Brazilian Jiu-Jitsu–Related Post-Concussion Symptoms Ameliorated With Neurorehabilitation

ObjectiveDiscuss neurorehabilitation efficacy in a case of concussion without direct head impact.BackgroundWhile there is growing concern about the prevalence and severity of concussion in mixed martial arts, a grappling component, Brazilian Jiu-Jitsu, is not typically perceived as high risk. Rapid acceleration or deceleration without direct head trauma led to a concussion for a 15-year-old male during jiu-jitsu throwing drills. The subject and parents reported difficulty with academic performance, social interactions, and emotional regulation. Symptoms persisted for 4 months before care was sought by the subject and his parents. Without direct head trauma or impact, concussion was not initially suspected.Design/MethodsThirteen sessions of treatment were performed in a neurorehabilitation setting utilizing joint manipulation, vestibular rehabilitation with a whole-body off-axis rotation device, oculomotor exercises, neuromuscular re-education, and electrical stimulation. C3 Logix was utilized as a baseline (immediately preceding second treatment due to equipment difficulties) and at discharge to measure effects of treatment.ResultsData is reported as “(baseline, discharge, percent-change).” Graded Symptom Checklist score out of 162 (91, 20; −78.02%), Trail Making Test A (sec) (26.8, 19.7; −26.49%), Trail Making Test B (sec) (69.9, 37.9; −45.78%), Digit-Symbol Matching speed (# of symbols) (66, 71; +7.58%), Choice reaction time (msec) (452, 397; −12.17), Static:Dynamic Visual Acuity (line difference) (1, 0.4; −60%). Subjectively, the subject and his parents reported improved academic performance, social interactions, and emotional regulation leading to a better home and educational experience for all involved.ConclusionsThis case displays positive clinical improvements with a functional neurology approach to outpatient neurorehabilitation. Further investigation into this multimodal rehabilitation for post-concussion symptoms, with and without direct head impact, is recommended. Continued concussion education and awareness are recommended for sports with rapid acceleration or deceleration and limited direct head impact.

PP216 Indirect Treatment Comparison Assessment: An Improvement Intervention In The Scottish Medicines Consortium

IntroductionThe Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of the National Health Service Scotland based on pharmaceutical company submissions. As the appraisals are conducted close to the point of marketing authorization, there is often a lack of direct head-to-head data. In 2019, assessment of relevant comparative efficacy was informed via indirect treatment comparisons (ITC) in 55 percent (36/66) of submissions. While the ITCs are essential to the decision-making process, they are frequently incomplete.MethodsA focus group was conducted with the clinical assessment team (n = 11) to explore problems in the submission process and to identify areas for improvement. It was agreed that providing improved guidance to companies prior to submission may prevent future inconsistencies. A working group (n = 5) was tasked with identifying and implementing potential solutions. The group reviewed the focus group findings, relevant literature, and guidance from other organizations. Draft guidance was developed that was reviewed by two pharmaceutical industry representatives (SMC subcommittee members).ResultsFindings from the focus group highlighted issues broadly related to the incomplete presentation and reporting of ITCs. The improved guidance document outlined specific requirements in a checklist format for reporting and presenting the results of different ITC data. This guidance was published in February 2020. To evaluate the impact of the updated guidance and to identify any further changes required, a follow-up focus group and survey of industry representatives is planned for March 2021.ConclusionsThe aim of the ITC guidance is to provide pharmaceutical companies with direction to improve the quality and transparency of reporting, which will in turn improve the quality of HTAs and thus strengthen the recommendations provided by the SMC. The follow-up focus groups and survey will assess the impact of the guidance. It is acknowledged that the results of this process may be limited by the small sample size and short duration of the assessment.

Psoriasis to Psoriatic Arthritis: The Application of Proteomics Technologies

Psoriatic disease (PsD) is a spectrum of diseases that affect both skin [cutaneous psoriasis (PsC)] and musculoskeletal features [psoriatic arthritis (PsA)]. A considerable number of patients with PsC have asymptomatic synovio-entheseal inflammations, and approximately one-third of those eventually progress to PsA with an enigmatic mechanism. Published studies have shown that early interventions to the very early-stage PsA would effectively prevent substantial bone destructions or deformities, suggesting an unmet goal for exploring early PsA biomarkers. The emergence of proteomics technologies brings a complete view of all involved proteins in PsA transitions, offers a unique chance to map all potential peptides, and allows a direct head-to-head comparison of interaction pathways in PsC and PsA. This review summarized the latest development of proteomics technologies, highlighted its application in PsA biomarker discovery, and discussed the possible clinical detectable PsA risk factors in patients with PsC.

