Computational Analysis of Geometric Effects on Strut Induced Mixing in a Scramjet Combustor

In order to increase the fuel-air mixing in a scramjet combustion section, the Air Force Institute of Technology and the Air Force Research lab investigated methods to increase the mixing efficiency. Previous experimental work identified the advantages of using a strut upstream of a cavity flame holder to increase the fuel-air mixture. In this paper a computational investigation of strut injectors in a supersonic flow with a cavity flame holder is reported. This research focused on understanding the effect of a change in height and width of the strut upstream of the combustion cavity on the mixing efficiency and pressure loss in the combustion section. Three baseline struts from the previous experimental research had slightly different trailing edge designs; a flat trailing edge, a 45 degree slanted trailing edge and a 6.45 cm extension. Twelve more struts were made from the baselines struts by varying the height and width by 50% of the baseline value. Computational simulations were conducted on all fifteen struts using the VULCAN computational fluid dynamics solver. Struts with a height or width increased from the baseline value exhibited an increase in the total pressure loss through the combustion section. This total pressure loss correlated to the larger low pressure region created by the flow displacement caused by the strut. The struts evaluated with decreased height and width showed a lower total pressure loss since they produced a smaller low pressure region in the wake. The low pressure region is key to the mixing caused by the struts. The larger struts caused a larger combustible area in the combustion section while the small struts produced a smaller combustible area. The size of the strut becomes a key design tradeoff between increased mixing and total loss performance

Recent data from radiofrequency denervation trials further emphasise that treating nociception is not the same as treating pain

Chronic low back pain is a condition that current health care provision is failing and we suggest that recent evidence from the interventional pain medicine field points to what these failings are. Radiofrequency denervation is performed on the presumption that denervation of a peripheral structure will eradicate or significantly reduce pain and improve function. The results of six moderately sized and well conducted clinical trials that demonstrate no efficacy and no real-world effectiveness for denervation procedures are a stark illustration of how flawed this approach is. We suggest that these results represent a line-in-the-sand for back pain research and management. This is a clear signal to finally abandon research agendas and management paradigms that focus primarily on nociception and instead, truly embrace the biopsychosocial model of pain

Reviews may overestimate the effectiveness of medicines for back pain: Systematic review and meta-analysis

Objective: Systematic-reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n=5 individual source systematic-reviews. We reproduced the meta-analyses using data available from the original reviews then re-ran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared to sham, for recent-onset low back pain from -21.71 (95%CI -28.23 to -15.19) to -2.34 (95%CI -3.34 to -1.34) on a 0-100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared to sham, for chronic low back pain from -10.10 (95%CI -12.81 to -7.39) to -9.31 (95%CI -11.51 to -7.11). The effect reduced in the subgroup of enriched design studies, from -12.40 (95%CI -16.90 to -7.91) to 11.34 (95%CI -15.36 to -7.32), and in the subgroup of non-enriched design studies; from -7.27 (95%CI -9.97 to -4.57) to -7.19 (95%CI -9.24 to -5.14). Conclusion: Systematic-reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful

Systematic reviews that include only published data may overestimate the effectiveness of analgesic medicines for low back pain: A systematic review and meta-analysis

Objective: Systematic reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n = 5 individual source systematic reviews. We reproduced the meta-analyses using data available from the original reviews and then reran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared with sham, for recent-onset low back pain from −21.71 (95% CI: −28.23 to −15.19) to −2.34 (95% CI: −3.34 to −1.34) on a 0–100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared with sham, for chronic low back pain from −10.10 (95% CI: −12.81 to −7.39) to −9.31 (95% CI: −11.51 to −7.11). The effect reduced in the subgroup of enriched design studies, from −12.40 (95% CI: −16.90 to −7.91) to −11.34 (95% CI: −15.36 to −7.32), and in the subgroup of nonenriched design studies, from −7.27 (95% CI: −9.97 to −4.57) to −7.19 (95% CI: −9.24 to −5.14). Conclusion: Systematic reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful

Changing the narrative in diagnosis and management of pain in the sacroiliac joint area

The sacroiliac joint (SIJ) is often considered to be involved when people present for care with low back pain where the sacroiliac joint (SIJ) is located. However, determining why the pain has arisen can be challenging, especially in the absence of a specific cause such as pregnancy, disease, or trauma, where the SIJ may be identified as a source of symptoms with the help of manual clinical tests. Nonspecific SIJ-related pain is commonly suggested to be causally associated with movement problems in the sacroiliac joint(s); a diagnosis traditionally derived from manual assessment of movements of the SIJ complex. Management choices often consist of patient education, manual treatment, and exercise. Although some elements of management are consistent with guidelines, this perspective argues that the assumptions on which these diagnoses and treatments are based are problematic, particularly if they reinforce unhelpful, pathoanatomical beliefs. This article reviews the evidence regarding the clinical detection and diagnosis of SIJ movement dysfunction. In particular, it questions the continued use of assessing movement dysfunction despite mounting evidence undermining the biological plausibility and subsequent treatment paradigms based on such diagnoses. Clinicians are encouraged to align their assessment methods and explanatory models to contemporary science to reduce the risk of their diagnoses and choice of intervention negatively affecting clinical outcome

Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain : systematic review and meta-analysis

Abstract: Objective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection: Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis: Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results: 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions: Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/

Paracetamol, NSAIDS and opioid analgesics for chronic low back pain: A network meta-analysis (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To answer the clinical question: ‘what analgesic medicine shall I prescribe this patient with chronic low back pain to reduce their pain?’. The objectives are to determine the analgesic effects, safety, effect on function, and relative rank according to analgesic effect, safety and effect on function of a single course of opioid analgesics, NSAIDs or paracetamol or combinations of these medicines

The RESOLVE Trial for people with chronic low back pain: Statistical analysis plan

Background: Statistical analysis plans describe the planned data management and analysis for clinical trials. This supports transparent reporting and interpretation of clinical trial results. This paper reports the statistical analysis plan for the RESOLVE clinical trial. The RESOLVE trial assigned participants with chronic low back pain to graded sensory-motor precision training or sham-control. Results: We report the planned data management and analysis for the primary and secondary outcomes. The primary outcome is pain intensity at 18-weeks post randomization. We will use mixed-effects models to analyze the primary and secondary outcomes by intention-to-treat. We will report adverse effects in full. We also describe analyses if there is non-adherence to the interventions, data management procedures, and our planned reporting of results. Conclusion: This statistical analysis plan will minimize the potential for bias in the analysis and reporting of results from the RESOLVE trial. Trial registration: ACTRN12615000610538 (https://www.anzctr.org.au/Trial/Registration/ TrialReview.aspx?id=368619). © 2020 Associac¸ao˜ Brasileira de Pesquisa e Pos-Graduac ´ ¸ao˜ em Fisioterapia. Published by Elsevier Editora Ltda. All rights reserved

Genomic profiling for clinical decision making in myeloid neoplasms and acute leukemia

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome sequencing, whole-genome sequencing, and whole-transcriptome sequencing or RNA sequencing. In patients with myeloid neoplasms, whole-genome sequencing represents a potential replacement for both conventional cytogenetic and sequencing approaches, providing rapid and accurate comprehensive genomic profiling. DNA sequencing methods are used not only for detecting somatically acquired gene mutations but also for identifying germline gene mutations associated with inherited predisposition to hematologic neoplasms. The 2022 International Consensus Classification of myeloid neoplasms and acute leukemias makes extensive use of genomic data. The aim of this report is to help physicians and laboratorians implement genomic testing for diagnosis, risk stratification, and clinical decision making and illustrates the potential of genomic profiling for enabling personalized medicine in patients with hematologic neoplasms