Moderate- and High-Speed Treadmill Running Exercise Have Minimal Impact on Rat Achilles Tendon.

Exercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches.

Suspended Tissue Open Microfluidic Patterning (STOMP).

Cell-laden hydrogel constructs suspended between pillars are powerful tools for modeling tissue structure and physiology, though current fabrication techniques often limit them to uniform compositions. In contrast, tissues are complex in nature with spatial arrangements of cell types and extracellular matrices. Thus, we present Suspended Tissue Open Microfluidic Patterning (STOMP), which utilizes a removable, open microfluidic patterning channel to pattern multiple spatial regions across a single suspended tissue.

Focal adhesion kinase regulates tendon cell mechanoresponse and physiological tendon development.

Tendons enable locomotion by transmitting high tensile mechanical forces between muscle and bone via their dense extracellular matrix (ECM). The application of extrinsic mechanical stimuli via muscle contraction is necessary to regulate healthy tendon function. Specifically, applied physiological levels of mechanical loading elicit an anabolic tendon cell response, while decreased mechanical loading evokes a degradative tendon state.

A comparison of cenobamate with other newer antiseizure medications for adjunctive treatment of focal-onset seizures: A systematic review and network meta-analysis.

Purpose: To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide, perampanel, and zonisamide, approved for adjunctive treatment of drug-resistant focal-onset seizures (FOS) in adults with epilepsy.

Methods: A systematic literature review (SLR) was conducted to obtain relevant efficacy, safety, and tolerability data for ASMs for the treatment of drug-resistant FOS. All studies were thoroughly assessed for potential sources of heterogeneity and analysed via Bayesian network meta-analyses (NMAs).

The role of quantitative bias analysis for nonrandomized comparisons in health technology assessment: recommendations from an expert workshop.

The use of treatment effects derived from nonrandomized studies (NRS) in health technology assessment (HTA) is growing. NRS carry an inherently greater risk of bias than randomized controlled trials (RCTs). Although bias can be mitigated to some extent through appropriate approaches to study design and analysis, concerns around data availability and quality and the absence of randomization mean residual biases typically render the interpretation of NRS challenging.

Long-Term Effects of Reproduction and Lactation on the Rat Supraspinatus Tendon and Proximal Humerus.

During pregnancy and breastfeeding, women undergo hormonal fluctuations required for fetal development, parturition, and infant growth. These changes have secondary consequences on the maternal musculoskeletal system, increasing the risk for joint pain and osteoporosis. Though hormone levels return to prepregnancy levels postpartum, women may experience lasting musculoskeletal pain.

Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz.

Cells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function are not well understood. Here, we show using a model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs, resulting in subsequent weakening of the tendon.

Investigating the temporal roles of decorin and biglycan in tendon healing.

The small leucine-rich proteoglycans, decorin and biglycan, are minor components of the tendon extracellular matrix that regulate fibrillogenesis and matrix assembly. Our study objective was to define the temporal roles of decorin and biglycan during tendon healing using inducible knockout mice to include genetic knockdown at specific phases of healing: time of injury, the proliferative phase, and the remodeling phase. We hypothesized that knockdown of decorin or biglycan would adversely affect tendon healing, and that by prescribing the timing of knockdown, we could elucidate the temporal roles of these proteins during healing.

Application of quantitative bias analysis for unmeasured confounding in cost-effectiveness modelling.

Due to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomized studies when considering new technologies. Quantitative bias analysis (QBA) methods provide a means to quantify this uncertainty but have not been widely used in the HTA setting, particularly in the context of cost-effectiveness modelling (CEM). This study demonstrated the application of an aggregate and patient-level QBA approach to quantify and adjust for unmeasured confounding in a simulated nonrandomized comparison of survival outcomes.

Unmeasured confounding in nonrandomized studies: quantitative bias analysis in health technology assessment.

Evidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence, as it may result in biased treatment effect estimates, which has led to much criticism of NRS by HTA agencies. Quantitative bias analyses are a group of methods that have been developed in the epidemiological literature to quantify the impact of unmeasured confounding and adjust effect estimates from NRS.

The value of innovation: association between improvements in survival of advanced and metastatic non-small cell lung cancer and targeted and immunotherapy.

Background: Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns.

CHADS-VASc and HAS-BLED risk scores and real-world oral anticoagulant prescribing decisions in atrial fibrillation.

Guidelines indicate that oral anticoagulant (OAC) treatment decisions in atrial fibrillation should be based on a balanced consideration of thromboembolic and bleeding risk. A retrospective cohort of nonvalvular atrial fibrillation patients were identified. Univariate logistic regression and conditional inference trees were used to quantify the importance of the CHADS-VASc and modified HAS-BLED scores and their individual components on OAC treatment decisions.

Derivation of DO-BITS, a score for predicting success on : a retrospective, observational cohort study.

Objective: To derive a score for finishing in the top three positions of the television show, , UK.

Design: A retrospective study was undertaken using data from all previous contestants.

Results: A score predicting show success termed DO-BITS (different coupling approaches [islanders pursuing one or many people on the show], Original islander [being on the show from the start], [being] Brunette, [having] intimate relationships on screen, Tradesman [occupation before being on the show] and Short name [having a four-letter first name]) was developed.

The use of UK primary care databases in health technology assessments carried out by the National Institute for health and care excellence (NICE).

Background: Real world evidence (RWE) is becoming more frequently used in technology appraisals (TAs). This study sought to explore the use and acceptance of evidence from primary care databases, a key source of RWE in the UK, in National Institute for Health and Care Excellence (NICE) technology assessments and to provide recommendations regarding their use in future submissions.

Methods: A keyword search was conducted relating to the main primary care databases in the UK on the NICE website.

Approaches for the identification of chronic kidney disease in CPRD-HES-linked studies.

There are different methods to identify chronic kidney disease (CKD) in Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES). Using CPRD-HES, nonvalvular atrial fibrillation patients were classified according to CKD category. Using glomerular filtration rate/estimated glomerular filtration rate tests only to identify patients with CKD resulted in 3.

Nonindependence of patient data in the clinical practice research datalink: a case study in atrial fibrillation patients.

The impact of different strategies to handle patients with data recorded under multiple Clinical Practice Research Datalink (CPRD) identifiers (IDs) is unknown. Six approaches to handling patients appearing under multiple CPRD IDs were defined. The impact of the approaches was illustrated using a case study describing the clinical characteristics of a population of nonvalvular atrial fibrillation patients.