical data.

Recent Findings

Recent data suggest that corticosteroids may negatively impact survival in glioma patients. In addition, corticosteroids should be incorporated as a standard criterion to assess a patient’s clinical and radiographic response to treatment.

Summary

Corticosteroids should be used judiciously in neuro-oncologic patients, given the potential deleterious effects on clinical outcome and patient survival. Anti-angiogenic agents, which lack these adverse effects, may be a reasonable alternative to corticosteroids.