Structural Determinants of Tendon Multiscale Mechanics and Their Sensitivity to Mechanical Stimulation During Development in an Embryonic Chick Model.

There is an abrupt increase in the multiscale mechanical properties and load-bearing capabilities of tendon during embryonic development. While prior work has identified numerous changes that occur within the collagenous structure during this developmental period, the primary structural elements that give rise to this abrupt increase in mechanical functionality, and their mechanobiological sensitivity, remain unclear. To address this knowledge gap, we used a shear lag model along with ultrastructural imaging, biochemical/thermodynamic assays, and multiscale mechanical testing to investigate the dynamic structure-function relationships during late-stage embryonic chick development and to establish their sensitivity to mechanical stimulation. Mechanical testing and modeling suggested the rapid increase in multiscale mechanics can be explained by increases in fibril length, intrafibrillar crosslinking, and fibril area fraction. To partially test this, we inhibited collagen crosslinking during development and observed a drastic reduction in multiscale mechanical behavior that was explained by a reduction in both fibril modulus and length. Using muscle paralysis to investigate mechanosensitivity, we observed a significantly impaired multiscale mechanical response despite minimal changes in fibril diameter and fibril area fraction. Additionally, the shear lag model found a trend toward lower fibril lengths with paralysis and experimental data found decreased crosslinking and fibril modulus values following flaccid paralysis. Together, these data suggest that both intrafibrillar crosslink formation and fibril elongation are critical to the formation of load-bearing capabilities in tenogenesis and are sensitive to mechanical loading. These findings provide critical insights into the biological and structural mechanisms that give rise to tensile load-bearing soft tissue. STATEMENT OF SIGNIFICANCE: Despite prior work investigating the structural and mechanical changes that occur during tendon development, there has not been a comprehensive analysis of how these simultaneous changes in structure and function are connected. In this study, we performed a comprehensive battery of mechanical and structural assessments of embryonic chick tendons and input these data into a shear lag model to estimate the individual importance of each structural change to the tendon mechanical properties. Additionally, we inhibited muscle activity in the embryos to evaluate the impact of mechanical stimulation on these evolving structure-function during tendon development. These data provide insight into the primary structural elements that produce the tensile load-bearing capabilities of tendon, which will inform efforts to produce tissue engineering tendon replacements.

The effect of synthetic grass sports surfaces on the thermal environment: A systematic review.

There are concerns regarding high surface temperatures on synthetic grass sports surfaces influencing the surrounding thermal environment, potentially increasing heat stress and impacting athlete safety. As such, studies have investigated changes to the thermal environment surrounding synthetic grass surfaces in comparison to both natural grass, and synthetic surfaces with different features, but this body of research has not been systematically reviewed. Therefore, this systematic review aimed to (i) determine if there are differences in the thermal environment surrounding synthetic grass surfaces compared with natural grass surfaces, and (ii) determine if there are differences in the thermal environment between different types of synthetic grass surfaces. A systematic review adhering to the PRISMA guidelines was performed. The eligibility criteria required investigations to report at least one of the following environmental parameters on or directly above both a synthetic surface and a comparator group of either natural grass or an alternative synthetic grass surface used in sport: Air temperature, mean radiant temperature, humidity, wind velocity, unified heat stress indices (i.e. wet-bulb-globe temperature and heat index) and/or surface temperature. Twenty-three studies were identified. The only parameters that were consistently higher on synthetic grass compared to natural grass were the air temperature (range: 0.5-1.2 °C) and surface temperature (range: 9.4-33.7 °C), while the mean radiant temperature, humidity, wind velocity and wet-bulb-globe temperature remained similar or required more data to determine if any differences exist. Synthetic grass surfaces consisting of styrene butadiene rubber infill or a shock pad had increased surface temperatures, whereas surfaces with thermoplastic elastomer infill, Cool climate turf fibres or HydroChill had lower surface temperatures. This systematic review has demonstrated that air and surface temperatures can be increased on synthetic sports surfaces, compared to natural grass surfaces. However, it is uncertain whether the differences are enough to increase an individual's heat stress risk and cause concern for athlete safety. While modifications to the turf infill or fibres can reduce synthetic surface temperatures, the effect of these features on the thermal environment as a whole is unclear. This review was prospectively registered with the Open Science Framework (Open Science Framework registration   https://doi.org/10.17605/OSF.IO/BTKGE ).

