Multisite pain and self-reported falls in older people: systematic review and meta-analysis.

BACKGROUND: Multisite pain and falls are common in older people, and isolated studies have identified multisite pain as a potential falls risk factor. This study aims to synthesise published literature to further explore the relationship between multisite pain and falls and to quantify associated risks. METHODS: Bibliographic databases were searched from inception to December 2017. Studies of community-dwelling adults aged 50 years and older with a multisite pain measurement and a falls outcome were included. Two reviewers screened articles, undertook quality assessment and extracted data. Random-effects meta-analysis was used to pool the effect estimate (odds ratio (OR) and 95% confidence interval (95%CI)). Heterogeneity was assessed by I2; sensitivity analyses used adjusted risk estimates and exclusively longitudinal studies. RESULTS: The search identified 49,577 articles, 3145 underwent abstract review, 22 articles were included in the systematic review and 18 were included in the meta-analysis. The unadjusted pooled OR of 1.82 (95%CI 1.55-2.13), demonstrating that those reporting multisite pain are at increased risk of falls, is supported by the adjusted pooled OR of 1.56 (95%CI 1.39-1.74). Multisite pain predicts future falls risk (OR = 1.74 (95%CI 1.57-1.93)). For high-quality studies, those reporting multisite pain have double the odds of a future fall compared to their pain-free counterparts. CONCLUSION: Multisite pain is associated with an increased future falls risk in community-dwelling older people. Increasing public awareness of multisite pain as a falls risk factor and advising health and social care professionals to identify older people with multisite pain to signpost accordingly will enable timely falls prevention strategies to be implemented

Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction.

OBJECTIVES: Despite many shared risk factors and pathophysiological pathways, the risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in interstitial lung disease (ILD) remains poorly understood. This lack of data could be preventing patients who may benefit from screening for these cardiovascular diseases from receiving it. METHODS: A population-based cohort study used electronic patient records from the Clinical Practice Research Datalink and linked Hospital Episode Statistics to identify 68 572 patients (11 688 ILD exposed (mean follow-up: 3.8 years); 56 884 unexposed controls (mean follow-up: 4.0 years), with 349 067 person-years of follow-up. ILD-exposed patients (pulmonary sarcoidosis (PS) or idiopathic pulmonary fibrosis (PF)) were matched (by age, sex, registered general practice and available follow-up time) to patients without ILD or IHD/MI. Rates of incident MI and IHD were estimated. HRs were modelled using multivariable Cox proportional hazards regression accounting for potential confounders. RESULTS: ILD was independently associated with IHD (HR 1.85, 95% CI 1.56 to 2.18) and MI (HR 1.74, 95% CI 1.44 to 2.11). In all disease categories, risk of both IHD and MI peaked between ages 60 and 69 years, except for the risk of MI in PS which was greatest <50 years. Men with PF were at greatest risk of IHD, while women with PF were at greatest risk of MI. CONCLUSIONS: ILD, particularly PF, is independently associated with MI and IHD after adjustment for established cardiovascular risk factors. Our results suggest clinicians should prioritise targeted assessment of cardiovascular risk in patients with ILD, particularly those aged 60-69 years. Further research is needed to understand the impact of such an approach to risk management

Completion of fit notes by GPs: a mixed methods study

Aims: The aim of this study was to investigate the completion of fit notes by UK general practitioners (GPs). A series of actual fit notes issued to employed patients were examined, and their GPs’ reflections and experiences of fit note completion explored. Methods: A mixed-methods design was used. Data were collected from copies of 94 fit notes issued to employed patients by 11 GPs, and from 86 questionnaires completed by these GPs reflecting on the fit notes they had issued. Face-to-face interviews were then conducted with each GP. Results: Fit note completion is not meeting expectations for a number of reasons. These include the following: limited knowledge and awareness of the guidance in fit note completion; problems with the fit note format; lack of mandatory training in completing fit notes; lack of incentive to change practice; incomplete implementation of the electronic fit note; GPs’ lack of confidence in, and doubts about the appropriateness of performing this role. Conclusion: If UK GPs are to continue their contractual responsibility for completing fit notes, further consideration of their education and training needs is urgently required. Weaknesses in the design and format of the fit note and the availability of the electronic version also need to be addressed

The impact of the COVID-19 pandemic on referrals to musculoskeletal services from primary care and subsequent incidence of inflammatory rheumatic musculoskeletal disease: an observational study

Objectives To describe the impact of the COVID-19 pandemic upon referral patterns and incident diagnosis of inflammatory rheumatic and musculoskeletal diseases (iRMDs). Methods UK primary care data was used to describe referral patterns for patients with musculoskeletal conditions. Trends in referrals to musculoskeletal services and incident diagnoses of iRMDs (specifically rheumatoid arthritis (RA) and juvenile inflammatory arthritis (JIA)) were described using Joinpoint Regression and comparisons made between key pandemic time periods. Results The incidence of RA and JIA reduced by -13.3% and -17.4% per month respectively between January 2020 and April 2020, and then increased by 1.9% and 3.7% per month respectively between April 2020 and October 2021. The incidence of all diagnosed iRMDs was stable until October 2021. Referrals decreased between February 2020 and May 2020 by -16.8% per month from 4.8% to 2.4% in patients presenting with a musculoskeletal condition. After May 2020, referrals increased significantly (16.8% per month) to 4.5% in July 2020. Time from first musculoskeletal consultation to RA diagnosis, and referral to RA diagnosis increased in the early-pandemic period (rate ratio (RR) 1.11, 95%CI 1.07-1.15; RR 1.23, 95%CI 1.17-1.30) and remained consistently higher in the late-pandemic (RR 1.13, 95%CI 1.11-1.16; RR 1.27, 95%CI 1.23-1.32) periods respectively, compared to the pre-COVID-19 period. Conclusion Patients with underlying RA and JIA that developed during the pandemic may be yet to present, or be in the referral and/or diagnostic process. Clinicians should remain alert to this possibility and commissioners aware of these findings, enabling the appropriate planning and commissioning of services

The EBLM project-VII. Spin-orbit alignment for the circumbinary planet host EBLM J0608-59 A/TOI-1338 A

A dozen short-period detached binaries are known to host transiting circumbinary planets. In all circumbinary systems so far, the planetary and binary orbits are aligned within a couple of degrees. However, the obliquity of the primary star, which is an important tracer of their formation, evolution, and tidal history, has only been measured in one circumbinary system until now. EBLM J0608-59/TOI-1338 is a low-mass eclipsing binary system with a recently discovered circumbinary planet identified by TESS. Here, we perform high-resolution spectroscopy during primary eclipse to measure the projected stellar obliquity of the primary component. The obliquity is low, and thus the primary star is aligned with the binary and planetary orbits with a projected spin-orbit angle $\beta = 2.8 \pm 17.1$ deg. The rotation period of $18.1 \pm 1.6$ days implied by our measurement of $v\sin{i_\star}$ suggests that the primary has not yet pseudo-synchronized with the binary orbit, but is consistent with gyrochronology and weak tidal interaction with the binary companion. Our result, combined with the known coplanarity of the binary and planet orbits, is suggestive of formation from a single disc. Finally, we considered whether the spectrum of the faint secondary star could affect our measurements. We show through simulations that the effect is negligible for our system, but can lead to strong biases in $v\sin{i_\star}$ and $\beta$ for higher flux ratios. We encourage future studies in eclipse spectroscopy test the assumption of a dark secondary for flux ratios $\gtrsim 1$ ppt

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Quantification of Circadian Rhythms in Single Cells

Bioluminescence techniques allow accurate monitoring of the circadian clock in single cells. We have analyzed bioluminescence data of Per gene expression in mouse SCN neurons and fibroblasts. From these data, we extracted parameters such as damping rate and noise intensity using two simple mathematical models, one describing a damped oscillator driven by noise, and one describing a self-sustained noisy oscillator. Both models describe the data well and enabled us to quantitatively characterize both wild-type cells and several mutants. It has been suggested that the circadian clock is self-sustained at the single cell level, but we conclude that present data are not sufficient to determine whether the circadian clock of single SCN neurons and fibroblasts is a damped or a self-sustained oscillator. We show how to settle this question, however, by testing the models' predictions of different phases and amplitudes in response to a periodic entrainment signal (zeitgeber)

Recommendations to facilitate the ideal fit note: are they achievable in practice?

Background: Although the UK fit note has been broadly welcomed as a tool to facilitate return to work, difficulties and uncertainties have resulted in wide variation in its use. Agreement on what constitutes the ‘ideal’ fit note from the perspective of all stakeholders is needed to inform best practice. A recent Delphi study conducted by the authors reached consensus on 67 recommendations for best practice in fit note use for employed patients. However, such recommendations are not necessarily followed in practice. The purpose of this study was therefore to investigate the perceived achievability of implementing these Delphi recommendations with a further reference panel of stakeholders. Methods: Potential participants were identified by the research team and study steering group. These included representatives of employers, government departments, trades unions, patient organisations, general and medical practitioners and occupational health organisations who were believed to have the knowledge and experience to comment on the recommendations. The consensus Delphi statements were presented to the participants on-line. Participants were invited to comment on whether the recommendations were achievable, and what might hinder or facilitate their use in practice. Free text comments were combined with comments made in the Delphi study that referred to issues of feasibility or practicality. These were synthesised and analysed thematically. Results: Twelve individuals representing a range of stakeholder groups participated. Many of the recommendations were considered achievable, such as improved format and use of the electronic fit note, completion of all fields, better application and revision of guidance and education in fit note use. However a number of obstacles to implementation were identified. These included: legislation governing the fit note and GP contracts; the costs and complexity of IT systems and software; the limitations of the GP consultation; unclear roles and responsibilities for the funding and delivery of education, guidance and training for all stakeholders, and the evaluation of practice. Conclusions: This study demonstrated that although many recommendations for the ideal fit note are considered achievable, there are considerable financial, legal, organisational and professional obstacles to be overcome in order for the recommendations to be implemented successfully

SLEPR: A Sample-Level Enrichment-Based Pathway Ranking Method — Seeking Biological Themes through Pathway-Level Consistency

Analysis of microarray and other high throughput data often involves identification of genes consistently up or down-regulated across samples as the first step in extraction of biological meaning. This gene-level paradigm can be limited as a result of valid sample fluctuations and biological complexities. In this report, we describe a novel method, SLEPR, which eliminates this limitation by relying on pathway-level consistencies. Our method first selects the sample-level differentiated genes from each individual sample, capturing genes missed by other analysis methods, ascertains the enrichment levels of associated pathways from each of those lists, and then ranks annotated pathways based on the consistency of enrichment levels of individual samples from both sample classes. As a proof of concept, we have used this method to analyze three public microarray datasets with a direct comparison with the GSEA method, one of the most popular pathway-level analysis methods in the field. We found that our method was able to reproduce the earlier observations with significant improvements in depth of coverage for validated or expected biological themes, but also produced additional insights that make biological sense. This new method extends existing analyses approaches and facilitates integration of different types of HTP data