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Chad Williamson,1 Barbara J Martin,2 Charles Argoff,3 Christopher Gharibo,4 Bill McCarberg,5 Timothy Atkinson,6 Leanne Berger,1 Thomas Sullivan1 1Rockpointe, Columbia, MD, USA; 2Independent Consultant Physician/Writer, Lancaster, PA, USA; 3Albany Medical College, Albany, NY, USA; 4New York University School of Medicine, New York City, NY, USA; 5University of California, San Diego, CA, USA; 6Veteran’s Administration Tennessee Valley Healthcare System, Nashville, TN, USACorrespondence: Chad WilliamsonRockpointe, 1760 Russet Hill Circle, Hoover, AL, 35244, USATel +1-205-266-5568Email cwilliamson@rockpointe.comIntroduction: Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A “blueprint” of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018.Methods: To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management.Results: Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain.Discussion: These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.Keywords: analgesics, opioid, chronic pain, pain management, opioid-related disorders, primary health care, continuing medical education, CME, risk evaluation and mitigation strategy, REMS

Abstract Background The rectus femoris muscle plays an important role in maintaining lower limb stability and biomechanical control during basic physical activities. Both reduced quadriceps strength and decreased muscle thickness of the rectus femoris, as measured by ultrasound, are associated with an increased risk of falls in older adults. We estimated the relative and absolute intra-rater, inter-rater, and inter-day reliability of the procedure. Methods A female biologist and a male physical educator, both holding a master’s degree in human movement and rehabilitation, captured ultrasound images of the right rectus femoris muscle in 106 healthy participants (58 females and 48 males), aged 18 to 73 years. Each rater captured three images per participant during each visit, with two visits 7 to 10 days apart. A third person subsequently measured the muscle thickness. We calculated the Intraclass Correlation Coefficients (ICC) using a two-way random model and determined the 95% minimal detectable difference (MDD). Results The mean muscle thickness was 2.12 cm. The reliability based on single measurements was as follows: the intra-rater ICC for raters A and B was 0.998 at both visits (MDDs: 0.074–0.082 cm). The inter-rater ICC was 0.976 at visit 1 and 0.977 at visit 2 (MDDs: 0.269–0.270 cm). The inter-day ICC was 0.973 for rater A and 0.972 for rater B (MDDs: 0.286–0.291 cm). Sensitivity analyses accounting for age, sex, and the use of mean measurements produced similar results. The results were homoscedastic. Conclusions The rectus femoris muscle thickness was measured with good reliability using ultrasonography across all the settings.

Abstract Background Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia. Methods This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student’s t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio

Background: Acute mesenteric venous thrombosis (MVT) is rarely suspected as primary diagnosis in emergency departments and still carries an in-hospital mortality rate of above 20%. Objectives: The aim of this study was to find differences in clinical and laboratory markers between patients with acute MVT and a control group of suspected but confirmed as not having any type of acute mesenteric ischaemia (AMI). Design: Data was retrieved from the AMESI (Acute MESenteric Ischaemia) study. This international, multicenter prospective case-control study from 32 sites collected data on patients with suspected AMI during a 10-month period. Methods: Independent factors associated with acute MVT were evaluated in a multivariable logistic regression analysis and expressed as odds ratios (OR) with 95% confidence intervals (CI). Results: D-dimer was not significantly higher in MVT (n = 73) compared to non-AMI (n = 287) patients (median 7.0 mg/L vs 4.5 mg/L, P = .092). After entering BMI, atherosclerotic disease, history of venous thromboembolism, CRP, and D-dimer as covariates in a multi-variable logistic regression analysis, absence of atherosclerotic disease (OR 0.096, 95% CI 0.011-0.84; P = .034) and elevated D-dimer (OR 2.59/one SD increment, 95% CI 1.07-6.28; P = .034) were associated with MVT. The discriminative ability of D-dimer for MVT as assessed by area under the curve in the receiver operating characteristics analysis was 0.63 (95% CI 0.49-0.78). Conclusion: Elevated D-dimer was associated with MVT, but the discriminative ability of D-dimer was poor. There is an urgent need to find a more accurate plasma biomarker for this condition. TRIAL REGISTRATION: NCT05218863 (registered 19.01.2022).

Abstract Background Acute mesenteric ischaemia (AMI) is a disease with different pathophysiological mechanisms, leading to a life-threatening condition that is difficult to diagnose based solely on clinical signs. Despite widely acknowledged need for biomarkers in diagnosis of AMI, a broad systematic review on all studied biomarkers in different types of AMI is currently lacking. The aim of this study was to estimate the diagnostic accuracy of all potential biomarkers of AMI studied in humans. Methods A systematic literature search in PubMed, The Cochrane Library, Web of Science and Scopus was conducted in December 2022. Studies assessing potential biomarkers of AMI in (at least 10) adult patients and reporting their diagnostic accuracy were included. Meta-analyses of biomarkers’ sensitivity, specificity, and positive and negative likelihood ratios were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed with the QUADAS-2 tool. Results Seventy-five studies including a total of 9914 patients assessed 18 different biomarkers in serum/plasma and one in urine (each reported in at least two studies), which were included in meta-analyses. None of the biomarkers reached a conclusive level for accurate prediction. The best predictive value overall (all studies with any type and stage of AMI pooled) was observed for Ischaemia-modified albumin (2 studies, sensitivity 94.7 and specificity 90.5), interleukin-6 (n = 4, 96.3 and 82.6), procalcitonin (n = 6, 80.1 and 86.7), and intestinal fatty acid-binding protein (I-FABP) measured in serum (n = 16, 73.9 and 90.5) or in urine (n = 4, 87.9 and 78.9). In assessment of transmural mesenteric ischaemia, urinary I-FABP (n = 2, 92.3 and 85.2) and D-dimer (n = 3, 87.6 and 83.6) showed moderate predictive value. Overall risk of bias was high, mainly because of selected study populations and unclear timings of the biomarker measurements after onset of symptoms. Combinations of biomarkers were rarely studied, not allowing meta-analyses. Conclusions None of the studied biomarkers had sufficient sensitivity and specificity to diagnose AMI, although some biomarkers showed moderate predictive accuracy. Future studies should focus on timing of measurements of biomarkers, distinguishing between early stage and transmural necrosis, and between different types of AMI. Additionally, studies on combinations of biomarkers are warranted. PROSPERO registration: CRD42022379341.

