Application of Asthma Prediction Tools in a Cohort of Infants with Severe Bronchiolitis.

Background: Severe bronchiolitis is a strong childhood asthma risk factor. Early and accurate asthma prediction is key. We applied the Asthma Predictive Index (API), the modified Asthma Predictive Index (mAPI), and the Pediatric Asthma Risk Score (PARS) in a cohort of high-risk infants to predict asthma at age 6 years. Methods: We conducted a 17-center cohort of infants (age <1 year) hospitalized with severe bronchiolitis during 2011-2014. We used only infancy data to predict asthma at age 6 years. Results: The prevalence of parent-reported asthma at age 6 years was 328/880 (37%). The prevalences of a positive index/score for stringent and loose API, mAPI, and PARS were 21%, 51%, 11%, and 34%, respectively. Area under the receiver operating characteristic curves [95% confidence interval (CI)] ranged from 0.57 (95% CI 0.55-0.60) for mAPI to 0.66 (95% CI 0.63-0.70) for PARS. Conclusions: An asthma prediction tool for high-risk infants is needed to identify those who would benefit most from asthma prevention interventions.

Performance of Three Asthma Predictive Tools in a Cohort of Infants Hospitalized With Severe Bronchiolitis.

Childhood asthma develops in 30-40% of children with severe bronchiolitis but accurate prediction remains challenging. In a severe bronchiolitis cohort, we applied the Asthma Predictive Index (API), the modified Asthma Predictive Index (mAPI), and the Pediatric Asthma Risk Score (PARS) to predict asthma at age 5 years. We applied the API, mAPI, and PARS to the 17-center cohort of infants hospitalized with severe bronchiolitis during 2011-2014 (35th Multicenter Airway Research Collaboration, MARC-35). We used data from the first 3 years of life including parent interviews, chart review, and specific IgE testing to predict asthma at age 5 years, defined as parent report of clinician-diagnosed asthma. Among 875/921 (95%) children with outcome data, parent-reported asthma was 294/875 (34%). In MARC-35, a positive index/score for stringent and loose API, mAPI, and PARS were 24, 68, 6, and 55%, respectively. The prediction tools' AUCs (95%CI) ranged from 0.57 (95%CI 0.54-0.59) to 0.68 (95%CI 0.65-0.71). The positive likelihood ratios were lower in MARC-35 compared to the published results from the original cohorts. In this high-risk population of infants hospitalized with severe bronchiolitis, API, mAPI, and PARS had sub-optimal performance (AUC <0.8). Highly accurate (AUC >0.8) asthma prediction tools are desired in infants hospitalized with severe bronchiolitis.

Intracortical Inhibition in the Affected Hemisphere in Limb Amputation.

Phantom limb pain (PLP) affects up to 80% of amputees. Despite the lack of consensus about the etiology and pathophysiology of phantom experiences, previous evidence pointed out the role of changes in motor cortex excitability as an important factor associated with amputation and PLP. In this systematic review, we investigated changes in intracortical inhibition as indexed by transcranial magnetic stimulation (TMS) in amputees and its relationship to pain. Four electronic databases were screened to identify studies using TMS to measure cortical inhibition, such as short intracortical inhibition (SICI), long intracortical inhibition (LICI) and cortical silent period (CSP). Seven articles were included and evaluated cortical excitability comparing the affected hemisphere with the non-affected hemisphere or with healthy controls. None of them correlated cortical disinhibition and clinical parameters, such as the presence or intensity of PLP. However, most studies showed decreased SICI in amputees affected hemisphere. These results highlight that although SICI seems to be changed in the affected hemisphere in amputees, most of the studies did not investigate its clinical correlation. Thus, the question of whether they are a valid diagnostic marker remains unanswered. Also, the results were highly variable for both measurements due to the heterogeneity of study designs and group comparisons in each study. Although these results underscore the role of inhibitory networks after amputation, more studies are needed to investigate the role of a decreased inhibitory drive in the motor cortex to the cause and maintenance of PLP.

Noninvasive motor cortex stimulation effects on quantitative sensory testing in healthy and chronic pain subjects: a systematic review and meta-analysis.

ABSTRACT: One of the potential mechanisms of motor cortex stimulation by noninvasive brain stimulation (NIBS) effects on pain is through the restoration of the defective endogenous inhibitory pain pathways. However, there are still limited data on quantitative sensory testing (QST), including conditioned pain modulation (CPM), supporting this mechanism. This systematic review and meta-analysis aimed to evaluate the effects of noninvasive motor cortex stimulation on pain perception as indexed by changes in QST outcomes. Database searches were conducted until July 2019 to include randomized controlled trials that performed sham-controlled NIBS on the motor cortex in either the healthy and/or pain population and assessed the QST and CPM. Quality of studies was assessed through the Cochrane tool. We calculated the Hedge's effect sizes of QST and CPM outcomes and their 95% confidence intervals (95% CIs) and performed random-effects meta-analyses. Thirty-eight studies were included (1178 participants). We found significant increases of pain threshold in healthy subjects (ES = 0.16, 95% CI = 0.02-0.31, I2 = 22.2%) and pain populations (ES = 0.48, 95% CI = 0.15-0.80, I2 = 68.8%), and homogeneous higher CPM effect (pain ratings reduction) in healthy subjects (ES = -0.39, 95% CI = -0.64 to -0.14, I2 = 17%) and pain populations (ES = -0.35, 95% CI = -0.60 to -0.11, I2 = 0%) in the active NIBS group compared with sham. These results support the idea of top-down modulation of endogenous pain pathways by motor cortex stimulation as one of the main mechanisms of pain reduction assessed by QST, which could be a useful predictive and prognostic biomarker for chronic pain personalized treatment with NIBS.

The Impact of Rehabilitation-oriented Virtual Reality Device in Patients With Ischemic Stroke in the Early Subacute Recovery Phase: Study Protocol for a Phase III, Single-Blinded, Randomized, Controlled Clinical Trial.

BACKGROUND AND RATIONALE: Stroke is considered the most common cause of adult disability. Intensive rehabilitation protocols outperform nonintensive counterparts. The subacute stroke phase represents a potential window to recovery. Virtual reality (VR) has been shown to provide a more stimulating environment, allowing for increased patient compliance. However, the quality of current literature comparing VR with standard therapies is limited. Our aim is to measure the impact of VR versus standard therapy on the recovery of the upper limb motor function in patients with stroke in the early subacute recovery phase. METHOD: This is a randomized, controlled trial that will assign 262 patients to tailor-made standard rehabilitation (TMSR) or TMSR plus immersive VR device. The trial will be conducted in an urban rehabilitation clinic in the United States with expertise in the management of poststroke patients. Patients will be 18 to 70 years of age and in the early subacute period (30-90 days post ischemic stroke). The primary outcome will be the change of Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score, measured at baseline and 13 weeks after randomization. The secondary outcome will be the change in the UK Functional Independence Measure and Functional Assessment Measure (UK FIM-FAM) score at the same time points. DISCUSSION: If the use of VR in the rehabilitation of patients with stroke proves to have a significant impact on their motor recovery, it will constitute an extremely important step into decreasing the functional impairment associated with stroke and the related health care expense burden.

Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.

INTRODUCTION: Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control. METHODS AND ANALYSIS: A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)-primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study-CPM and TSPS-and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables. ETHICS AND DISSEMINATION: This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBER: NCT03371225.