Comparison of Treatment Modalities in Frontline Therapy of Stages I/IE Extranodal NK/T-Cell Lymphoma-Nasal Type (ENKTL-N): An up-to-Date Network Meta-Analysis

Introduction: Despite many studies reporting on the optimal therapies for early stage ENKTL-N in the front-line setting, this area continues to be subject to a significant controversy regarding single modalities versus combination or sequential approaches. All these comparative studies were small non-randomized studies that combined stages I & II. The results were often inconclusive and occasionally conflicting. In the absence of direct head-to-head randomized controlled trials in this clinical setting, a network meta-analysis was conducted to compare these therapeutic approaches and their respective impact on 5-year survival in stage I/IE ENKTL-N. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of stage I/IE ENKTL-N, treatment with chemotherapy (CT), radiation (RT), sequential CT and RT (SEQ), and chemoradiotherapy (CRT), comparative studies that reported predominantly (>70%) I/IE 5-year overall survival (OS) and disease-free survival (DFS) rates. Studies that reported on mixed samples of early and advanced ENKTL were excluded. A frequentist network meta-analysis was conducted using the netmeta package and random-effects model. Results: Seven studies comprising a total of 397 participants were included. Our network meta-analysis revealed that upfront RT tended to have better 5-year OS and DFS than CRT, SEQ, though it did not reach statistical significance. However, RT had a significantly superior 5-year OS when compared to CT (RR=0.43, 0.19-0.97). Based on the pair-wise and network meta-analyses, RT was ranked as the most effective first-line treatment approach followed by CRT, SEQ, and CT in decreasing order. Analysis of the 5-year DFS yielded similar findings. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates. Conclusion: This is the first network meta-analysis to compare all commonly utilized upfront treatment modalities in stages I/IE ENKTL-N. It indicates that upfront RT alone may be sufficient as there was no signal that chemotherapy added any OS or DFS advantages. Adequately powered randomized trials are warranted. Disclosures No relevant conflicts of interest to declare.

Methods for the inclusion of real-world evidence in network meta-analysis

Background Network Meta-Analysis (NMA) is a key component of submissions to reimbursement agencies world-wide, especially when there is limited direct head-to-head evidence for multiple technologies from randomised controlled trials (RCTs). Many NMAs include only data from RCTs. However, real-world evidence (RWE) is also becoming widely recognised as a valuable source of clinical data. This study aims to investigate methods for the inclusion of RWE in NMA and its impact on the level of uncertainty around the effectiveness estimates, with particular interest in effectiveness of fingolimod. Methods A range of methods for inclusion of RWE in evidence synthesis were investigated by applying them to an illustrative example in relapsing remitting multiple sclerosis (RRMS). A literature search to identify RCTs and RWE evaluating treatments in RRMS was conducted. To assess the impact of inclusion of RWE on the effectiveness estimates, Bayesian hierarchical and adapted power prior models were applied. The effect of the inclusion of RWE was investigated by varying the degree of down weighting of this part of evidence by the use of a power prior. Results Whilst the inclusion of the RWE led to an increase in the level of uncertainty surrounding effect estimates in this example, this depended on the method of inclusion adopted for the RWE. ‘Power prior’ NMA model resulted in stable effect estimates for fingolimod yet increasing the width of the credible intervals with increasing weight given to RWE data. The hierarchical NMA models were effective in allowing for heterogeneity between study designs, however, this also increased the level of uncertainty. Conclusion The ‘power prior’ method for the inclusion of RWE in NMAs indicates that the degree to which RWE is taken into account can have a significant impact on the overall level of uncertainty. The hierarchical modelling approach further allowed for accommodating differences between study types. Consequently, further work investigating both empirical evidence for biases associated with individual RWE studies and methods of elicitation from experts on the extent of such biases is warranted.

Evidence in crisis: a closer look into the quality of published systematic reviews in the cardiology literature

Background Systematic reviews are usually considered as the highest level of evidence and are increasingly used in shaping cardiology policies and guidelines. However, as the rate of publishing systematic reviews increases annually, there are rising concerns regarding their quality and reporting standards. Purpose The current analysis provides an insight into the quality of published systematic reviews in cardiology and provides recommendations for researchers, clinicians, and stakeholders in this regard. Methods Using a comprehensive Medline/PubMed search, we retrieved all systematic reviews, published between 2009 and 2019 in five general cardiology journals with the highest impact factor as per the Clarivate Analytics 2019 Journal Impact Factor List (Circulation, European Heart Journal, Journal of the American College of Cardiology, Circulation Research, and JAMA Cardiology). We assessed the methodological characteristics, eligibility criteria, reporting standards, as well as review quality scores according to the AMSTAR tool. Results Among 352 retrieved reviews, 275 (75.3%) performed direct head-to-head analysis and 164 (46.6%) included only clinical trials. The median numbers of searched databases and included studies were 3 (IQR: 2, 3) and 13 (IQR: 7, 30). The primary outcomes were often hard clinical endpoints as mortality (39.2%) and stroke (11.9%). 64 (18.2%) registered their protocol, 208 (58.4%) used validated tools for risk of bias assessment, 177 (52.3%) assessed for publication bias, and 221 (62.8%) adhered to the PRISMA checklist. Thirty-five reviews detected significant publication bias, which was significantly associated with heterogeneity of the primary outcome. The AMSTAR quality scores were low or critically low in 71% of evaluated reviews. Further, 87 (24.7%) did not report on whether they received funding or not, 33 (9.4%) reported receiving no funding, and 232 adequately reported on their funding sources [70 (19.9%) from governmental/academic sources, 120 (34.1%) from pharmaceutical companies, and 42 (11.9%) from both sources]. analysis showed that reviews with advanced statistical analysis, those that included RCTs, adhered to the PRISMA checklist, or had higher AMSTAR quality scores had significantly higher citation metrics (p<0.05). Conclusion Due to the widespread low quality and poor reporting in cardiovascular systematic reviews, clinicians should be educated on the value of methodological quality in interpreting systematic review findings. In addition, academic societies and guideline writing groups should implement rigorous critical appraisal and peer review policies to improve the synthesis and utilization of systematic reviews in evidence-based cardiovascular medicine. FUNDunding Acknowledgement Type of funding sources: None.