Advancements in materials science and 3D printing technologies have opened up new avenues for developing low-cost robotic grippers with high-performance capabilities, making them suitable for various biomechatronic applications. In this research, it has been explored the utilization of high-performance polymer materials, such as Polyetherketoneketone (PEKK), Polyethylene Terephthalate Glycol (PET-G) and MED 857 (DraftWhite), in the designing and developing of customized robotic grippers. The primary focus of made analyses was oriented on materials characterization, both experimentally and analytically. Computer-Aided Engineering (CAE) methods were employed to simulate bending experiments, allowing for a comprehensive analysis of the mechanical behavior of the selected materials. These simulations were validated through physical bending experiments using samples fabricated via 3D printing technologies, including Fused Filament Fabrication (FFF) for PET-G and PEKK, as well as Jetted Photopolymer (PolyJet) technology employing UV Resin for MED 857. The findings of this research provided advantages of utilizing advanced materials like PEKK in low-cost robotic grippers for biomechatronic applications. The experimental and analytical approaches offer valuable insights into material selection, design optimization, and the development of cost-effective high-performing robotic systems with a wide range of applications in the field of biomechatronics.

A critical infrastructure consists of basic assets and facilities whose functioning has a significant impact on the society and economy of a country, as well as on its security. The life and work of the citizens of a country are largely dependent on a smooth operation of various energy, telecommunication, water and sewage facilities, as well as the network of hospitals and health institutions, transportation, etc. The safe functioning of these systems is a prerequisite for the existence and development of a social community in an area. Therefore, it is necessary to undertake all necessary activities to preserve a critical infrastructure both in reality and cyberspace. With the development of the Internet, there has been a transformation of people’s work and life in the broadest sense, in such a way that it has become an indispensable part of everyday life of each of us. Together with the largest global network increasingly used as well as the various services people necessarily being relied on in the new reality the world encountered during the COVID-10 pandemic, there has been created a vast space attracting the malicious users. They act by using the known mechanisms of functioning communication networks and other information technologies, finding the system vulnerabilities and exploit them. In this paper, we will analyze the cyber security of a critical infrastructure, cyber attacks on a critical infrastructure and the measures needed to be taken to mitigate the consequences of cyber attacks.

Introduction Visuospatial and executive impairments have been associated with poor activity performance sub-acute after stroke. Potential associations long-term and in relation to outcome of rehabilitation interventions need further exploration. Aims To explore associations between visuospatial and executive function and 1) activity performance (mobility, self-care and domestic life) and 2) outcome after 6 weeks of conventional gait training and/or robotic gait training, long term (1–10 years) after stroke. Methods Participants (n = 45), living with stroke affecting walking ability and who could perform the items assessing visuospatial/executive function included in the Montreal Cognitive Assessment (MoCA Vis/Ex) were included as part of a randomized controlled trial. Executive function was evaluated using ratings by significant others according to the Dysexecutive Questionnaire (DEX); activity performance using 6-minute walk test (6MWT), 10-meter walk test (10MWT), Berg balance scale, Functional Ambulation Categories, Barthel Index and Stroke Impact Scale. Results MoCA Vis/Ex was significantly associated with baseline activity performance, long-term after stroke (r = .34-.69, p < .05). In the conventional gait training group, MoCA Vis/Ex explained 34% of the variance in 6MWT after the six-week intervention (p = 0.017) and 31% (p = 0.032) at the 6 month follow up, which indicate that a higher MoCA Vis/Ex score enhanced the improvement. The robotic gait training group presented no significant associations between MoCA Vis/Ex and 6MWT indicating that visuospatial/executive function did not affect outcome. Rated executive function (DEX) presented no significant associations to activity performance or outcome after gait training. Conclusion Visuospatial/executive function may significantly affect activity performance and the outcome of rehabilitation interventions for impaired mobility long-term after stroke and should be considered in the planning of such interventions. Patients with severely impaired visuospatial/executive function may benefit from robotic gait training since improvement was seen irrespective of visuospatial/executive function. These results may guide future larger studies on interventions targeting long-term walking ability and activity performance. Trial registration clinicaltrials.gov (NCT02545088) August 24, 2015.