Experiences and impact of a rural Australian high-risk foot service: A multiple-methods study.

OBJECTIVE: Most podiatry-led high-risk foot services (HRFS) in Australia are located in metropolitan areas or large regional centres. In rural areas, where there are limited specialist services, individuals with diabetes-related foot ulceration are more likely to undergo amputation. This study aimed to explore clinicians' perceptions of a recently implemented HRFS in rural New South Wales, Australia, and compare trends of amputation and hospitalisation prior to and post-implementation of the service. SETTING: Rural HRFS in Tamworth, New South Wales, Australia. PARTICIPANTS: Health professionals working within the HRFS were recruited to participate. DESIGN: This was a multiple-methods study. For the qualitative arm, semi-structured interviews were conducted, which were analysed using a reflexive thematic approach. The quantitative arm of the study utilised a retrospective analytic design which applied an interrupted time series to compare amputation and hospitalisation trends pre- and post-implementation of the HRFS utilising diagnostic and procedural ICD codes. RESULTS: The qualitative arm of the study derived three themes: (1) navigating the divide, (2) rural community and rural challenges and (3) professional identity. Results of the interrupted time series indicate that there was a downward trend in major amputations following implementation of the HRFS; however, this was not statistically significant. CONCLUSION: Clinicians were aware of the inequity in DFD outcomes between rural and metropolitan areas and were committed to improving outcomes, particularly with respect to First Nations peoples. Future research will explore service use and amputation rates in the longer term to further evaluate this specialised multidisciplinary care in a rural community.

The effect of wheelchair cushion properties on the microclimate at the cushion-user interface: A systematic review and meta-analysis.

INTRODUCTION: Pressure injuries are a preventable yet highly prevalent health concern. Wheelchair cushion prescription can have significant implications for wheelchair users' risk of pressure injury development, which can impact functional abilities and quality of life. The efficacy of a wheelchair cushion to redistribute pressure has been well-researched, but the efficacy to manage the microclimate is less clear, particularly in warm-hot environments. The aim of this study was to systematically review studies examining the effect of wheelchair cushions on temperature, moisture and thermal perception to determine which cushions are superior to improve these responses. METHOD: A systematic review with meta-analyses of randomised cross-over and randomised control trials of wheelchair cushion interventions on measures of temperature, moisture, and thermal perception was conducted. RESULTS: Eight studies were identified that met the eligibility criteria and six meta-analyses were conducted. Pooled analyses identified a significantly lower temperature on foam-gel cushions compared to air cushions (MD = 0.80, 95% CI: 0.31, 1.29; p = 0.002) and a significantly lower temperature on foam-gel cushions compared to foam cushions (SMD = 0.76, 95%CI; 0.45, 1.06; p < 0.00001). Pooled analyses also demonstrated significantly lower relative humidity (i.e., moisture) on foam cushions compared to foam-gel cushions (p = 0.02). Differences in thermal perception were inconclusive due to limited data found. CONCLUSION: It is clear that not one cushion is ideal in managing all aspects of microclimate, as foam-gel cushions were the superior cushion to manage temperature and foam cushions were the superior cushion to manage moisture. This article provides occupational therapists and other health professionals with evidence-based information to assist with wheelchair cushion prescription that minimises the temperature and moisture accumulation, and associated risk of pressure injury for wheelchair users.

Maximal Lower Limb Strength in Patellar Tendinopathy: A Systematic Review With Meta-Analysis.

OBJECTIVE: To investigate whether lower limb strength is reduced in people with patellar tendinopathy (PT) compared with asymptomatic control individuals or the asymptomatic contralateral limb. DATA SOURCES: MEDLINE, PubMed, Scopus, and Web of Science. STUDY SELECTION: To be included in the systematic review and meta-analysis, studies were required to be peer reviewed, published in the English language, and case control investigations; include participants with a clinical diagnosis of PT and an asymptomatic control or contralateral limb group; and include an objective measure of lower limb maximal strength. DATA EXTRACTION: We extracted descriptive statistics for maximal strength for the symptomatic and asymptomatic limbs of individuals with PT and the limb(s) of the asymptomatic control group, inferential statistics for between-groups differences, participant characteristics, and details of the strength-testing protocol. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool for analytical cross-sectional studies. DATA SYNTHESIS: Of the 23 included studies, 21 reported knee strength, 3 reported hip strength, and 1 reported ankle strength. Random-effects models (Hedges g) were used to calculate the pooled effect sizes (ESs) of muscle strength according to the direction of joint movement and type of contraction. The pooled ESs (95% CI) for maximal voluntary isometric contraction knee-extension strength, concentric knee-extension strength, and concentric knee-flexion strength were 0.54 (0.27, 0.80), 0.78 (0.30, 1.33), and 0.41 (0.04, 0.78), respectively, with all favoring greater strength in the asymptomatic control group. Researchers of 2 studies described maximal eccentric knee-extensor strength with no differences between the PT and asymptomatic control groups. In 3 studies, researchers measured maximal hip strength (abduction, extension, and external rotation), and all within-study ESs favored greater strength in the asymptomatic control group. CONCLUSIONS: Isometric and concentric knee-extensor strength are reduced in people with PT compared with asymptomatic control individuals. In contrast, evidence for reduced eccentric knee-extension strength in people with PT compared with asymptomatic control individuals is limited and inconsistent. Although evidence is emerging that both knee-flexion and hip strength may be reduced in people with PT, more examination is needed to confirm this observation.

Metabolically diverse microorganisms mediate methylmercury formation under nitrate-reducing conditions in a dynamic hydroelectric reservoir.

Brownlee Reservoir is a mercury (Hg)-impaired hydroelectric reservoir that exhibits dynamic hydrological and geochemical conditions and is located within the Hells Canyon Complex in Idaho, USA. Methylmercury (MeHg) contamination in fish is a concern in the reservoir. While MeHg production has historically been attributed to sulfate-reducing bacteria and methanogenic archaea, microorganisms carrying the hgcA gene are taxonomically and metabolically diverse and the major biogeochemical cycles driving mercury (Hg) methylation are not well understood. In this study, Hg speciation and redox-active compounds were measured throughout Brownlee Reservoir across the stratified period in four consecutive years (2016-2019) to identify the location where and redox conditions under which MeHg is produced. Metagenomic sequencing was performed on a subset of samples to characterize the microbial community with hgcA and identify possible links between biogeochemical cycles and MeHg production. Biogeochemical profiles suggested in situ water column Hg methylation was the major source of MeHg. These profiles, combined with genome-resolved metagenomics focused on hgcA-carrying microbes, indicated that MeHg production occurs in this system under nitrate- or manganese-reducing conditions, which were previously thought to preclude Hg-methylation. Using this multidisciplinary approach, we identified the cascading effects of interannual variability in hydrology on the redox status, microbial metabolic strategies, abundance and metabolic diversity of Hg methylators, and ultimately MeHg concentrations throughout the reservoir. This work expands the known conditions conducive to producing MeHg and suggests that the Hg-methylation mitigation efforts by nitrate or manganese amendment may be unsuccessful in some locations.

The effect of cooling garments to improve physical function in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: There is strong evidence for the benefits of exercise for people with Multiple Sclerosis (MS), however, up to 80% of people with MS report experiencing exacerbated symptoms with elevated body temperatures. A range of cooling garments to assist people with MS manage symptoms of heat sensitivity have been investigated. Therefore, the aim of this systematic review was to assess the effect of cooling garments to improve physical function in people with MS, and to determine any associated physiological and perceptual responses. METHOD: A systematic review adhering to the PRISMA guidelines was performed. The eligibility criteria required investigations to have conducted a randomized controlled trial or cross-over study to assess the effect of a cooling garment to improve physical function, or a related physiological or perceptual measure, in people with MS. RESULTS: Thirteen empirical studies were identified, compromising of acute cross-over designs (61.5%), longitudinal parallel group designs (23.1%) or a combination of both (15.4%). The studies included 384 participants with MS with an expanded disability status scale range of 1-7.5. Garments included liquid-perfused cooling vests/tops/hoods (50.0%), phase-change cooling vests (38.9%), a cooling thigh-cuff (5.6%) and a palm cooling device (5.6%). The cooling garments were effective at improving walking capacity and functional mobility, and some studies demonstrated improvements in muscular strength and balance, but not manual dexterity. The garments also resulted in improved core temperature, skin temperature, thermal sensation and subjective fatigue. Improvements occurred in temperate and warm conditions, and both with and without an exercise stimulus. DISCUSSION: Cooling garments can improve physical function for people with MS. Since none of the cooling garments caused harm, and no particular cooling garment could be identified as being superior, people with MS should experiment with different cooling garments to determine their preference, and industry should focus on cooling garments that are effective, accessible and user-friendly.

Nanoparticle-Decorated Biomimetic Extracellular Matrix for Cell Nanoencapsulation and Regulation.

Cell encapsulation has been studied for various applications ranging from cell transplantation to biological production. However, current encapsulation technologies focus on cell protection rather than cell regulation that is essential to most if not all cell-based applications. Here we report a method for cell nanoencapsulation and regulation using an ultrathin biomimetic extracellular matrix as a cell nanocapsule to carry nanoparticles (CN2 ). This method allows high-capacity nanoparticle retention at the vicinity of cell surfaces. The encapsulated cells maintain high viability and normal metabolism. When gold nanoparticles (AuNPs) are used as a model to decorate the nanocapsule, light irradiation transiently increases the temperature, leading to the activation of the heat shock protein 70 (HSP70) promoter and the regulation of reporter gene expression. As the biomimetic nanocapsule can be decorated with any or multiple NPs, CN2 is a promising platform for advancing cell-based applications.

Environmental formation of methylmercury is controlled by synergy of inorganic mercury bioavailability and microbial mercury-methylation capacity.

Methylmercury (MeHg) production is controlled by the bioavailability of inorganic divalent mercury (Hg(II)i ) and Hg-methylation capacity of the microbial community (conferred by the hgcAB gene cluster). However, the relative importance of these factors and their interaction in the environment remain poorly understood. Here, metagenomic sequencing and a full-factorial MeHg formation experiment were conducted across a wetland sulfate gradient with different microbial communities and pore water chemistries. From this experiment, the relative importance of each factor on MeHg formation was isolated. Hg(II)i bioavailability correlated with the dissolved organic matter composition, while the microbial Hg-methylation capacity correlated with the abundance of hgcA genes. MeHg formation responded synergistically to both factors. Notably, hgcA sequences were from diverse taxonomic groups, none of which contained genes for dissimilatory sulfate reduction. This work expands our understanding of the geochemical and microbial constraints on MeHg formation in situ and provides an experimental framework for further mechanistic studies.

Intensity of Lipid-Lowering Therapy Among Patients With Polyvascular Disease.

This cohort study assesses patterns in treatment of low-density lipoprotein cholesterol using lipid-lowering therapy among patients with and without polyvascular disease.

Measurement and reporting of footwear characteristics in running biomechanics: A systematic search and narrative synthesis of contemporary research methods.

This review aimed to synthesise the methods for assessing and reporting footwear characteristics among studies evaluating the effect of footwear on running biomechanics. Electronic searches of Scopus®, EBSCO, PubMed®, ScienceDirect®, and Web of Science® were performed to identify original research articles of the effect of running footwear on running biomechanics published from 1st January 2015 to 7th October 2020. Risk of bias among included studies was not assessed. Results were presented via narrative synthesis. Eligible studies compared the effect of two or more footwear conditions in adult runners on a biomechanical parameter. Eighty-seven articles were included and data from 242 individual footwear were extracted. Predominantly, studies reported footwear taxonomy (i.e., classification) and manufacturer information, however omitted detail regarding the technical specifications of running footwear and did not use validated footwear reporting tools. There is inconsistency among contemporary studies in the methods by which footwear characteristics are assessed and reported. These findings point towards a need for consensus regarding the reporting of these characteristics within biomechanical studies to facilitate the conduct of systematic reviews and meta-analyses pertaining to the effect of running footwear on running biomechanics.

A consensus protocol for the recovery of mercury methylation genes from metagenomes.

Mercury (Hg) methylation genes (hgcAB) mediate the formation of the toxic methylmercury and have been identified from diverse environments, including freshwater and marine ecosystems, Arctic permafrost, forest and paddy soils, coal-ash amended sediments, chlor-alkali plants discharges and geothermal springs. Here we present the first attempt at a standardized protocol for the detection, identification and quantification of hgc genes from metagenomes. Our Hg-cycling microorganisms in aquatic and terrestrial ecosystems (Hg-MATE) database, a catalogue of hgc genes, provides the most accurate information to date on the taxonomic identity and functional/metabolic attributes of microorganisms responsible for Hg methylation in the environment. Furthermore, we introduce "marky-coco", a ready-to-use bioinformatic pipeline based on de novo single-metagenome assembly, for easy and accurate characterization of hgc genes from environmental samples. We compared the recovery of hgc genes from environmental metagenomes using the marky-coco pipeline with an approach based on coassembly of multiple metagenomes. Our data show similar efficiency in both approaches for most environments except those with high diversity (i.e., paddy soils) for which a coassembly approach was preferred. Finally, we discuss the definition of true hgc genes and methods to normalize hgc gene counts from metagenomes.

Factors influencing diabetes-related foot ulcer healing in Australian adults: A prospective cohort study.

OBJECTIVE: Diabetes-related foot ulceration (DFU) is a common limb-threatening condition, which is complex and subsequently challenging to manage. The aim of this study was to determine the contribution of a range of clinical and social factors to the healing of diabetes-related foot ulceration in an Australian population. RESEARCH DESIGN AND METHODS: This was a prospective cohort study of individuals with diabetes-related foot ulceration (DFU). Age, sex, medical history, medications, dietary supplementation (e.g. vitamin C intake) and smoking history were elicited at baseline. The index of relative socio-economic disadvantage (IRSD) was calculated. The Australian Eating Survey and International Physical Activity Questionnaire-short were administered. Wound history, size, grade, time to healing and infection were captured and monitored over 6 months. Logistic regression was performed to determine the relationship between healing and diet quality, toe systolic pressure, wound size at, IRSD, infection and previous amputation. RESULTS: A total of 117 participants were included. The majority were male n = 96 (82%), socio-economically disadvantaged (mean IRSD 965, SD 60), and obese (BMI 36 kg/m2 , SD 11) with a long history of diabetes (20 years, SD 11). Wounds were predominantly neuropathic (n = 85, 73%) and classified 1A (n = 63, 54%) on the University of Texas wound classification system with few infections (n = 23, 16%). Dietary supplementation was associated with 4.36 increased odds of healing (95% 1.28-14.84, p = 0.02), and greater levels of socio-economic advantage were also associated with increased odds of healing (OR 1.01, 95% CI 1.01-1.02, p = 0.03). CONCLUSIONS: In this cohort study of predominantly neuropathic, non-infected DFU, individuals who had greater levels of socio-economic advantage had significantly greater odds of DFU healing. Diet quality was poor in most participants, with individuals taking supplementation significantly more likely to heal.

Going their own way-male recreational runners and running-related injuries: A qualitative thematic analysis.

OBJECTIVE: Recreational running is one of the most common physical leisure activities worldwide and is associated with high rates of running related injury (RRI). Little is known of the perceptions of male recreational runners regarding the aetiology and management of RRI. DESIGN: Utilising an interpretive phenomenological analysis framework, qualitative data was gathered from participants via interview, and reflexive thematic analysis was used to develop insights into the experiences and perceptions of the participants in relation to RRI. MATERIALS AND METHODS: Two focus groups with a total of six (mean age 37.8 ± 9.5 years, 16.5 ± 13.1 years running experience) male recreational runners were used to obtain data regarding their understanding of RRI causation, prevention and management. Interviews were evaluated using a six-phase reflexive thematic analysis approach to generate and interpret themes within the data. RESULTS: Three themes (Mind, Body and Education) were identified by the analysis as critical to RRI avoidance. Mind refers to the self-understanding and self-management of personal limits required for RRI prevention. Body reflects a degree of physical conditioning necessary for injury free running, while Education indicates an understanding of how to correctly structure a running program. When viewed together these themes can be seen to form an 'internal locus of injury' model which highlights the runners' beliefs that RRI are related to their decisions regarding training and running, and that avoidance of injury lies within their personal control. CONCLUSION: Recreational runners rely on self-management, in preference to professional advice, to manage training loads, fitness and RRI. Health care professionals involved with this population may consider the use of online resources, a preferred option of runners, to assist runners to build their knowledge base and support their development to experienced runners.

Outcomes of participation in parkrun, and factors influencing why and how often individuals participate: A systematic review of quantitative studies.

