Non-invasive brain stimulation techniques for chronic pain

Copyright © 2014 The Cochrane Collaboration.Various devices are available that can electrically stimulate the brain without the need for surgery or any invasive treatment in order to manage chronic pain. There are four main treatment types: repetitive transcranial magnetic stimulation (rTMS) in which the brain is stimulated by a coil applied to the scalp, cranial electrotherapy stimulation (CES) in which electrodes are clipped to the ears or applied to the scalp, transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE) in which electrodes are applied to the scalp. These have been used to try to reduce pain by aiming to alter the activity of the brain, but the efficacy of these treatments is uncertain. This review update included 56 studies: 30 of rTMS, 11 of CES, 14 of tDCS and one of RINCE. We judged only three studies as having a low risk of bias. Low or very low-quality evidence suggests that low-frequency rTMS and rTMS applied to pre-frontal areas of the brain are not effective but that a single dose of high-frequency stimulation of the motor cortex area of the brain provides short-term pain relief. This effect appears to be small and may be exaggerated by a number of sources of bias. Studies that gave a course of multiple treatments of rTMS produced conflicting results with no overall effect seen when we pooled the results of these studies. Most studies of rTMS are small and there is substantial variation between studies in terms of the treatment methods used. Low-quality evidence does not suggest that CES or tDCS are effective treatments for chronic pain. A single small study of RINCE provided very low-quality evidence of a short-term effect on pain. For all forms of stimulation the evidence is not conclusive and uncertainty remains. The reporting of side effects varied across the studies. Of the studies that clearly reported side effects, short-lived and minor side effects such as headache, nausea and skin irritation were usually reported both after real and sham stimulation. There were two reports of seizure following real rTMS. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation. Previous readers should re-read this update. More studies of rigorous design and adequate size are required to evaluate accurately all forms of non-invasive brain stimulation for the treatment of chronic pain

Diminishing Return for Increased Mappability with Longer Sequencing Reads: Implications of the k-mer Distributions in the Human Genome

The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a greater length increases the chance for reads being uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the k-mer distribution of the human reference genome. The k-mer frequency is determined for k ranging from 20 to 1000 basepairs. We use the proportion of non-singleton k-mers to evaluate the mappability of reads for a corresponding read length. We observe that the proportion of non-singletons decreases slowly with increasing k, and can be fitted by piecewise power-law functions with different exponents at different k ranges. A faster decay at smaller values for k indicates more limited gains for read lengths > 200 basepairs. The frequency distributions of k-mers exhibit long tails in a power-law-like trend, and rank frequency plots exhibit a concave Zipf's curve. The location of the most frequent 1000-mers comprises 172 kilobase-ranged regions, including four large stretches on chromosomes 1 and X, containing genes with biomedical implications. Even the read length 1000 would be insufficient to reliably sequence these specific regions.Comment: 5 figure

Rehabilitation interventions for improving balance following stroke: an overview of systematic reviews

Background The aim of this study was to synthesize evidence from systematic reviews, to summarise the effects of rehabilitation interventions for improving balance in stroke survivors. Methods We conducted an overview of systematic reviews (SRs). We included Cochrane Systematic Reviews and non-Cochrane Systematic Reviews of randomized-controlled clinical trials and not-randomized clinical trials, in all types of stroke, comparing the effects of interventions, control interventions and no interventions on balance-related outcomes. We conducted a comprehensive search of electronic databases, from inception to December 2017. Data extracted included: number and type of participants, type of intervention, control intervention, method of assessing risk of bias of primary studies, balance outcome measures and results of statistical meta-analyses. Methodological quality of included reviews was assessed using AMSTAR 2. A narrative description of the characteristics of the SRs was provided and results of meta-analyses summarised with reference to their methodological quality. Results 51 SRs (248 primary studies and 10,638 participants) met the inclusion criteria and were included in the overview. All participants were adults with stroke. A wide variety of different balance and postural control outcomes were included. 61% of SRs focussed on the effectiveness of physical therapy, 20% virtual reality, 6% electromechanical devices, 4% Tai-Chi, whole body vibration and circuit training intervention, and 2% cognitive rehabilitation. The methodology of 54% of SRs were judged to be of a \u201clow or critically low\u201d quality, 23% \u201cmoderate\u201d quality and 22% \u201chigh\u201d quality. Conclusions There are 51 SRs of evidence relating to the effectiveness of interventions to improve balance in people with stroke, but the majority of these are of poor methodological quality, limiting our ability to draw clear implications. Only 22% of these SRs were judged to be of high quality, highlighting the need to address important methodological issues within rehabilitation research

Addressing the needs of traumatic brain injury with clinical proteomics.

BackgroundNeurotrauma or injuries to the central nervous system (CNS) are a serious public health problem worldwide. Approximately 75% of all traumatic brain injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of concussion injury today is limited to an assessment of behavioral symptoms, often with delay and subject to motivation. Hence, there is an urgent need for an accurate chemical measure in biofluids to serve as a diagnostic tool for invisible brain wounds, to monitor severe patient trajectories, and to predict survival chances. Although a number of neurotrauma marker candidates have been reported, the broad spectrum of TBI limits the significance of small cohort studies. Specificity and sensitivity issues compound the development of a conclusive diagnostic assay, especially for concussion patients. Thus, the neurotrauma field currently has no diagnostic biofluid test in clinical use.ContentWe discuss the challenges of discovering new and validating identified neurotrauma marker candidates using proteomics-based strategies, including targeting, selection strategies and the application of mass spectrometry (MS) technologies and their potential impact to the neurotrauma field.SummaryMany studies use TBI marker candidates based on literature reports, yet progress in genomics and proteomics have started to provide neurotrauma protein profiles. Choosing meaningful marker candidates from such 'long lists' is still pending, as only few can be taken through the process of preclinical verification and large scale translational validation. Quantitative mass spectrometry targeting specific molecules rather than random sampling of the whole proteome, e.g., multiple reaction monitoring (MRM), offers an efficient and effective means to multiplex the measurement of several candidates in patient samples, thereby omitting the need for antibodies prior to clinical assay design. Sample preparation challenges specific to TBI are addressed. A tailored selection strategy combined with a multiplex screening approach is helping to arrive at diagnostically suitable candidates for clinical assay development. A surrogate marker test will be instrumental for critical decisions of TBI patient care and protection of concussion victims from repeated exposures that could result in lasting neurological deficits