Objective To estimate the incidence of acute mesenteric ischaemia (AMI), proportions of its different forms and short-term and long-term mortality.Design Systematic review and meta-analysis.Data sources MEDLINE (Ovid), Web of Science, Scopus and Cochrane Library were searched until 26 July 2022.Eligibility criteria Studies reporting data on the incidence and outcomes of AMI in adult populations.Data extraction and synthesis Data extraction and quality assessment with modified Newcastle-Ottawa scale were performed using predeveloped standard forms. The outcomes were the incidence of AMI and its different forms in the general population and in patients admitted to hospital, and the mortality of AMI in its different forms.Results From 3064 records, 335 full texts were reviewed and 163 included in the quantitative analysis. The mean incidence of AMI was 6.2 (95% CI 1.9 to 12.9) per 100 000 person years. On average 5.0 (95% CI 3.3 to 7.1) of 10 000 hospital admissions were due to AMI. Occlusive arterial AMI was the most common form constituting 68.6% (95% CI 63.7 to 73.2) of all AMI cases, with similar proportions of embolism and thrombosis.Overall short-term mortality (in-hospital or within 30 days) of AMI was 59.6% (95% CI 55.5 to 63.6), being 68.7% (95% CI 60.8 to 74.9) in patients treated before the year 2000 and 55.0% (95% CI 45.5 to 64.1) in patients treated from 2000 onwards (p

Objectives We investigated the effectiveness of low-level laser therapy (LLLT) in lower extremity tendinopathy and plantar fasciitis on patient-reported pain and disability.Design Systematic review and meta-analysis.Data sources Eligible articles in any language were identified through PubMed, Embase and Physiotherapy Evidence Database (PEDro) on the 20 August 2020, references, citations and experts.Eligibility criteria for selection of studies Only randomised controlled trials involving participants with lower extremity tendinopathy or plantar fasciitis treated with LLLT were included.Data extraction and synthesis Random effects meta-analyses with dose subgroups based on the World Association for Laser Therapy treatment recommendations were conducted. Risk of bias was assessed with the PEDro scale.Results LLLT was compared with placebo (10 trials), other interventions (5 trials) and as an add-on intervention (3 trials). The study quality was moderate to high.Overall, pain was significantly reduced by LLLT at completed therapy (13.15 mm Visual Analogue Scale (VAS; 95% CI 7.82 to 18.48)) and 4–12 weeks later (12.56 mm VAS (95% CI 5.69 to 19.42)). Overall, disability was significantly reduced by LLLT at completed therapy (Standardised Mean Difference (SMD)=0.39 (95% CI 0.09 to 0.7) and 4–9 weeks later (SMD=0.32 (95% CI 0.05 to 0.59)). Compared with placebo control, the recommended doses significantly reduced pain at completed therapy (14.98 mm VAS (95% CI 3.74 to 26.22)) and 4–8 weeks later (14.00 mm VAS (95% CI 2.81 to 25.19)). The recommended doses significantly reduced pain as an add-on to exercise therapy versus exercise therapy alone at completed therapy (18.15 mm VAS (95% CI 10.55 to 25.76)) and 4–9 weeks later (15.90 mm VAS (95% CI 2.3 to 29.51)). No adverse events were reported.Conclusion LLLT significantly reduces pain and disability in lower extremity tendinopathy and plantar fasciitis in the short and medium term. Long-term data were not available. Some uncertainty about the effect size remains due to wide CIs and lack of large trials.PROSPERO registration number CRD42017077511.

Objective: Metformin is associated with a reduced incidence and growth of abdominal aortic aneurysms (AAAs). The aim of the present study was to investigate the inhibitory effects of metformin on AAA development and possible underlying mechanisms in experimentally induced AAAs in mice, along with the possible synergistic effects of metformin and imatinib. Methods: Angiotensin II was used to induce AAAs in apolipoprotein E knockout (ApoE−/−) mice for 28 days. The mice were treated with metformin (n = 11), metformin combined with imatinib (n = 7), or vehicle (n = 12), starting 3 days before angiotensin II infusion. Ultrasound examination was used to analyze aneurysm formation. Cholesterol and blood pressure levels were measured at the start and end of the study. Gene array and quantitative polymerase chain reaction were used to analyze the changes in gene expression in the aorta. Wire myography was used to study vascular function. Results: Metformin (n = 11) suppressed the formation and progression of AAAs by 50% compared with the vehicle controls (n = 12), with no further effects from imatinib (n = 7). Metformin reduced total cholesterol and mRNA expression of SPP1 (encoding osteopontin), MMP12, and the glycoprotein genes Gpnmb and Clec7a. Furthermore, metformin inhibited blood pressure increases and reduced vascular contractions, as determined by wire myography, and restored the anticontractile function of perivascular adipose tissue. Conclusion: Metformin inhibited aneurysm formation and progression and normalized vascular function in ApoE−/− mice with no additional effect of imatinib. This might be mediated by the protective effects on vascular endothelial function and perivascular adipose tissue via reduced expression of genes promoting inflammation, including SPP1, MMP12, Gpnmb, and Clec7a. Clinical relevance: Retrospective studies of the effects of metformin in patients with aneurysm have so far only been performed of those with type 2 diabetes. The present study shows that metformin has effects on nondiabetic mice and revealed the mechanistic effects mediated by the drug that could also be important to study as outcomes in humans. Future clinical trials using metformin are warranted in patients without diabetes with abdominal aortic aneurysms.

