Association of intra-articular injection and knee arthroscopy prior to primary knee replacement with the timing and outcomes of surgery: Retrospective cohort study using data from the Clinical Practice Research Datalink GOLD database.

Background: Patients with symptomatic knee osteoarthritis may undergo non-surgical interventions such as intra-articular steroid injections and knee arthroscopy. This study aimed to investigate their association with the timing and outcomes of subsequent primary knee replacement.

Methods And Findings: Observational retrospective analysis of linked Clinical Practice Research Datalink, Hospital Episode Statistics, Patient Reported Outcome Measures (CPRD GOLD-HES-PROMS) data of 38,494 patients undergoing primary knee replacements in England.

Recent Electrochemical Advancements for Liquid-Biopsy Nucleic Acid Detection for Point-of-Care Prostate Cancer Diagnostics and Prognostics.

Current diagnostic and prognostic tests for prostate cancer require specialised laboratories and have low specificity for prostate cancer detection. As such, recent advancements in electrochemical devices for point of care (PoC) prostate cancer detection have seen significant interest. Liquid-biopsy detection of relevant circulating and exosomal nucleic acid markers presents the potential for minimally invasive testing.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

Background And Objectives: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak.

The effect of nodal connectivity and strut density within stochastic titanium scaffolds on osteogenesis.

Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular interest as they mimic the architecture of trabecular bone and can combine isotropic properties and adjustable structure. The existing research mainly concentrates on controlling the mechanical and biological performance of periodic lattices by adjusting pore size and shape.

Developing a Natural History Model for Duchenne Muscular Dystrophy.

Background: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD.

Methods: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice.

Natural history of Duchenne muscular dystrophy in the United Kingdom: A descriptive study using the Clinical Practice Research Datalink.

Background: Duchenne muscular dystrophy (DMD) is a rare, muscle-degenerative disease predominantly affecting males. Natural history models capture the full disease pathway under current care and combine with estimates of new interventions' effects to assess cost-effectiveness by health technology decision-makers. These models require mortality estimates throughout a patient's lifetime, but rare disease datasets typically contain relatively few patients with short follow-ups.

Incorporation of patient and public involvement in statistical methodology research: development of an animation.

Background: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects.

Modeling the multi-state natural history of rare diseases with heterogeneous individual patient data: A simulation study.

Multi-state survival models are used to represent the natural history of a disease, forming the basis of a health technology assessment comparing a novel treatment to current practice. Constructing such models for rare diseases is problematic, since evidence sources are typically much sparser and more heterogeneous. This simulation study investigated different one-stage and two-stage approaches to meta-analyzing individual patient data (IPD) in a multi-state survival setting when the number and size of studies being meta-analyzed are small.

Incorporation of patient and public involvement in statistical methodology research: a survey assessing current practices and attitudes of researchers.

Background: Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area.

Handheld ISFET Lab-on-Chip detection of TMPRSS2-ERG and AR mRNA for prostate cancer prognostics.

Ion-sensitive field-effect transistors (ISFETs) in combination with unmodified complementary metal oxide semiconductors present a point-of-care platform for clinical diagnostics and prognostics. This work illustrates the sensitive and specific detection of two circulating mRNA markers for prostate cancer, the androgen receptor and the TMPRSS2-ERG fusion using a target-specific loop-mediated isothermal amplification method. TMPRSS2-ERG and androgen receptor RNA were detected down to 3x10 and 5x10 copies respectively in under 30 minutes.

Classification of nucleic acid amplification on ISFET arrays using spectrogram-based neural networks.

The COVID-19 pandemic has highlighted a significant research gap in the field of molecular diagnostics. This has brought forth the need for AI-based edge solutions that can provide quick diagnostic results whilst maintaining data privacy, security and high standards of sensitivity and specificity. This paper presents a novel proof-of-concept method to detect nucleic acid amplification using ISFET sensors and deep learning.

Detection of YAP1 and AR-V7 mRNA for Prostate Cancer Prognosis Using an ISFET Lab-On-Chip Platform.

Prostate cancer (PCa) is the second most common cause of male cancer-related death worldwide. The gold standard of treatment for advanced PCa is androgen deprivation therapy (ADT). However, eventual failure of ADT is common and leads to lethal metastatic castration-resistant PCa.

Low re-dislocation rate following Bereiter trochleoplasty for recurrent patellar instability with severe trochlear dysplasia.

Purpose: Trochlear dysplasia is an independent risk factor for recurrent patellar instability with evidence demonstrating its presence in up to 85% of patients with patellar instability. Severe trochlear dysplasia can be treated with trochleoplasty to improve engagement of the patella in the trochlear groove and prevent future dislocations. The aim of this study was to determine the clinical outcome of Bereiter trochleoplasty in patients with recurrent patellar instability and severe trochlear dysplasia.

Coronal-plane leg alignment in adolescence and the effects of activity: A full leg length MRI study.

The aim of this study was to explore the association between developing coronal-plane leg alignment and activity levels during adolescence. We performed a cross-sectional cohort study with individuals from soccer club academies and an age-matched control population. Outcome measures were the hip knee angle (HKA), medial proximal tibial physeal angle (MPTPhyA), lateral distal femoral physeal angle (LDFPhyA) on full leg length magnetic reasonance imagine scans, and the physical activity questionnaire (PAQ) score.

An Approach to a Patient With Primary Hyperparathyroidism and a Suspected Ectopic Parathyroid Adenoma.

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia driven by excess parathyroid hormone (PTH) secretion. PHPT is a common endocrine condition with a prevalence of 1 to 7 cases per 1000 adults. PHPT typically presents in the fifth or sixth decade and shows significant female preponderance.

Risk factors associated with poor pain outcomes following primary knee replacement surgery: Analysis of data from the clinical practice research datalink, hospital episode statistics and patient reported outcomes as part of the STAR research programme.

Objective: Identify risk factors for poor pain outcomes six months after primary knee replacement surgery.

Methods: Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale.

Life Expectancy in Duchenne Muscular Dystrophy: Reproduced Individual Patient Data Meta-analysis.

Background And Objectives: Duchenne muscular dystrophy (DMD) is a rare progressive disease that is often diagnosed in early childhood and leads to considerably reduced life expectancy; because of its rarity, research literature and patient numbers are limited. To fully characterize the natural history, it is crucial to obtain appropriate estimates of the life expectancy and mortality rates of patients with DMD.

Methods: A systematic review of the published literature on mortality in DMD up to July 2020 was undertaken, specifically focusing on publications in which Kaplan-Meier (KM) survival curves with age as a timescale were presented.

A longitudinal cohort study of adolescent elite footballers and controls investigating the development of cam morphology.

Cam morphology describes an asphericity of the femoral head that develops during adolescence, is highly prevalent in athletes, and predisposes individuals to future osteoarthritis. However, it's aetiology remains poorly understood. The aim of this study was to perform 3-year longitudinal follow-up of a control population and football club academy cohort to compare the change in hip and growth plate anatomy between athletes and controls.

Chemoenzymatic Cascades toward Methylated Tetrahydroprotoberberine and Protoberberine Alkaloids.

Tetrahydroprotoberberine and protoberberine alkaloids are a group of biologically active natural products with complex molecular scaffolds. Isolation from plants is challenging and stereoselective synthetic routes, particularly of methylated compounds are limited, reducing the potential use of these compounds. In this work, we describe chemoenzymatic cascades toward various 13-methyl-tetrahydroprotoberberbine scaffolds using a stereoselective Pictet-Spenglerase, regioselective catechol -methyltransferases and selective chemical Pictet-Spengler reactions.

Single step syntheses of (1S)-aryl-tetrahydroisoquinolines by norcoclaurine synthases.

The 1-aryl-tetrahydroisoquinoline (1-aryl-THIQ) moiety is found in many biologically active molecules. Single enantiomer chemical syntheses are challenging and although some biocatalytic routes have been reported, the substrate scope is limited to certain structural motifs. The enzyme norcoclaurine synthase (NCS), involved in plant alkaloid biosynthesis, has been shown to perform stereoselective Pictet-Spengler reactions between dopamine and several carbonyl substrates.

The Response of Hip Joint Cartilage to Exercise in Children: An MRI Study Using T2-Mapping.

Objective: The aim of this study was to determine the effects of activity and cam morphology on cartilage composition during adolescence and investigate the development of cartilage composition with age.

Design: Cross-sectional observational cohort study of individuals from football club academies and an age-matched control population, aged 9 to 18 years. Assessments included questionnaires and T2-mapping of hips.

No Evidence of Systemic Inflammation in Symptomatic Patients With Femoroacetabular Impingement.

Femoroacetabular impingement (FAI) is a common cause of hip pain and represents a major cause of early osteoarthritis. The role of systemic inflammation in pre-arthritic hip conditions remains largely unknown and uninvestigated. Serum-free light chains (sFLCs) are inflammatory markers produced by B cells.

Radiation dose mapping and anastomotic complications after trimodality therapy for esophageal cancers.

Background And Purpose: There is conflicting evidence with respect to the correlation between neoadjuvant chemoradiation and anastomotic complications following trimodality therapy in patients with esophageal cancer. We aimed to analyze the relationship between their dosimetry and any resulting anastomotic complications.

Materials And Methods: The medical records of 51 consecutive patients who underwent trimodality therapy between 2007 and 2014 were retrospectively reviewed.