The primary objective of this systematic review was to synthesise peer-reviewed quantitative research of outcomes associated with participation in parkrun. The secondary objective was to synthesise the quantitative research of factors influencing why, and how often, individuals participate in parkrun. Studies were identified via electronic search of Medline, AMED, CINAHL, Cochrane Library, Informit, PsychInfo, SportDiscus, and Web of Science, to 30 March 2021. Two reviewers independently assessed methodological quality. Eleven studies (18,203 participants) were included. Limited evidence from pre-post measure single-group prospective studies suggests parkrun participation promotes improvements in fitness, body mass index, physical activity levels, mood, and personal wellbeing. Individuals with non-running backgrounds generally had higher levels of participation. The main motivators to participate were to improve fitness and social interaction. Future attendance was most strongly correlated with historical attendance. There is a small evidence base for improvements in broad measures of physical and mental health from participation in parkrun. In addition, the study found improving physical fitness and social wellbeing were the main self-reported factors for participation in parkrun. Further research is needed to strengthen the knowledge base of the effects of parkrun to determine its efficacy as a health intervention strategy for physical and mental health.

Cutaneous microvascular reactivity in Charcot neuroarthropathy: a systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the literature investigating the relationship between cutaneous microvascular reactivity in the foot of adults with diabetes-related Charcot neuroarthropathy compared to a non-Charcot adult control group. METHODS: A systematic search was conducted to June 2021 using the biomedical databases EBSCO Megafile Ultimate, Cochrane Library and EMBASE. Original research conducting comparative investigation of cutaneous microvascular reactivity in the foot of adults with diabetes and any pattern of acute or chronic Charcot neuroarthropathy and any non-Charcot adult control groups were included. A modified Critical Appraisal Skills Programme tool was used for quality appraisal. Cutaneous microvascular reactivity in diabetes-related Charcot neuroarthropathy data were synthesised and meta-analysis conducted where possible. RESULTS: The search strategy identified 1,684 articles, with seven eligible for inclusion. Included studies used various methodologies and equipment to assess cutaneous microvascular reactivity in 553 participants (162 with Charcot neuroarthropathy). Cutaneous microvascular reactivity in Charcot neuroarthropathy groups was impaired compared to uncomplicated diabetes groups. Meta-analysis investigating the difference in response to thermal hyperaemia demonstrated a significant difference in cutaneous microvascular reactivity between Charcot neuroarthropathy and peripheral neuropathy with a large, pooled effect size (SMD 1.46 95% CI: 0.89-2.02) and low heterogeneity (I2 = 4%, T2 = 0.01) indicating that the cutaneous microvascular response is more impaired in peripheral neuropathy than in Charcot neuroarthropathy. CONCLUSIONS: Charcot neuroarthropathy is associated with greater cutaneous microvascular reactivity in the periphery relative to diabetes cohorts with diabetes-related peripheral neuropathy alone. It is unknown if this occurs prior to, or as a result of, Charcot neuroarthropathy.

Treatment With Icosapent Ethyl to Reduce Ischemic Events in Patients With Prior Percutaneous Coronary Intervention: Insights From REDUCE-IT PCI.

Background Patients who undergo percutaneous coronary intervention (PCI) are at increased risk for recurrent cardiovascular events despite aggressive medical therapy. Methods and Results This post hoc analysis focused on the subset of patients with prior PCI enrolled in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, randomized, double-blind, placebo-controlled trial of icosapent ethyl versus placebo. Icosapent ethyl was added to statins in patients with low-density lipoprotein cholesterol <100 mg/dL and fasting triglycerides 135-499 mg/dL. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. There were 8179 patients randomized in REDUCE-IT followed for a median of 4.9 years, and 3408 (41.7%) of them had a prior PCI with a median follow-up of 4.8 years. These patients were randomized a median of 2.9 years (11 days to 30.7 years) after PCI. Among patients treated with icosapent ethyl versus placebo, there was a 34% reduction in the primary composite end point (hazard ratio [HR], 0.66; 95% CI, 0.58-0.76; P<0.001; number needed to treat4.8 years=12) and a 34% reduction in the key secondary composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR, 0.66; 95% CI, 0.56-0.79; P<0.001; NNT4.8 years=19) versus placebo. Similarly, large reductions occurred in total coronary revascularizations and revascularization subtypes. There was also a 39% reduction in total events (rate ratio, 0.61; 95% CI, 0.52-0.72; P<0.001). Conclusions Among patients treated with statins with elevated triglycerides and a history of prior PCI, icosapent ethyl substantially reduced the risk of recurrent events during an average of ~5 years of follow-up with a number needed to treat of only 12. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Biomechanical and Musculoskeletal Measurements as Risk Factors for Running-Related Injury in Non-elite Runners: A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND: Running-related injury (RRI) is highly prevalent among recreational runners and is a key barrier to participation. Atypical lower limb alignment and mechanical function have been proposed to play a role in development of lower extremity injury. The purpose of this study was to investigate relationships between incidence of running-related injury (RRI) in non-elite runners with biomechanical and musculoskeletal variables. METHODS: A systematic review and meta-analysis of prospective studies. Published research indexed in MEDLINE, EMBASE, CINAHL, SPORTDiscus, AMED, and The Cochrane library until 13th January 2021, grey literature, and reference lists of included studies were screened to identify prospective studies of non-elite adult runners that measured a relationship between biomechanical or musculoskeletal measures and incidence of RRI. RESULTS: Thirty studies (3404 runners), testing over 100 discrete biomechanical and musculoskeletal risk factors for RRI, were included. Nineteen studies were pooled in twenty-five separate meta-analyses. Meta-analysis of four studies detected significantly less knee extension strength among runners who developed a RRI (SMD - 0.19, 95% CI - 0.36 to - 0.02, p = 0.03), though this may not be clinically important. A meta-analysis of two studies detected significantly lower hip adduction velocity among runners who developed a RRI (MD - 12.80, 95% CI - 25.22 to - 0.38, p = 0.04). Remaining meta-analyses found no significant relationship between biomechanical or musculoskeletal variables and RRI. CONCLUSION: This systematic review and meta-analysis found the currently available literature does not generally support biomechanical or musculoskeletal measures as risk factors for RRI in non-elite runners. While meta-analysis findings for knee extension strength and hip adduction velocity as risk factors for RRI were statistically significant, the associated trivial to small effects sizes suggest these findings should be treated with caution. Until further evidence emerges, recommendations for injury prevention in non-elite runners cannot be made based on biomechanical and musculoskeletal measurements alone.

Effect of Platelet Inhibition by Cangrelor Among Obese Patients Undergoing Coronary Stenting: Insights From CHAMPION.

BACKGROUND: In randomized trials, cangrelor reduced periprocedural ischemic events related to percutaneous coronary intervention without increasing GUSTO severe bleeding. However, some antiplatelet agents have shown a differential treatment effect by body mass index (BMI). METHODS: Patients from the 3 CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) who were randomized to cangrelor versus clopidogrel during percutaneous coronary intervention were stratified by BMI. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis within 48 hours. The principal safety outcome was GUSTO moderate or severe bleeding at 48 hours, although more sensitive bleeding measures such as Thrombolysis in Myocardial Infarction major bleeding were also assessed. We examined obese patients (defined as BMI≥30) versus nonobese patients. RESULTS: There were 24 893 patients, with 8979 (36.1%) having BMI of ≥30. There was no significant difference in the primary efficacy end point among obese versus nonobese patients (4.3% versus 4.2%; rate ratio, 1.01 [95% CI, 0.89-1.15]; P=0.82). There was a consistent benefit in the primary efficacy end point in patients who received cangrelor versus placebo who were obese (3.9% versus 4.7%, rate ratio, 0.83 [95% CI, 0.68-1.02]; P=0.07) and not obese (3.8% versus 4.7%; rate ratio, 0.81 [95% CI, 0.69-0.94]; P=0.0053); interaction P=0.77. There was no difference in GUSTO moderate or severe bleeding among patients who received cangrelor versus placebo who were obese (0.6% versus 0.6%; rate ratio, 0.99 [95% CI, 0.58-1.67]; P=0.96). CONCLUSIONS: Cangrelor at the time of percutaneous coronary intervention is effective and safe in obese and nonobese patients. There was no difference in short-term efficacy between obese and nonobese patients. Periprocedural cangrelor is an effective and safe antiplatelet agent, irrespective of BMI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01156571, NCT00385138, NCT00305162.

Factors influencing lower extremity amputation outcomes in people with active foot ulceration in regional Australia: A retrospective cohort study.

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01-1.03), increased geographical distance (1 km) from HRFS (OR 1.006, 95% CI 1.001-1.01) infection (OR 2.08, 95% CI 1.06-4.07) and presence of diabetes (OR 3.77, 95% CI 1.12-12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.