Interventions for improving upper limb function after stroke

Background: Improving upper limb function is a core element of stroke rehabilitation needed to maximise patient outcomes and reduce disability. Evidence about effects of individual treatment techniques and modalities is synthesised within many reviews. For selection of effective rehabilitation treatment, the relative effectiveness of interventions must be known. However, a comprehensive overview of systematic reviews in this area is currently lacking. Objectives: To carry out a Cochrane overview by synthesising systematic reviews of interventions provided to improve upper limb function after stroke. Methods: Search methods: We comprehensively searched the Cochrane Database of Systematic Reviews; the Database of Reviews of Effects; and PROSPERO (an international prospective register of systematic reviews) (June 2013). We also contacted review authors in an effort to identify further relevant reviews. Selection criteria: We included Cochrane and non‐Cochrane reviews of randomised controlled trials (RCTs) of patients with stroke comparing upper limb interventions with no treatment, usual care or alternative treatments. Our primary outcome of interest was upper limb function; secondary outcomes included motor impairment and performance of activities of daily living. When we identified overlapping reviews, we systematically identified the most up‐to‐date and comprehensive review and excluded reviews that overlapped with this. Data collection and analysis: Two overview authors independently applied the selection criteria, excluding reviews that were superseded by more up‐to‐date reviews including the same (or similar) studies. Two overview authors independently assessed the methodological quality of reviews (using a modified version of the AMSTAR tool) and extracted data. Quality of evidence within each comparison in each review was determined using objective criteria (based on numbers of participants, risk of bias, heterogeneity and review quality) to apply GRADE (Grades of Recommendation, Assessment, Development and Evaluation) levels of evidence. We resolved disagreements through discussion. We systematically tabulated the effects of interventions and used quality of evidence to determine implications for clinical practice and to make recommendations for future research. Main results: Our searches identified 1840 records, from which we included 40 completed reviews (19 Cochrane; 21 non‐Cochrane), covering 18 individual interventions and dose and setting of interventions. The 40 reviews contain 503 studies (18,078 participants). We extracted pooled data from 31 reviews related to 127 comparisons. We judged the quality of evidence to be high for 1/127 comparisons (transcranial direct current stimulation (tDCS) demonstrating no benefit for outcomes of activities of daily living (ADLs)); moderate for 49/127 comparisons (covering seven individual interventions) and low or very low for 77/127 comparisons. Moderate‐quality evidence showed a beneficial effect of constraint‐induced movement therapy (CIMT), mental practice, mirror therapy, interventions for sensory impairment, virtual reality and a relatively high dose of repetitive task practice, suggesting that these may be effective interventions; moderate‐quality evidence also indicated that unilateral arm training may be more effective than bilateral arm training. Information was insufficient to reveal the relative effectiveness of different interventions. Moderate‐quality evidence from subgroup analyses comparing greater and lesser doses of mental practice, repetitive task training and virtual reality demonstrates a beneficial effect for the group given the greater dose, although not for the group given the smaller dose; however tests for subgroup differences do not suggest a statistically significant difference between these groups. Future research related to dose is essential. Specific recommendations for future research are derived from current evidence. These recommendations include but are not limited to adequately powered, high‐quality RCTs to confirm the benefit of CIMT, mental practice, mirror therapy, virtual reality and a relatively high dose of repetitive task practice; high‐quality RCTs to explore the effects of repetitive transcranial magnetic stimulation (rTMS), tDCS, hands‐on therapy, music therapy, pharmacological interventions and interventions for sensory impairment; and up‐to‐date reviews related to biofeedback, Bobath therapy, electrical stimulation, reach‐to‐grasp exercise, repetitive task training, strength training and stretching and positioning. Authors' conclusions: Large numbers of overlapping reviews related to interventions to improve upper limb function following stroke have been identified, and this overview serves to signpost clinicians and policy makers toward relevant systematic reviews to support clinical decisions, providing one accessible, comprehensive document, which should support clinicians and policy makers in clinical decision making for stroke rehabilitation. Currently, no high‐quality evidence can be found for any interventions that are currently used as part of routine practice, and evidence is insufficient to enable comparison of the relative effectiveness of interventions. Effective collaboration is urgently needed to support large, robust RCTs of interventions currently used routinely within clinical practice. Evidence related to dose of interventions is particularly needed, as this information has widespread clinical and research implications

Spontaneous thought and vulnerability to mood disorders : the dark side of the wandering mind

There is increasing interest in spontaneous thought, namely task-unrelated or rest-related mental activity. Spontaneous thought is an umbrella term for processes like mind-wandering, involuntary autobiographical memory, and daydreaming, with evidence elucidating adaptive and maladaptive consequences. In this theoretical framework, we propose that, apart from its positive functions, spontaneous thought is a precursor for cognitive vulnerability in individuals who are at risk for mood disorders. It is important that spontaneous thought mostly focuses on unattained goals and evaluates the discrepancy between current and desired status. In individuals who stably (i.e., trait negative affectivity) or transitorily (i.e., stress) experience negative emotions in reaction to goal-discrepancy, spontaneous thought fosters major cognitive vulnerabilities (e.g., rumination, hopelessness, low self-esteem, and cognitive reactivity), which, in turn, enhance depression. Furthermore, we also highlight preliminary links between spontaneous thought and bipolar disorder. The evidence for this framework is reviewed, and we discuss theoretical and clinical implications of our proposal

Economic analysis of climate change adaptation strategies in selected coastal areas in Indonesia, Philippines and Vietnam

This report is an account of a cross-country study that covered Vietnam, Indonesia and the Philippines. Covering four sites (one each in Indonesia and Vietnam) and two sites in the Philippines, the study documented the impacts of three climate hazards affecting coastal communities, namely typhoon/flooding, coastal erosion and saltwater intrusion. It also analyzed planned adaptation options, which communities and local governments can implement, as well as autonomous responses of households to protect and insure themselves from these hazards. It employed a variety of techniques, ranging from participatory based approaches such as community hazard mapping and Focus Group Discussions (FGDs) to regression techniques, to analyze the impact of climate change and the behavior of affected communities and households