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Female-Specific Factors in Chronic Neck and Back Pain: A Scoping Review of Clinical Practice Guidelines and Clinical Guidance Documents
No full textIntroduction
Females are disproportionally affected by chronic neck and back pain, but whether Clinical Practice Guidelines (CPGs) and Clinical Guidance Documents (CGDs) consider female-specific factors is unknown. This study aimed to identify the CPGs and CGDs that address female-specific factors in chronic neck and back pain, pinpointing any gaps that need addressing to optimise female-specific healthcare.
Methods
A scoping review was conducted following Arksey and O’Malley’s methodological framework and PRISMA diagram, searching three electronic databases and five grey literature registries. Content, documentary and thematic analyses were performed.
Results
None of the nine included records mentioned ‘female’ or ‘sex,’ four mentioned ‘woman’/‘women,’ and one mentioned ‘gender.’ Three themes emerged: use of sex-related epidemiological context in guideline framing; patient-centred but not sex-considered approaches to healthcare; women’s health and reproductive health considerations.
Discussion
While patient-centred approaches to pain management are encouraged, sex-specific factors remain overlooked when managing general health conditions, risking suboptimal care and outcomes
Do lifestyle factors affect clinical outcomes following total knee replacement? An integrated qualitative study exploring the perceptions and experiences of participants in the PRO Knee feasibility cohort study
No full textBackground
The development of pre-operative interventions to improve clinical outcomes following total knee replacement surgery has been identified as a research priority. In the first step of a programme of research, we conducted a feasibility cohort study, which investigated the effect of modifiable lifestyle factors, including alcohol consumption, smoking, physical inactivity and living with overweight, on clinical outcomes following total knee replacement (PRO Knee). Alongside PRO Knee, we conducted an integrated qualitative study to understand the acceptability of the methods used in the PRO Knee study and to explore the experiences of patients waiting for total knee replacement surgery, along with their beliefs and experiences regarding lifestyle interventions.
Methods
Adult patients awaiting total knee replacement surgery, who had consented to participate in the PRO Knee study were eligible to participate. Semi structured interviews were conducted with all patients who provided informed consent for the qualitative study. Interviews were audio-recorded; transcribed in an intelligent verbatim format and data were analysed using the Framework Method.
Results
Ten participants (9 female, 1 male) were recruited (average age 70, range 56–88) and all interviews were conducted over the telephone. The recruitment and data collection processes of the PRO Knee study were acceptable to participants. Five further themes relating to the lived experience of waiting for and undergoing total knee replacement surgery were identified: 1) Osteoarthritis of the knee and co-morbidity; 2) The decision to have surgery; 3) Waiting for total knee replacement; 4) Lifestyle conversations and interventions; 5) Recovery from total knee replacement.
The burden of living with osteoarthritis of the knee was significant and participants had often experienced multiple unsuccessful interventions. Participants could recall lifestyle conversations, which they were open to, but were not offered support. Most participants were positive about participating in lifestyle interventions prior to surgery. The participants who had poor outcomes were left with intrusive pain, and feelings of regret.
Conclusion
The recruitment and data collection processes for the PRO-Knee feasibility cohort study were acceptable to participants and further study in this area is now warranted
Probing the Universe: A Geometrical View for Observers of Spacetime Physics
No full textThis book provides a fresh perspective on the relationships between gravitation, electrodynamics, and quantum physics. Designed for graduate students and postdoctoral researchers with a background in mathematical physics, it organizes key ideas into a series of paradigms inspired by the history of scientific discoveries, from Aristotle and Euclid to modern physics. Framed within the language of modern differential geometry, these paradigms rely on essential concepts such as fiber bundles and manifolds, which are introduced in the text. Although the primary focus is on Einstein’s theory of gravitation, the discussion is set within a broader mathematical framework that includes arbitrary dimensional manifolds with linear connections, metric tensor fields (with any signature), torsion, and metric gradients. A chapter introduces the concept of Frenet-Serret frames along curves in various arbitrary-dimensional manifolds with metric tensor fields of arbitrary signature and provides examples relevant to spacetime physics. The book makes precise the concept of an “ideal spacetime observer” and a “standard clock in spacetime”, highlighting the inevitable role of quantum wave-particle duality in interpreting local measurement processes.
The text offers a variational approach to deriving generalized theories of gravitation interacting with matter using the exterior calculus of differential forms. This provides an efficient calculus for deriving stress-energy-momentum tensors and leads to a detailed analysis of the Einstein-Maxwell paradigm in spacetime. Killing vector and Killing tensor fields are employed in analyzing the geodesics of Schwarzschild, Reissner-Nordstrom and Kerr spacetimes. Throughout the book emphasis is placed upon distinguishing between geometric and co-ordinate singularities, and is illustrated using charts constructed by Painleve-Gullstrand and Kruskal-Szekeres, leading to a discussion of the properties of black hole spacetimes. A geometrical framework is provided for analyzing the Tolman-Oppenheimer-Volkoff theory for stellar interiors and a chapter examines the “Oppenheimer-Schiff Debate” about the electromagnetic fields generated by rotating charged shells, clarifying key points in the literature. A chapter introduces chiral pulse models in Maxwell electrodynamics, Bopp-Lande-Podolsky electrodynamics and linearised Einstein gravitation. Spinor fields are introduced as sections of a Clifford algebra bundle and used to discuss spinor pulse fields in Minkowski spacetime. Several appendices complement the main text. They include a guide to notations, detailed proofs of mathematical identities, a table of physical dimensions for quantities discussed, and a primer on set and measure theory. For readers interested in further exploration, additional appendices outline the mathematical foundations of quantum mechanics, providing a stepping stone to future paradigms in modern physics
The Gut Microbiome at the Onset of Inflammatory Bowel Disease: A Systematic Review and Unified Bioinformatic Synthesis
No full textBackground & Aims
Few studies describe gut microbiome signatures in treatment-naïve new-onset inflammatory bowel disease (IBD). We present a novel secondary bioinformatic reanalysis of sequence outputs mapped to the latest microbial taxonomy.
Methods
MEDLINE and Embase searches were performed for microbiome studies in treatment-naïve IBD. Appraisal was completed with Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Available 16S ribosomal RNA sequence data sets were downloaded and missing data sets requested. Integrated data were run through a unified QIIME2 bioinformatics pipeline. Multivariable models adjusting for methodologic differences were developed using MaAsLin2.
Results
There were 36 eligible studies; 18 contributed to bioinformatic reanalysis and 24 to supplementary meta-analysis. Samples from 1743 patients were included, comprising 678 from individuals with Crohn’s disease (CD), 399 with ulcerative colitis (UC), 130 healthy controls (HCs), and 405 symptomatic controls (SCs); 990 of which were biopsy samples. Alpha diversity was reduced: feces-pediatric UC vs SCs, adult CD and UC vs HCs, and pediatric SCs vs HCs; pediatric biopsy samples-CD vs SCs, CD vs UC, and UC vs SCs. Beta diversity demonstrated clear distinctions between fecal and mucosal biopsy communities, least evident in UC, in addition to community separation by geography. Multivariate modeling revealed depletion of anaerobic and enrichment of aerobic and facultative anaerobic bacteria, alongside enrichment of oral genera across both CD and UC.
