REPORT-SCS: minimum reporting standards for spinal cord stimulation studies in spinal cord injury

Objective. Electrical spinal cord stimulation (SCS) has emerged as a promising therapy for recovery of motor and autonomic dysfunctions following spinal cord injury (SCI). Despite the rise in studies using SCS for SCI complications, there are no standard guidelines for reporting SCS parameters in research publications, making it challenging to compare, interpret or reproduce reported effects across experimental studies. Approach. To develop guidelines for minimum reporting standards for SCS parameters in pre-clinical and clinical SCI research, we gathered an international panel of expert clinicians and scientists. Using a Delphi approach, we developed guideline items and surveyed the panel on their level of agreement for each item. Main results. There was strong agreement on 26 of the 29 items identified for establishing minimum reporting standards for SCS studies. The guidelines encompass three major SCS categories: hardware, configuration and current parameters, and the intervention. Significance. Standardized reporting of stimulation parameters will ensure that SCS studies can be easily analyzed, replicated, and interpreted by the scientific community, thereby expanding the SCS knowledge base and fostering transparency in reporting

Moving stroke rehabilitation evidence into practice: a systematic review of randomized controlled trials

Objective To investigate the effectiveness of interventions aimed at moving research evidence into stroke rehabilitation practice through changing the practice of clinicians. Data sources EMBASE, CINAHL, Cochrane and MEDLINE databases were searched from 1980 to April 2019. International trial registries and reference lists of included studies completed our search. Review methods Randomized controlled trials that involved interventions aiming to change the practice of clinicians working in stroke rehabilitation were included. Bias was evaluated using Revman to generate a risk of bias table. Evidence quality was evaluated using GRADE criteria. Results Sixteen trials were included (250 sites, 14,689 patients), evaluating a range of interventions including facilitation, audit and feedback, education, and reminders. Eleven studies included multicomponent interventions (using a combination of interventions). Four used educational interventions alone and one used electronic reminders. Risk of bias was generally low. Overall, the GRADE criteria indicated that this body of literature was low quality. This review found higher efficacy of trials which targeted fewer outcomes. Subgroup analysis indicated moderate level GRADE evidence (103 sites, 10,877 patients) that trials which included both site facilitation and tailoring for local factors were effective in changing clinical practice. The effect size of these varied (OR 1.63-4.9). Education interventions alone were not effective. Conclusions A large range of interventions are used to facilitate clinical practice change. Education is commonly used, but in isolation is not effective. Multicomponent interventions including facilitation and tailoring to local settings can change clinical practice and are more effective when targeting fewer changes

Examination of a pre-exercise, high energy supplement on exercise performance

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effect of a pre-exercise high energy drink on reaction time and anaerobic power in competitive strength/power athletes. In addition, the effect of the pre-exercise drink on subjective feelings of energy, fatigue, alertness and focus was also explored.</p> <p>Methods</p> <p>Twelve male strength/power athletes (21.1 ± 1.3 y; 179.8 ± 7.1 cm; 88.6 ± 12.1 kg; 17.6 ± 3.3% body fat) underwent two testing sessions administered in a randomized and double-blind fashion. During each session, subjects reported to the Human Performance Laboratory and were provided with either 120 ml of a high energy drink (SUP), commercially marketed as Redline Extreme^®or 120 ml of a placebo (PL) that was similar in taste and appearance but contained no active ingredients. Following consumption of the supplement or placebo subjects rested quietly for 10-minutes prior to completing a survey and commencing exercise. The survey consisted of 4 questions asking each subject to describe their feelings of energy, fatigue, alertness and focus for that moment. Following the completion of the questionnaire subjects performed a 2-minute quickness and reaction test on the Makoto testing device (Makoto USA, Centennial CO) and a 20-second Wingate Anaerobic Power test. Following a 10-minute rest subjects repeated the testing sequence and after a similar rest period a third and final testing sequence was performed. The Makoto testing device consisted of subjects reacting to both a visual and auditory stimulus and striking one out of 30 potential targets on three towers.</p> <p>Results</p> <p>Significant difference in reaction performance was seen between SUP and PL in both average number of targets struck (55.8 ± 7.4 versus 51.9 ± 7.4, respectively) and percent of targets struck (71.9 ± 10.5% versus 66.8 ± 10.9%, respectively). No significant differences between trials were seen in any anaerobic power measure. Subjective feelings of energy (3.5 ± 0.5 versus 3.1 ± 0.5) and focus (3.8 ± 0.5 versus 3.3 ± 0.7) were significantly higher during SUP compared to PL, respectively. In addition, a trend towards an increase in average alertness (p = 0.06) was seen in SUP compared to P.</p> <p>Conclusion</p> <p>Results indicate a significant increase in reaction performance, with no effect on anaerobic power performance. In addition, ingestion of this supplement significantly improves subjective feelings of focus and energy in male strength/power athletes.</p

Breath biomarkers in idiopathic pulmonary fibrosis:A systematic review 11 Medical and Health Sciences

Background: Exhaled biomarkers may be related to disease processes in idiopathic pulmonary fibrosis (IPF) however their clinical role remains unclear. We performed a systematic review to investigate whether breath biomarkers discriminate between patients with IPF and healthy controls. We also assessed correlation with lung function, ability to distinguish diagnostic subgroups and change in response to treatment. Methods: MEDLINE, EMBASE and Web of Science databases were searched. Study selection was limited to adults with a diagnosis of IPF as per international guidelines. Results: Of 1014 studies screened, fourteen fulfilled selection criteria and included 257 IPF patients. Twenty individual biomarkers discriminated between IPF and controls and four showed correlation with lung function. Meta-analysis of three studies indicated mean (± SD) alveolar nitric oxide (CalvNO) levels were significantly higher in IPF (8.5 ± 5.5 ppb) than controls (4.4 ± 2.2 ppb). Markers of oxidative stress in exhaled breath condensate, such as hydrogen peroxide and 8-isoprostane, were also discriminatory. Two breathomic studies have isolated discriminative compounds using mass spectrometry. There was a lack of studies assessing relevant treatment and none assessed differences in diagnostic subgroups. Conclusions: Evidence suggests CalvNO is higher in IPF, although studies were limited by small sample size. Further breathomic work may identify biomarkers with diagnostic and prognostic potential

NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

Background: Recent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders. Objective: To study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population. Methods: NLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin. Results: Conditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA. Conclusions: Our results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease

Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB as Novel Risk Loci for Systemic Sclerosis

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10−5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10−8, OR = 0.69, 95% CI [0.60–0.79]; rs6457617, P = 1.14×10−7 and rs9275245, P = 1.39×10−7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10−5, OR = 1.36 [1.18–1.56]) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10−5) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10−10, OR:1.25), TNIP1 (P = 4.68×10−9, OR:1.31), and RHOB loci (P = 3.17×10−6, OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies