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

P181 Musculoskeletal pain and prognosis of acute coronary syndrome and cerebrovascular accident: a linked electronic health record cohort study

Abstract Background/Aims There is some evidence of an increased risk of cardiovascular disease in patients with painful musculoskeletal conditions, but it is unclear if musculoskeletal pain also worsens its prognosis. The aim was to determine whether patients with musculoskeletal pain have poorer prognosis following acute coronary syndrome (ACS) or cerebrovascular accident (CVA). Methods Data were obtained from national primary care electronic health records (Clinical Practice Research Datalink; CPRD) with linkage to hospital admissions and mortality records. Patients aged 45 years and over with ACS or CVA recorded in primary care and as the primary reason for hospital admission within ±30 days were included. Patients were grouped by consultations in primary care for painful musculoskeletal conditions (by recency/severity and by condition) in the 24 months prior to ACS or CVA. Severe musculoskeletal pain was defined as prescription of strong analgesia or relevant secondary care referral in the 6 months before ACS or CVA. Short-term outcomes included length of hospital stay, mortality during admission or within 30 days of discharge, and readmission within 30 days of discharge. Management outcomes included procedures during admission and prescriptions for anti-hypertensives, anti-platelets and anti-coagulants in the 3 months following admission. Longer term outcomes included further ACS or CVA and mortality in those who survived &amp;gt;30 days after discharge. Results There were 171,670 patients with ACS (36% females; median age 70 years) and 138,512 patients with CVA (49% females; median age 76 years); 30% of patients in each cohort consulted for a painful musculoskeletal condition prior to admission for ACS or CVA. An increased prevalence of cardiovascular risk factors was observed for patients with severe musculoskeletal pain compared to those without pain for comorbidities such as obesity (ACS 26% vs 16%, CVA 25% vs 15%), diabetes (ACS 24% vs 17%, CVA 23% vs 17%) and lifestyle characteristics such as current/ex-smoker (ACS 58% vs 52%, CVA 52% vs 46%), respectively. Patients with severe musculoskeletal pain had similar lengths of stay, rates of readmission and further ACS/CVA after adjustment for sociodemographic characteristics and comorbidities than those without musculoskeletal pain. They were more likely to receive a procedure during admission for ACS (adjusted risk ratio [aRR] 1.15, 95% confidence interval [CI] 1.03-1.28). Prescriptions for ACS (severe pain aRR 1.01, 95% CI 1.00-1.02; inflammatory condition aRR 1.01, 95% CI 1.00-1.02) and CVA (inflammatory condition aRR 1.04, 95% CI 1.01-1.06) were higher in the 3 months post-admission for those with musculoskeletal pain. Conclusion Musculoskeletal pain did not independently worsen the prognosis following hospitalisation for incident ACS or CVA. The findings are reassuring, but also highlight the need for closer surveillance due to the complexities of patients with severe musculoskeletal presenting with incident ACS or CVA. Disclosure K.J. Mason: None. K.P. Jordan: None. F.A. Achana: None. J. Bailey: None. Y. Chen: None. M. Frisher: None. A.L. Huntley: None. C.D. Mallen: None. M.A. Mamas: None. M. Png: None. S. Tatton: None. S. White: None. J.J. Edwards: None. </jats:sec

Brief pain re-assessment provided more accurate prognosis than baseline information for low-back or shoulder pain

Background Research investigating prognosis in musculoskeletal pain conditions has only been moderately successful in predicting which patients are unlikely to recover. Clinical decision making could potentially be improved by combining information taken at baseline and re-consultation. Methods Data from four prospective clinical cohorts of adults presenting to UK and Dutch primary care with low-back or shoulder pain was analysed, assessing long-term disability at 6 or 12 months and including baseline and 4–6 week assessments of pain. Baseline versus short-term assessments of pain, and previously validated multivariable prediction models versus repeat assessment, were compared to assess predictive performance of long-term disability outcome. A hypothetical clinical scenario was explored which made efficient use of both baseline and repeated assessment to identify patients likely to have a poor prognosis and decide on further treatment. Results Short-term repeat assessment of pain was better than short-term change or baseline score at predicting long-term disability improvement across all cohorts. Short-term repeat assessment of pain was only slightly more predictive of long-term recovery (c-statistics 0.78, 95% CI 0.74 to 0.83 and 0.75, 95% CI 0.69 to 0.82) than a multivariable baseline prognostic model in the two cohorts presenting such a model (c-statistics 0.71, 95% CI 0.67 to 0.76 and 0.72, 95% CI 0.66 to 0.78). Combining optimal prediction at baseline using a multivariable prognostic model with short-term repeat assessment of pain in those with uncertain prognosis in a hypothetical clinical scenario resulted in reduction in the number of patients with an uncertain probability of recovery, thereby reducing the instances where patients may be inappropriately referred or reassured. Conclusions Incorporating short-term repeat assessment of pain into prognostic models could potentially optimise the clinical usefulness of prognostic information