Reversible P2Y12 inhibitor versus irreversible P2Y12 inhibitor in ACS patients undergoing PCI (the acute coronary syndrome israeli survey (ACSIS)

Introduction Based on data from randomized controlled trials, both American and European guidelines recommend treating acute coronary syndrome (ACS) patients with second generation P2Y12 inhibitors.1,2 Direct head-to-head comparison of these agents was scarce until the recent publication of the ISAR-REACT-5 study which demonstrated the superiority of the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) over the reversible P2Y12 inhibitor in terms of 1-year composite of death, myocardial infarction (MI), and stroke.3,4,5 Given the unexpected outcomes of this trial, we sought to perform a comparison of ticagrelor and prasugrel in real-life ACS patients. Purpose To compare the outcomes of ACS (acute coronary syndrome) patients undergoing in-hospital PCI (percutaneous coronary intervention) treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) versus the reversible P2Y12 inhibitor. Methods ACSIS (Acute Coronary Syndrome in Israel) is a national ACS snapshot survey conducted in all 25 cardiology departments in Israel since 2000 over a two-month period, every two to three years. Both the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and the reversible P2Y12 inhibitor were commercially introduced in Israel in 2010. We therefore considered patients enrolled in ACSIS surveys 2010–2018 for the present analysis. Results Among 7,233 patients enrolled to the ACSIS (Acute Coronary Syndrome in Israel) registry between 2010 and 2018, we identified 1133 eligible patients treated with the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) and 825 with the reversible P2Y12 inhibitor. In hospital complication rates, including rates of stent thrombosis, were roughly similar between groups. Compared to the reversible P2Y12 inhibitor, the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was associated with lower 1-year death in ST-elevation myocardial infarction (STEMI) patient compared to non-ST-elevation ACS (NSTE-ACS) patients (p for interaction 0.03). In propensity score matched STEMI patients (502 receiving the Irreversible thienopyridine type P2Y12 inhibitor (prodrug), 251 the reversible P2Y12 inhibitor) 30-day re-hospitalization rate (p<0.05), 30-day MACE (the composite of death, MI, stroke, urgent revascularization; p=0.006), and 1-year mortality rates (p=0.08) were higher in the the reversible P2Y12 inhibitor group compared to the the Irreversible thienopyridine type P2Y12 inhibitor (prodrug) group; In NSTE-ACS patients, outcomes were not impacted by drug choice. Conclusion The Irreversible thienopyridine type P2Y12 inhibitor (prodrug) was more effective than the reversible P2Y12 inhibitor in STEMI patients, but not in NSTE-ACS patients. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Israeli working group on acute cardiac care of the Israel heart society

Cancer-related fatigue—pharmacological interventions: systematic review and network meta-analysis

IntroductionCancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.MethodsMedline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.ResultsThis review reports on 20 studies and 2688 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to both methylphenidate and modafinil.ConclusionParoxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.

Video Analysis and Verification of Direct Head Impacts Recorded by Wearable Sensors in Junior Rugby League Players

Background Rugby league is a high-intensity collision sport that carries a risk of concussion. Youth athletes are considered to be more vulnerable and take longer to recover from concussion than adult athletes. Purpose To review head impact events in elite-level junior representative rugby league and to verify and describe characteristics of X-patchTM-recorded impacts via video analysis. Study Design Observational case series. Methods The X-patchTM was used on twenty-one adolescent players (thirteen forwards and eight backs) during a 2017 junior representative rugby league competition. Game-day footage, recorded by a trained videographer from a single camera, was synchronised with X-patchTM-recorded timestamped events. Impacts were double verified by video review. Impact rates, playing characteristics, and gameplay situations were described. Results The X-patchTM-recorded 624 impacts ≥ 20g between game start and finish, of which 564 (90.4%) were verified on video. Upon video review, 413 (73.2%) of all verified impacts ≥ 20g where determined to be direct head impacts. Direct head impacts ≥ 20g occurred at a rate of 5.2 impacts per game hour; 7.6 for forwards and 3.0 for backs (range = 0–18.2). A defender’s arm directly impacting the head of the ball carrier was the most common event, accounting for 21.3% (n = 120) of all impacts, and 46.7% of all “hit-up” impacts. There were no medically diagnosed concussions during the competition. Conclusion The majority (90.4%) of head impacts ≥ 20g recorded by the X-patchTM sensor were verified by video. Double verification of direct head impacts in addition to cross-verification of sensor-recorded impacts using a secondary source such as synchronised video review can be used to ensure accuracy and validation of data.