Conclusions
Core microbial perturbations at onset of CD and UC are depletion of anaerobes and enrichment of oxygen-tolerant, orally associated bacteria. As we place greater emphasis on early diagnosis and prediction of IBD risk, this finding may support innovative diagnostic approaches. Microbiome-targeted intervention and alteration of luminal oxygen availability may offer novel therapeutic avenues for new-onset patients and identified high-risk groups
Effects of Prior Local Therapy by Radical Prostatectomy or Radiotherapy on the Efficacy and Quality of Life of Patients Treated With Darolutamide in ARAMIS
No full textBackground: Darolutamide plus androgen‐deprivation therapy (ADT) improved metastasis‐free survival (MFS) by 2 years and reduced the risk of death by 31% in nonmetastatic castration‐resistant prostate cancer (nmCRPC) in ARAMIS. Prior local therapy may influence the efficacy of subsequent systemic therapy. This post hoc analysis of ARAMIS evaluated the effect of prior local therapy on the efficacy and health‐related quality of life (HRQoL) of darolutamide. Methods: Patients with nmCRPC were randomized to darolutamide (n = 955) or placebo (n = 554) while continuing ADT. MFS, overall survival (OS), time to prostate‐specific antigen (PSA) progression, and HRQoL deterioration‐free survival (DetFS) were estimated for patients with and without local therapy and by treatment using Kaplan–Meier methods. Results: Darolutamide increased MFS versus placebo in patients with (HR, 0.36; 95% CI, 0.26–0.48) and without (HR, 0.46; 95% CI, 0.36–0.59) local therapy. Median OS was 48.6 months for placebo without local therapy and not reached in either the darolutamide group or placebo group with local therapy. Darolutamide 3‐year OS rates were 86.9% (95% CI, 83.0–90.8) and 79.0% (95% CI, 66.2–78.1) in patients with and without local therapy, respectively. Darolutamide showed evidence of improved OS versus placebo in patients with prior local therapy (HR, 0.80; 95% CI, 0.50–1.30) and a greater effect in those without local therapy (HR, 0.67; 95% CI, 0.50–0.90). Darolutamide delayed time to PSA progression and HRQoL deterioration regardless of local therapy. Conclusions: Darolutamide versus placebo improved MFS, OS, time to PSA progression, and HRQoL DetFS independent of prior local therapy, consistent with the overall ARAMIS population. Trial Registration: ClinicalTrials.gov registration: NCT0220061
A multi-omic liquid biopsy for the earlier detection of colorectal cancer
No full textTimely diagnosis and intervention in colorectal cancer (CRC) are critical to improving patient outcomes and limiting disease progression. Screening of average-risk individuals is essential for detecting tumors at an earlier, more treatable stage. However, adherence to current screening programs remains suboptimal. Liquid biopsies represent a promising alternative to stool-based tests and may play a key role in optimizing CRC detection and diagnostic pathways. In this study, 957 patients were recruited across various clinical sites in the USA: 48 CRC, 157 advanced precancerous lesions (APL), 331 non-advanced lesions (NAL) and 421 with a negative colonoscopy diagnosis. Blood was obtained from patients either prior to scheduled colonoscopy or before surgical resection and any anti-cancer therapies. Streck plasma samples were analyzed by the Dxcover® Liquid Biopsy Platform and classified with machine learning algorithms. When CRC was classified against all other groups, the receiver operating characteristic curve generated an area under the curve value of 0.95, and test sensitivity and specificity were 90% and 89%, respectively. The diagnostic model accurately predicted 75% of stage I (3/4), 100% of stage II (15/15), 93% of stage III (14/15) and 100% of stage IV (6/6) CRCs. For the advanced colorectal neoplasia model, 29% of APL were detected. A simple blood test with high sensitivity for early-stage colorectal cancer could significantly enhance patient outcomes. With continued development, this liquid biopsy has the potential to make a substantial impact on the early detection of CRC
Estimating real-world treatment effects in the presence of measurement error and sparse outcome data using propensity score methods
No full textIntroduction: The real-world treatment effect of a novel treatment can be estimated by analysing routinely collected patient data, in the form of Electronic Health Records (EHR). Any treatment allocation in EHR is not randomised and there may be systematic differences between the treatment groups. Propensity Score (PS) methods are commonly used to correct for these differences and reduce the bias in the treatment effect estimate. The aims of the study were to compare the performance of the most popular PS methods in the estimation of the treatment effect in the presence of two common issues in EHRs: covariate measurement error and sparse data.
Methods: The motivational example for this study was the assessment of the treatment effect of the novel oral anti-coagulant Rivaroxaban compared with the previous standard treatment Warfarin for the prevention of future stroke in patients with atrial fibrillation. Using simulation experiments based on a dataset comparing Rivaroxaban with Warfarin, we evaluated the performance of four PS methods.