Polar vortex formation in giant-planet atmospheres due to moist convection

A strong cyclonic vortex has been observed on each of Saturn’s poles, coincident with a local maximum in observed tropospheric temperature. Neptune also exhibits a relatively warm, although much more transient, region on its south pole. Whether similar features exist on Jupiter will be resolved by the 2016 Juno mission. Energetic, small-scale storm-like features that originate from the water-cloud level or lower have been observed on each of the giant planets and attributed to moist convection, suggesting that these storms play a significant role in global heat transfer from the hot interior to space. Nevertheless, the creation and maintenance of Saturn’s polar vortices, and their presence or absence on the other giant planets, are not understood. Here we use simulations with a shallow-water model to show that storm generation, driven by moist convection, can create a strong polar cyclone throughout the depth of a planet’s troposphere. We find that the type of shallow polar flow that occurs on a giant planet can be described by the size ratio of small eddies to the planetary radius and the energy density of its atmosphere due to latent heating from moist convection. We suggest that the observed difference in these parameters between Saturn and Jupiter may preclude a Jovian polar cyclone.National Science Foundation (U.S.). Graduate Research FellowshipNational Science Foundation (U.S.) (ATM-0850639)National Science Foundation (U.S.) (AGS-1032244)National Science Foundation (U.S.) (AGS-1136480)United States. Office of Naval Research (N00014-14-1-0062

3-Deazaneplanocin A (DZNep), an Inhibitor of the Histone Methyltransferase EZH2, Induces Apoptosis and Reduces Cell Migration in Chondrosarcoma Cells

ObjectiveGrowing evidences indicate that the histone methyltransferase EZH2 (enhancer of zeste homolog 2) may be an appropriate therapeutic target in some tumors. Indeed, a high expression of EZH2 is correlated with poor prognosis and metastasis in many cancers. In addition, 3-Deazaneplanocin A (DZNep), an S-adenosyl-L homocysteine hydrolase inhibitor which induces EZH2 protein depletion, leads to cell death in several cancers and tumors. The aim of this study was to determine whether an epigenetic therapy targeting EZH2 with DZNep may be also efficient to treat chondrosarcomas.MethodsEZH2 expression was determined by immunohistochemistry and western-blot. Chondrosarcoma cell line CH2879 was cultured in the presence of DZNep, and its growth and survival were evaluated by counting adherent cells periodically. Apoptosis was assayed by cell cycle analysis, Apo2.7 expression using flow cytometry, and by PARP cleavage using western-blot. Cell migration was assessed by wound healing assay.ResultsChondrosarcomas (at least with high grade) highly express EZH2, at contrary to enchondromas or chondrocytes. In vitro, DZNep inhibits EZH2 protein expression, and subsequently reduces the trimethylation of lysine 27 on histone H3 (H3K27me3). Interestingly, DZNep induces cell death of chondrosarcoma cell lines by apoptosis, while it slightly reduces growth of normal chondrocytes. In addition, DZNep reduces cell migration.ConclusionThese results indicate that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treat chondrosarcomas

Ocular accommodation and cognitive demand: An additional indicator besides pupil size and cardiovascular measures?

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to assess accommodation as a possible indicator of changes in the autonomic balance caused by altered cognitive demand. Accounting for accommodative responses from a human factors perspective may be motivated by the interest of designing virtual image displays or by establishing an autonomic indicator that allows for remote measurement at the human eye. Heart period, pulse transit time, and the pupillary response were considered as reference for possible closed-loop accommodative effects. Cognitive demand was varied by presenting monocularly numbers at a viewing distance of 5 D (20 cm) which had to be read, added or multiplied; further, letters were presented in a "n-back" task.</p> <p>Results</p> <p>Cardiovascular parameters and pupil size indicated a change in autonomic balance, while error rates and reaction time confirmed the increased cognitive demand during task processing. An observed decrease in accommodation could not be attributed to the cognitive demand itself for two reasons: (1) the cognitive demand induced a shift in gaze direction which, for methodological reasons, accounted for a substantial part of the observed accommodative changes. (2) Remaining effects disappeared when the correctness of task processing was taken into account.</p> <p>Conclusion</p> <p>Although the expectation of accommodation as possible autonomic indicator of cognitive demand was not confirmed, the present results are informative for the field of applied psychophysiology noting that it seems not to be worthwhile to include closed-loop accommodation in future studies. From a human factors perspective, expected changes of accommodation due to cognitive demand are of minor importance for design specifications – of, for example, complex visual displays.</p

Musculoskeletal pain and its impact on prognosis following acute coronary syndrome or stroke: A linked electronic health record cohort study.

OBJECTIVE: Musculoskeletal painful conditions are a risk factor for cardiovascular disease (CVD), but less is known about whether musculoskeletal pain also worsens prognosis from CVD. The objective was to determine whether patients with musculoskeletal pain have poorer prognosis following acute coronary syndrome (ACS) or stroke. METHODS: The study utilised UK electronic primary care records (CPRD Aurum) with linkage to hospital and mortality records. Patients aged ≥45 years admitted to hospital with incident ACS/stroke were categorised by healthcare use for musculoskeletal pain (inflammatory conditions, osteoarthritis [OA], and regional pain) based on primary care consultations in the prior 24 months. Outcomes included mortality, length of stay, readmission and management of index condition (ACS/stroke). RESULTS: There were 171,670 patients with incident ACS and 138,512 with stroke; 30% consulted for musculoskeletal pain prior to ACS/stroke and these patients had more comorbidity than those without musculoskeletal pain. Rates of mortality and readmission, and length of stay were higher in those with musculoskeletal pain, particularly OA and inflammatory conditions, in ACS. Readmission was also higher for patients with musculoskeletal pain in stroke. However, increased risks associated with musculoskeletal pain did not remain after adjustment for age and polypharmacy. Inflammatory conditions were associated with increased likelihood of prescriptions for dual anti-platelets (ACS only) and anti-coagulants. CONCLUSIONS: Patients with musculoskeletal pain have higher rates of poor outcome from ACS which relates to being older but also increased polypharmacy. The high rates of comorbidity including polypharmacy highlight the complexity of patients with musculoskeletal pain who have new onset ACS/stroke