Background: Patients with popliteal artery aneurysm (PA) often have multiple aneurysms, such as bilateral disease or a concomitant abdominal aortic aneurysm (AAA). microRNAs (miRs) are regulators of biological processes and have been investigated as biomarkers for AAA. The aim of this study was to explore if the presence of multiple aneurysms and/or location correlated with miR levels in blood. Methods: Using quantitative polymerase chain reaction, 23 miRs were analyzed in plasma from 183 patients with PA. Results: Fifteen of the miRs were associated with the number and/or location of aneurysms (1.3- to 2.1-fold changes). Levels of miR-93 (1.4-fold) and miR-215 (1.6- to 1.9-fold) were changed in all compared groups. MiR-24 and miR-23a were altered in those with AAA (1.4- and 1.5-fold, respectively) or bilateral PA (1.5- and 1.4-fold, respectively), compared with in those without. MiR-145 were significantly altered (1.7-fold) in those with isolated PA and AAA, whereas miR-326 were altered in those with bilateral (2.3-fold) and isolated PA (1.9-fold). Conclusions: Different miRs seem to be important or to be markers for different subgroups of patients with PA. The identified miRs target vascular smooth muscle cell proliferation and vascular inflammation. Further studies are needed to increase the understanding of the pathogenesis of aneurysmal disease. : Clinical Relevance: Patients with popliteal artery aneurysm often have multiple aneurysms, such as bilateral disease or concomitant abdominal aortic aneurysms, but the molecular pathogenesis of the disease is not fully understood. MicroRNAs are important regulators of gene expression and biological processes and have recently been investigated as possible biomarkers for abdominal aortic aneurysm. This study identified 11 microRNAs that were altered in subgroups of patients with popliteal artery aneurysm, which could be important regulators to study in interventional studies.

Abstract Background The optimal time-response window for photobiomodulation therapy (PBMT) using low-level laser therapy (LLLT) and/or light emitting diodes therapy (LEDT) combined with static magnetic fields (sMF) before physical activity still was not fully investigated. The aim of the present study was to investigate the better of four time-response windows for PBMT combined with sMF (PBMT-sMF) use before exercise in humans. Methods A prospectively registered, randomized, triple-blinded (volunteers, therapists and assessors) placebo-controlled trial was carried out. Sixty healthy untrained male subjects were randomly allocated to six experimental groups (n = 10 per group): PBMT-sMF 5 mins, PBMT-sMF 3 h, PBMT-sMF 6 h, PBMT-sMF 1-day, placebo, and control. The control group performed all procedures, however did not receive any kind of intervention. PBMT-sMF active or PBMT-sMF placebo was applied precisely in different time points after baseline MVC test to ensure that both MVC tests and eccentric exercise protocol would occur at the same hour of the day in all groups. Then, after five minutes, 3 h, 6 h or 1-day (24 h) of PBMT-sMF treatment (active or placebo) the eccentric exercise protocol was performed. The primary outcome was peak torque obtained from maximum voluntary contraction (MVC). The secondary outcomes were creatine kinase (CK), and delayed onset muscle soreness (DOMS). The primary and secondary outcomes were measured at baseline, immediately after, 1 h, 24 h and 48 h after the eccentric exercise protocol. Results Sixty patients were randomized and analyzed to each sequence. The outcomes in absolute values show that all active PBMT-sMF groups increased (p

Abstract Aim To examine the extent to which sex, country of birth, and functional aspects influence participation in physical education and physical leisure activity among children with cerebral palsy (CP) in Sweden. Methods This national cross‐sectional registry study included children with CP aged 6 to 18 years who participated in the Swedish national quality registry, the Cerebral Palsy Follow‐up Program, CPUP, in 2015. Comparisons and associations between sex, country of birth, and functional aspects and physical leisure/physical education were examined using chi‐squared and multivariable logistic regression analysis. Results The study included 1935 children. Of them, 1625 (87%) reported participating in physical education and 989 (53%) reported participating in physical leisure activity. Children born in Sweden had higher odds of participating in physical education (OR: 1.99; 95% CI: 1.20‐3.28) and physical leisure activity (OR: 2.51; 95% CI: 1.70‐3.72) compared with children born outside Europe. Greater impairment of gross motor function was associated with lower participation levels. Boys participated slightly more frequently in leisure activities than girls. Conclusion Enhancing social inclusion with regard to disability, birth country, and sex are important and achievable goals for policymakers and practitioners for promoting participation in physical activity for children and adolescents with CP.

Introduction Shoulder pain affects approximately one in four adults and is thus one of the most common musculoskeletal problems. Only 50% of patients who begin treatment for shoulder pain are cured within 6 months. There is a need for systematic reviews to estimate the effectiveness of shoulder treatments. We decided to evaluate the effect of mobilisation with movement (MWM) on chronic shoulder pain in a systematic review.Methods and analysis The review will include controlled trial articles identified via five electronic databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Central Register of Controlled Trials), reference lists, citations searches and experts in the field. Only controlled trials involving participants with a mean duration of pain of ≥3 months, in which the effectiveness of MWM has been compared with non-invasive treatments, sham mobilisation or wait-and-see will be included. The included trials will be synthesised with random effects meta-analyses. Risk-of-bias will be assessed with the Physiotherapy Evidence Database 0–10 point scale.Ethics and dissemination The review does not require ethics approval as it is based on anonymised data from trial reports. The results of the review will be disseminated through a peer-reviewed publication.PROSPERO registration number CRD42018109380.

Abstract Background Trauma triage based on prehospital information facilitates correct allocation of in-hospital resources. The Swedish national two-tier trauma team activation (TTA) criteria were revised in 2016. The current study aimed to evaluate the safety and efficacy of the new criteria. Methods Five centres covering trauma care for 1.2 million inhabitants registered all trauma patients prospectively in the Swedish trauma registry (SweTrau) prior to and after stepwise introduction of new TTA criteria within the cohort (a prospective stepped-wedge cohort study design; period August 2016–November 2017). Evaluation of full- and limited-TTA frequency, under- and overtriage were performed at equal duration before and after this change. Results The centres registered 1948 patients, 1882 (96.6%) of which were included in the study. With new criteria, frequency of full-TTA was unchanged, while limited-TTA decreased with 46.3% (from 988 to 531). 30-day trauma mortality was unchanged. The overtriage was 107/150 (71.3%) with former criteria, and 104/144 (72.2%) with new criteria, p = 0.866. Undertriage was 50/1037 (4.8%) versus 39/551 (7.1%), p = 0.063. Undertriage was consistently > 20% in patients with fall injury. Among patients with Injury Severity Score (ISS) > 15, 50/93 (53.8%) did not initiate full-TTA with former, vs 39/79 (49.4%) with new criteria, p = 0.565. Age > 60-years was a risk factor for undertriage (OR 2.89, p

Objective To systematically review and summarise the evidence for the effects of neuromuscular training compared with any other therapy (conventional training/sham) on knee proprioception following anterior cruciate ligament (ACL) injury.Design Systematic Review.Data sources PubMed, CINAHL, SPORTDiscus, AMED, Scopus and Physical Education Index were searched from inception to February 2020.Eligibility criteria Randomised controlled trials (RCTs) and controlled clinical trials investigating the effects of neuromuscular training on knee-specific proprioception tests following a unilateral ACL injury were included.Data extraction and synthesis Two reviewers independently screened and extracted data and assessed risk of bias of the eligible studies using the Cochrane risk of bias 2 tool. Overall certainty in evidence was determined using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool.Results Of 2706 articles retrieved, only 9 RCTs, comprising 327 individuals with an ACL reconstruction (ACLR), met the inclusion criteria. Neuromuscular training interventions varied across studies: whole body vibration therapy, Nintendo-Wii-Fit training, balance training, sport-specific exercises, backward walking, etc. Outcome measures included joint position sense (JPS; n=7), thresholds to detect passive motion (TTDPM; n=3) or quadriceps force control (QFC; n=1). Overall, between-group mean differences indicated inconsistent findings with an increase or decrease of errors associated with JPS by ≤2°, TTDPM by ≤1.5° and QFC by ≤6 Nm in the ACLR knee following neuromuscular training. Owing to serious concerns with three or more GRADE domains (risk of bias, inconsistency, indirectness or imprecision associated with the findings) for each outcome of interest across studies, the certainty of evidence was very low.Conclusions The heterogeneity of interventions, methodological limitations, inconsistency of effects (on JPS/TTDPM/QFC) preclude recommendation of one optimal neuromuscular training intervention for improving proprioception following ACL injury in clinical practice. There is a need for methodologically robust RCTs with homogenous populations with ACL injury (managed conservatively or with reconstruction), novel/well-designed neuromuscular training and valid proprioception assessments, which also seem to be lacking.PROSPERO registration number CRD42018107349.

Este documento deve ser referenciado citando também a versão original em Inglês: Björck M, Earnshaw JJ, Acosta S, Bastos Gonçalves F, Cochennec F, Debus ES, Hinchliffe R, Jongkind V, Koelemay MJW, Menyhei G, Svetlikov AV, Tshomba Y, Van Den Berg JC, Esvs Guidelines Committee, de Borst GJ, Chakfé N, Kakkos SK, Koncar I, Lindholt JS, Tulamo R, Vega de Ceniga M, Vermassen F, Document Reviewers, Boyle JR, Mani K, Azuma N, Choke ETC, Cohnert TU, Fitridge RA, Forbes TL, Hamady MS, Munoz A, Müller-Hülsbeck S, Rai K. Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. Eur J Vasc Endovasc Surg. 2020 Feb;59(2):173-218. Epub 2019 Dec 31. PMID: 31899099. Published by Elsevier B.V. on behalf of European Society for Vascular Surgery. https://doi.org/10.1016/j.ejvs.2019.09.006

Langerhans cell histiocytosis (LCH) is an infrequent disease, characterized by oligoclonal proliferation of immature myeloid-derived cells. However, the exact pathogenesis remains unknown. In rare cases, LCH is present in patients with concomitant myeloid proliferative neoplasms. Here, we describe a 69-year-old male, who presented with a maculopapular rash covering truncus, face, and scalp. A cutaneous ulcerating lesion on the right cheek led to a biopsy showing LCH. Lesional cells were BRAFV600E and JAK2V617F mutated. A bone marrow aspirate showed no infiltration of Langerhans cells, but alterations consistent with primary myelofibrosis (PMF) and a polymerase chain reaction test were positive for JAK2V617F. Our case highlights an uncommon condition of two hematological malignancies present in the same patient. The identification of the BRAFV600E mutation supports previous findings of this mutation in LCH. Interestingly, a JAK2V617F mutation was found in both LCH and PMF cells, indicating a possible clonal relationship between the two malignancies.

