Contemporary Non-Surgical Considerations in the Management of People with Extra- and Intra-Articular Hip Pathologies

The hip joint can often be affected by extra- and intra-articular pathologies including gluteal tendinopathy, femoroacetabular impingement syndrome and hip osteoarthritis. Understanding alterations associated with these pathologies will provide greater insight into developing and optimising patient-specific treatments. A number of biomechanical and neuromuscular impairment are associated with Femoracetabular impingement (FAI), gluteal tendinopathy (GT) and hip osteoarthritis (OA) conditions including but not limited to muscle weakness, altered postural control, restricted range of motion and altered tendon/joint loading. These alterations can present differently in sub-groups of patients and result directly from the pathological process and/or indirectly from pain and its consequences (e.g. reduced activity). These impairments are often targets for conservative interventions but there is currently little clinical trial evidence to show that treatments can modify these impairments. Clinical trial evidence does, however, support conservative treatment options for each of the pathologies reviewed. Clinical outcome tools used to evaluate the effects of treatment and track change over time are recommended

Effects of rehabilitative interventions on pain, function and physical impairments in people with hand osteoarthritis: a systematic review

INTRODUCTION: Hand osteoarthritis (OA) is associated with pain, reduced grip strength, loss of range of motion and joint stiffness leading to impaired hand function and difficulty with daily activities. The effectiveness of different rehabilitation interventions on specific treatment goals has not yet been fully explored. The objective of this systematic review is to provide evidence based knowledge on the treatment effects of different rehabilitation interventions for specific treatment goals for hand OA. METHODS: A computerized literature search of Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ISI Web of Science, the Physiotherapy Evidence Database (PEDro) and SCOPUS was performed. Studies that had an evidence level of 2b or higher and that compared a rehabilitation intervention with a control group and assessed at least one of the following outcome measures - pain, physical hand function or other measures of hand impairment - were included. The eligibility and methodological quality of trials were systematically assessed by two independent reviewers using the PEDro scale. Treatment effects were calculated using standardized mean difference and 95% confidence intervals. RESULTS: Ten studies, of which six were of higher quality (PEDro score >6), were included. The rehabilitation techniques reviewed included three studies on exercise, two studies each on laser and heat, and one study each on splints, massage and acupuncture. One higher quality trial showed a large positive effect of 12-month use of a night splint on hand pain, function, strength and range of motion. Exercise had no effect on hand pain or function although it may be able to improve hand strength. Low level laser therapy may be useful for improving range of motion. No rehabilitation interventions were found to improve stiffness. CONCLUSIONS: There is emerging high quality evidence to support that rehabilitation interventions can offer significant benefits to individuals with hand OA. A summary of the higher quality evidence is provided to assist with clinical decision making based on current evidence. Further high-quality research is needed concerning the effects of rehabilitation interventions on specific treatment goals for hand OA

Association of physical health multimorbidity with mortality in people with schizophrenia spectrum disorders: Using a novel semantic search system that captures physical diseases in electronic patient records

OBJECTIVE Single physical comorbidities have been associated with the premature mortality in people with schizophrenia-spectrum disorders (SSD). We investigated the association of physical multimorbidity (≥two physical health conditions) with mortality in people with SSD. METHODS A retrospective cohort study between 2013 and 2017. All people with a diagnosis of SSD (ICD-10: F20–F29), who had contact with secondary mental healthcare within South London during 2011–2012 were included. A novel semantic search system captured conditions from electronic mental health records, and all-cause mortality were retrieved. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated for associations between physical multimorbidity and all-cause mortality. RESULTS Among the 9775 people with SSD (mean (SD) age, 45.9 (15.4); males, 59.3%), 6262 (64%) had physical multimorbidity, and 880 (9%) died during the 5-year follow-up. The top three physical multimorbidity combinations with highest mortality were cardiovascular-respiratory (HR: 2.23; 95% CI, 1.49–3.32), respiratory-skin (HR: 2.06; 95% CI, 1.31–3.24), and respiratory-digestive (HR: 1.88; 95% CI, 1.14–3.11), when adjusted for age, gender, and all other physical disease systems. Combinations of physical diseases with highest PAFs were cardiovascular-respiratory (PAF: 35.7%), neurologic-respiratory (PAF: 32.7%), as well as respiratory-skin (PAF: 29.8%). CONCLUSIONS Approximately 2/3 of patients with SSD had physical multimorbidity and the risk of mortality in these patients was further increased compared to those with none or single physical conditions. These findings suggest that in order to reduce the physical health burden and subsequent mortality in people with SSD, proactive coordinated prevention and management efforts are required and should extend beyond the current focus on single physical comorbidities

Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting

OBJECTIVE: People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI. METHODS: An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries. RESULTS: Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019. CONCLUSION: Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population

Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as mechanisms of initiation may depend on the anatomical distribution of endometriotic lesions. However, amongst the numerous theories and plethora of mechanisms, contributions of the fallopian tubes (FT) to endometriosis are rarely discussed. The FT are implicated in all endometriosis associated symptomatology and clinical consequences; they may contribute to the origin of endometriotic tissue, determine the sites for ectopic lesion establishment and act as conduits for the spread of proinflammatory media. Here, we examine the available evidence for the contribution of the human FT to the origin, pathogenesis and symptoms/clinical consequences of endometriosis. We also examine the broader topic linking endometriosis and the FT epithelium to the genesis of ovarian epithelial cancers. Further studies elucidating the distinct functional and phenotypical characteristics of FT mucosa may allow the development of novel treatment strategies for endometriosis that are potentially curative

Developing Digital Tools for Remote Clinical Research:How to Evaluate the Validity and Practicality of Active Assessments in Field Settings

The ability of remote research tools to collect granular, high-frequency data on symptoms and digital biomarkers is an important strength because it circumvents many limitations of traditional clinical trials and improves the ability to capture clinically relevant data. This approach allows researchers to capture more robust baselines and derive novel phenotypes for improved precision in diagnosis and accuracy in outcomes. The process for developing these tools however is complex because data need to be collected at a frequency that is meaningful but not burdensome for the participant or patient. Furthermore, traditional techniques, which rely on fixed conditions to validate assessments, may be inappropriate for validating tools that are designed to capture data under flexible conditions. This paper discusses the process for determining whether a digital assessment is suitable for remote research and offers suggestions on how to validate these novel tools

Direct observations of amyloid β self-assembly in live cells provide insights into differences in the kinetics of Aβ(1-40) and Aβ(1-42) aggregation.

Insight into how amyloid β (Aβ) aggregation occurs in vivo is vital for understanding the molecular pathways that underlie Alzheimer's disease and requires new techniques that provide detailed kinetic and mechanistic information. Using noninvasive fluorescence lifetime recordings, we imaged the formation of Aβ(1-40) and Aβ(1-42) aggregates in live cells. For both peptides, the cellular uptake via endocytosis is rapid and spontaneous. They are then retained in lysosomes, where their accumulation leads to aggregation. The kinetics of Aβ(1-42) aggregation are considerably faster than those of Aβ(1-40) and, unlike those of the latter peptide, show no detectable lag phase. We used superresolution fluorescence imaging to examine the resulting aggregates and could observe compact amyloid structures, likely because of spatial confinement within cellular compartments. Taken together, these findings provide clues as to how Aβ aggregation may occur within neurons

Characterisation of Non-Autoinducing Tropodithietic Acid (TDA) Production from Marine Sponge Pseudovibrio Species.

The search for new antimicrobial compounds has gained added momentum in recent years, paralleled by the exponential rise in resistance to most known classes of current antibiotics. While modifications of existing drugs have brought some limited clinical success, there remains a critical need for new classes of antimicrobial compound to which key clinical pathogens will be naive. This has provided the context and impetus to marine biodiscovery programmes that seek to isolate and characterize new activities from the aquatic ecosystem. One new antibiotic to emerge from these initiatives is the antibacterial compound tropodithietic acid (TDA). The aim of this study was to provide insight into the bioactivity of and the factors governing the production of TDA in marine Pseudovibrio isolates from a collection of marine sponges. The TDA produced by these Pseudovibrio isolates exhibited potent antimicrobial activity against a broad spectrum of clinical pathogens, while TDA tolerance was frequent in non-TDA producing marine isolates. Comparative genomics analysis suggested a high degree of conservation among the tda biosynthetic clusters while expression studies revealed coordinated regulation of TDA synthesis upon transition from log to stationary phase growth, which was not induced by TDA itself or by the presence of the C10-acyl homoserine lactone quorum sensing signal molecule

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial)

Purpose To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. Materials and Methods In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29–85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. Results Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50–59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). Conclusion The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. © RSNA, 2015The TOMMY Trial (a comparison of digital breast tomosynthesis with mammography in the UK Breast Screening Programme) was supported by the NIHR Health Technology Assessment Programme.This is the final published version of the article. It was originally published in Radiology (Gilbert et al., Radiology, 2015, doi:10.1148/radiol.2015142566). The final version is available at http://dx.doi.org/10.1148/radiol.201514256

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).

PURPOSE: To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. MATERIALS AND METHODS: In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. RESULTS: Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). CONCLUSION: The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.The TOMMY Trial (a comparison of digital breast tomosynthesis with mammography in the UK Breast Screening Programme) was supported by the NIHR Health Technology Assessment Programme.This is the final published version of the article. It was originally published in Radiology (Gilbert et al., Radiology, 2015, doi:10.1148/radiol.2015142566). The final version is available at http://dx.doi.org/10.1148/radiol.201514256