Results: In the simulations with characteristics of the original dataset, using 3:1 PS matching generated a largest bias of +0.0428 (corresponding ratio of HRs (rHR) 1.0437), whereas for the other PS methods it was smaller and in negative direction: IPTW for ATE -0.0181 (rHR=0.9821); IPTW for ATT -0.0110 (rHR=0.9891); PS stratification -0.0099 (rHR=0.9901), with relative differences between rHRs being small to negligible. Fifty percent under-recording of a covariate (stroke) in the PS model, increased the MSE between 6%-11% compared to the MSE with no introduced measurement error. While 50% over-recording reduced the MSE by around 35%. The difference in the bias of the low prevalence outcome (0.5%) and the high prevalence outcome (10%) was: IPTW for ATE 0.1514 (rHRs=1.1635); IPTW for ATT 0.0160 (rHRs=1.0161); 3:1 PS matching 0.0758 (rHRs=1.0787); PS Stratification 0.0177 (rHRs=1.0179). A similar pattern for outcome prevalence was seen for all the simulation scenarios.
Conclusions: This study showed that PS methods proposed in the literature may not all perform well for individual datasets. The findings produced recommendations for using PS methods in the estimation of real-world treatment effect when the covariate measurement error and sparse outcome data are present
BlackTHUNDER strikes twice: Balmer-line absorption in an overmassive Little Red Dot at z = 7.04
No full textJWST has revealed a population of ‘Little Red Dots’ (LRDs): compact, red objects at redshifts z = 2–9 with ‘v’-shaped spectral energy distributions, broad permitted lines, and, often, hydrogen Balmer absorption. We use NIRSpec/IFS data from the BlackTHUNDER survey to study the H α line in the LRD Abell2744-QSO1 at z = 7.04, which is a confirmed AGN due to time-variable equivalent width (EW) in its broad emission lines. The H α spectral profile is non-Gaussian, requiring at least two Gaussian components. We also detect a narrow-line Gaussian component, and strong H α absorption (EW relative to the continuum ), confirming a connection between the strong Balmer break and line absorption. The absorber is at rest with respect to broad H α, suggesting that the gas cannot be interpreted as an inflow or outflow, forming instead a long-lived structure. Its velocity dispersion is km s−1, consistent with the value inferred from the analysis of the Balmer break. Based on H α, we infer a black hole mass of log (M•/M⊙) = 7.2, smaller but close to the previous estimates based on H β. The Eddington ratio is 0.09. Combining the high signal-to-noise ratio of the narrow H α line with the spectral resolution R = 3, 700 of the G395H grating, we infer a narrow-line intrinsic dispersion km s−1, which places a stringent constraint on the black-hole-to-dynamical-mass ratio of this system to be M•/Mdyn = 0.15–1.2, confirming the overmassive nature of the black hole and potentially leaving little room for a host galaxy
Three-Dimensional Burrowing Behavior of Earthworms for Ecotoxicological Studies
No full textEarthworm behavioral biomarkers provide more sensitive and comprehensive assessments for environmental contaminants. However, natural soil opaqueness has limited understanding of the continuous three-dimensional (3D) characteristics of earthworm burrowing activity. In this study, we developed an integrative method combining a transparent medium with a deep learning-based trajectory reconstruction algorithm to quantitatively investigate species-specific burrowing strategies. Earthworms thrived in the transparent medium, as shown by biomass increase (0.62 to 0.72 g) and >80% survival over the 28-day trial, while algorithm operational stability (83.65% coordinate extraction rate) allowed continuous tracking of the earthworm spatial coordinates in 3D locations. Comparative analysis across five earthworm species revealed species-specific patterns: Eisenia fetida, Amynthas pectiniferus, and Eudrilus eugeniae preferred surface layers and moved laterally, whereas Perionyx excavatus and Metaphire guillelmi created vertical burrows. These findings are valuable for quantifying soil health assessments using different earthworm species. Moreover, this method successfully captured avoidance behavior in arsenate-contaminated soils, as arsenic exposure inhibited cumulative burrowing length. These results establish a critical tool for advancing ecological risk assessment and management of soil pollutants by offering visual and quantitative insights into 3D earthworm burrowing dynamics, and provide potential applications in ecology, environmental pollution monitoring, and remediation
Islands in infinity
No full textThrough their three-dimensional vision of the cosmos, Brian May, Derek Ward-Thompson and J-P Metsävainio invite us to reimagine both space and our place in it