Abstract We read with interest the article by Gomes et al. entitled: “Exercise program combined with electrophysical modalities in subjects with knee osteoarthritis: A randomised, placebo-controlled clinical trial”. Gomes et al. concluded that the low-level laser therapy (LLLT) did not reduce knee osteoarthritis pain when applied as an adjunct to exercise therapy. We argue that Gomes et al. neglected relevant laser treatment recommendations in the conduct and reporting of the trial. Gomes et al. did not state the Joules per treatment spot applied. We calculated the Joules applied from other laser information in the report and found that it is too low of a dose according to the World Association for Laser Therapy (WALT) guidelines. Furthermore, we have published a meta-analysis of 22 placebo-controlled trials demonstrating a significant difference in pain-relieving effect between doses in adherence and non-adherence to the WALT guidelines. However, neither the WALT guidelines, nor our meta-analysis was mentioned by Gomes et al. Moreover, Gomes et al. did not state whether the output power of the laser device was measured, and this is concerning because in the city of São Paulo, where the trial was conducted, most laser devices have been found to deliver less of a dose than specified by the manufacturers. In summary, we found that the best available evidence regarding effective and ineffective LLLT dosing from systematic reviews was neglected in the conduct and reporting of the trial, and that the laser device may not have been calibrated.

BACKGROUND AND AIMS: Proximal femoral fracture is often associated with long-term residual disability. Quadriceps weakness may be a factor in poor outcome. This study aimed to determine whether training of the quadriceps using electrical stimulation (ES) increases leg extensor power and decreases disability in elderly subjects rehabilitating after fracture. METHODS: A single-blind randomized controlled trial of elderly postsurgical proximal femoral fracture patients, comparing 6 weeks of supplementary electrical stimulation of the quadriceps (15 patients) to usual physiotherapy alone (11 patients). The electrical stimulation on:off duty cycle was 7:23 seconds, with 36 cycles per session, given daily as an in-patient and twice weekly after discharge. The primary outcome measure was change in leg extensor power (Nottingham Power Rig). Functional mobility (Elderly Mobility Scale), disability (Barthel Index) and health status (Nottingham Health Profile) were also measured. RESULTS: There was no significant difference in change in leg extensor power, or any other outcome measure, in the ES group compared to usualcare controls. Fractured leg extensor power increased by 10.9 (standard error of the mean 2.1) Watts at 6 weeks in the ES group compared to 15.3 (5.5) in the controls (mean adjusted difference -3.1, 95% CI -7.8, 1.6 Watts). Only 3 (20%) of the intervention patients tolerated sufficient stimulation intensity to produce repetitive knee extension, while 11 (73%) sustained palpable or visible contractions with no leg movement. CONCLUSION: A 6-week program of electrical stimulation of the quadriceps did not increase leg extensor power, or reduce disability, in elderly patients rehabilitating after surgical fixation of proximal femoral fracture. In many patients local discomfort limited the intensity of electrical stimulation that could be delivered. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is characterized by structural deterioration of the aortic wall, leading to aortic dilation and rupture. The aim was to compare 183 low molecular weight metabolites in AAA patients and aorta-healthy controls and to explore if low molecular weight metabolites are linked to AAA growth. Blood samples were collected from male AAA patients with fast (mean 3.3 mm/year; range 1.3–9.4 mm/year; n = 39) and slow growth (0.2 mm/year; range −2.6–1.1 mm/year; n = 40), and from controls with non-aneurysmal aortas (n = 79). Targeted analysis of 183 metabolites in plasma was performed with AbsoluteIDQ p180 kit. The samples were measured on a QTRAP 4500 coupled to an Agilent 1260 series HPLC. The levels of only four amino acids (histidine, asparagine, leucine, isoleucine) and four phosphatidylcholines (PC.ae.C34.3, PC.aa.C34.2, PC.ae.C38.0, lysoPC.a.C18.2) were found to be significantly lower (p < 0.05) after adjustment for confounders among the AAA patients compared with the controls. There were no differences in the metabolites distinguishing the AAA patients with slow or fast growth from the controls, or distinguishing the patients with slow growth from those with fast growth. The current study describes novel significant alterations in amino acids and phosphatidylcholines metabolism associated with AAA occurrence, but no associations were found with AAA growth rate.

Abstract Background This study systematically summarizes quantitative imaging biomarker research in non-traumatic neck and shoulder musculoskeletal disorders (MSDs). There were two research questions: 1) Are there quantitative imaging biomarkers associated with the presence of neck and shoulder MSDs?, 2) Are there quantitative imaging biomarkers associated with the severity of neck and shoulder MSDs? Methods PubMed and SCOPUS were used for the literature search. One hundred and twenty-five studies met primary inclusion criteria. Data were extracted from 49 sufficient quality studies. Results Most of the 125 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. Only half controlled for potential confounders via exclusion or in the analysis. Approximately one-third reported response rates. In sufficient quality articles, 82% demonstrated at least one statistically significant association between the MSD(s) and biomarker(s) studied. The literature synthesis suggested that neck muscle size may be decreased in neck pain, and trapezius myalgia and neck/shoulder pain may be associated with reduced vascularity in the trapezius and reduced trapezius oxygen saturation at rest and in response to upper extremity tasks. Reduced vascularity in the supraspinatus tendon may also be a feature in rotator cuff tears. Five of eight studies showed an association between a quantitative imaging marker and MSD severity. Conclusions Although research on quantitative imaging biomarkers is still in a nascent stage, some MSD biomarkers were identified. There are limitations in the articles examined, including possible selection bias and inattention to potentially confounding factors. Recommendations for future studies are provided.

Physical activity and low-level laser therapy (LLLT) can reduce knee osteoarthritis (KOA) inflammation. We are conducting a randomized placebo-controlled trial to investigate the long-term effectiveness of LLLT combined with strength training (ST) in persons with KOA, since it, to our knowledge, has not been investigated before. Fifty participants were enrolled. LLLT and ST was performed 3 times per week over 3 and 8 weeks, respectively. In the LLLT group, 3 Joules of 904 nm wavelength laser was applied to 15 spots per knee (45 Joules/knee/session). The primary outcomes are pain during movement, at night and at rest (Visual Analogue Scale) and global pain (Knee injury and Osteoarthritis Outcome Score, KOOS) pain subscale. The secondary outcomes are KOOS disability and quality-of-life, analgesic usage, global health change, knee active range of motion, 30 s chair stand, maximum painless isometric knee extension strength, knee pain pressure threshold and real-time ultrasonography-assessed suprapatellar effusion, meniscal neovascularization and femur cartilage thickness. All the outcomes are assessed 0, 3, 8, 26 and 52 weeks post-randomization, except for global health change, which is only evaluated at completed ST. This study features the blinding of participants, assessors and therapists, and will improve our understanding of what occurs with the local pathophysiology, tissue morphology and clinical status of persons with KOA up to a year after the initiation of ST and a higher 904 nm LLLT dose than in any published trial on this topic.

OBJECTIVE: This study systematically summarizes biochemical biomarker research in non-traumatic musculoskeletal disorders (MSD). Two research questions guided the review: (i) Are there biochemical markers associated with neck and upper-extremity MSD? and (ii) Are there biochemical markers associated with the severity of neck and upper-extremity MSD? METHODS: A literature search was conducted in PubMed and SCOPUS, and 87 studies met primary inclusion criteria. Following a quality screen, data were extracted from 44 articles of sufficient quality. RESULTS: Most of the 87 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. A response rate was explicitly stated in only 11 (13%) studies. Less than half of the studies controlled for potential confounding through restriction or in the analysis. Most sufficient-quality studies were conducted in older populations (mean age in one or more analysis group >50 years). In sufficient-quality articles, 82% demonstrated at least one statistically significant association between the MSD and biomarker(s) studied. Evidence suggested that: (i) the collagen-repair marker TIMP-1 is decreased in fibro proliferative disorders, (ii) 5-HT (serotonin) is increased in trapezius myalgia, and (iii) triglycerides are increased in a variety of MSD. Only 5 studies showed an association between a biochemical marker and MSD severity. CONCLUSION: While some MSD biomarkers were identified, limitations in the articles examined included possible selection bias, confounding, spectrum effect (potentially heterogeneous biomarker associations in populations according to symptom severity or duration), and insufficient attention to comorbid conditions. A list of recommendations for future studies is provided.

This study investigated the use of EMG biofeedback to simulate weakened rectus femorii and gastrocnemii muscles during the performance of a lifting task. Eight healthy women performed 15 kg free-style lifts from floor level. Three conditions were tested: unconstrained lifting, lifting with rectus femorii activity volitionally limited bilaterally through EMG biofeedback to less than 45% of maximal EMG activity, and lifting with the gastrocnemii limited to a similar level. Limiting leg muscle activity through biofeedback led to an alteration of lifting strategy, with resulting performance variables (joint angles and torques, angular velocities, center of pressure excursion, and segment coordination) comparing favorably with those from lifting trials performed by six women with moderate leg muscle weaknesses. The data indicate that EMG biofeedback can be used to simulate the effects of leg muscle weakness during these lifts, providing a new tool to study the biomechanics of muscle weakness. [ABSTRACT FROM AUTHOR]

BackgroundModifiable lifestyle‐related factors associated with risk of abdominal aortic aneurysm (AAA) are rarely investigated with a prospective design. We aimed to study possible associations among such factors and comorbidities with mean abdominal aortic diameter (AAD) and with risk of AAA among men screened for the disease. Methods and ResultsSelf‐reported lifestyle‐related exposures were assessed at baseline (January 1, 1998) among 14 249 men from the population‐based Cohort of Swedish Men, screened for AAA between 65 and 75 years of age (mean 13 years after baseline). Multivariable prediction of mean AAD was estimated with linear regression, and hazard ratios (HRs) of AAA (AAD ≥30 mm) with Cox proportional hazard regression. The AAA prevalence was 1.2% (n=168). Smoking, body mass index, and cardiovascular disease were associated with a larger mean AAD, whereas consumption of alcohol and diabetes mellitus were associated with a smaller mean AAD. The HR of AAA was increased among participants who were current smokers with ≥25 pack‐years smoked compared with never smokers (HR 15.59, 95% CI 8.96–27.15), those with a body mass index ≥25 versus 40 minutes/day (versus almost never) was associated with lower AAA hazard (HR 0.59, 95% CI 0.36–0.97) compared with almost never walking or bicycling. ConclusionsThis prospective study confirms that modifiable lifestyle‐related factors are associated with AAD and with AAA disease.

Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine.Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure.Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour.The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Background. Psychodynamic psychotherapy is a psychological treatment approach that has a growing empirical base. Research has indicated an association between therapist-facilitated affective experience and outcome in psychodynamic therapy. Affect-phobia therapy (APT), as outlined by McCullough et al., is a psychodynamic treatment that emphasizes a strong focus on expression and experience of affect. This model has neither been evaluated for depression nor anxiety disorders in a randomized controlled trial. While Internet-delivered psychodynamic treatments for depression and generalized anxiety disorder exist, they have not been based on APT. The aim of this randomized controlled trial was to investigate the efficacy of an Internet-based, psychodynamic, guided self-help treatment based on APT for depression and anxiety disorders.Methods. One hundred participants with diagnoses of mood and anxiety disorders participated in a randomized (1:1 ratio) controlled trial of an active group versus a control condition. The treatment group received a 10-week, psychodynamic, guided self-help treatment based on APT that was delivered through the Internet. The treatment consisted of eight text-based treatment modules and included therapist contact (9.5 min per client and week, on average) in a secure online environment. Participants in the control group also received online therapist support and clinical monitoring of symptoms, but received no treatment modules. Outcome measures were the 9-item Patient Health Questionnaire Depression Scale (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7). Process measures were also included. All measures were administered weekly during the treatment period and at a 7-month follow-up.Results. Mixed models analyses using the full intention-to-treat sample revealed significant interaction effects of group and time on all outcome measures, when comparing treatment to the control group. A large between-group effect size of Cohen’s d = 0.77 (95% CI: 0.37–1.18) was found on the PHQ-9 and a moderately large between-group effect size d = 0.48 (95% CI: 0.08–0.87) was found on the GAD-7. The number of patients who recovered (had no diagnoses of depression and anxiety, and had less than 10 on both the PHQ-9 and the GAD-7) were at post-treatment 52% in the treatment group and 24% in the control group. This difference was significant, χ2(N = 100, d f = 1) = 8.3, p < .01. From post-treatment to follow-up, treatment gains were maintained on the PHQ-9, and significant improvements were seen on the GAD-7.Conclusion. This study provides initial support for the efficacy of Internet-delivered psychodynamic therapy based on the affect-phobia model in the treatment of depression and anxiety disorders. The results support the conclusion that psychodynamic treatment approaches may be transferred to the guided self-help format and delivered via the Internet.

Introduction: Overuse musculoskeletal injuries (MSKI) remain a significant medical challenge in military personnel undergoing military training courses; further understanding of the biological process leading to overuse MSKI development and biological signatures for injury risk are warranted. The purpose of this study was to determine the association between overuse MSKI occurrence and physiological characteristics of allostatic load characterized as maladaptive biological responses to chronic stress measured by wearable devices in US Marine Corps officer candidates during a 10-wk training course., Methods: Devices recorded energy expenditure (EE), daytime heart rate (HR), sleeping HR, and sleep architecture (time and percentage of deep, light, rapid eye movement sleep, awake time, total sleep). Flux was calculated as the raw or absolute difference in the average value for that day or night and the day or night beforehand. Linear mixed-effect model analysis accounting for cardiorespiratory fitness assessed the association between overuse MSKI occurrence and device metrics ( α = 0.05)., Results: Sixty-nine participants (23 females) were included. Twenty-one participants (eight females) sustained overuse MSKI. Overuse MSKI occurrence in male participants was positively associated with daytime HR ( β = 5.316, P = 0.008), sleeping HR ( β = 2.708, P = 0.032), relative EE ( β = 8.968, P = 0.001), absolute flux in relative EE ( β = 2.994, P = 0.002), absolute EE ( β = 626.830, P = 0.001), and absolute flux in absolute EE ( β = 204.062, P = 0.004). Overuse MSKI occurrence in female participants was positively associated with relative EE ( β = 5.955, P = 0.026), deep sleep time ( β = 0.664, P < 0.001), and percent deep sleep ( β = 12.564, P < 0.001) and negatively associated with absolute flux in sleeping HR ( β = -0.660, P = 0.009)., Conclusions: Overuse MSKI occurrences were associated with physiological characteristics of allostatic load, including chronically elevated HR and EE and greater time in restorative sleep stages, which may serve as biological signatures for overuse MSKI risk., (Copyright © 2024 by the American College of Sports Medicine.)

The objective is to examine the predictors of attrition in male and female candidates undergoing a 10-week early career military training program. 1006 candidates (79.5% male, 24.7 ± 3.2 years) consented to participating in a larger study examining predictors of injury during US Marine Corps Officer Candidates School (OCS). Participants completed a blood draw, demographic and psychological characteristics questionnaires, and two fitness tests. Participants were then grouped based on successful completion of OCS or not. Associations between potential predictors and attrition were analyzed using simple logistic regression analyses, followed by a backward stepwise elimination method. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to determine the accuracy of the attrition prediction model. 260 candidates (25.8%) attritted over the 10-week training, with the highest number of discharges during week 5. Musculoskeletal injury (MSKI) was the most common cause of attrition (30%), followed by non-MSKI medical (21.5%), and volitional withdrawals (19.6%). Sex, body mass index (BMI), resilience, initial physical fitness test score, combat fitness test (CFT) score, and prior military service were all significantly associated with attrition from OCS (all p  < .05). The final prediction model of attrition included CFT score ( p  = .027) and resilience ( p  = .018). Multiple demographic, psychological, and fitness characteristics are associated with attrition from an early career military training course (OCS) and may be utilized as part of early screening procedures to identify and provide guidance for individuals at risk for not completing OCS.