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Learning to identify CNS drug action and efficacy using multistudy fMRI data
Existing functional brain imaging data sets were used to identify neural signatures that confirm pharmacological action and predict clinical efficacy of test compounds.
The natural history of chronic widespread pain in patients with axial spondyloarthritis: a cohort study with clinical and self-tracking data
Abstract Objectives This study investigates longitudinal patterns, predictors and long-term impact of pain in axial spondyloarthritis (axSpA), using clinical and self-tracking data. Methods The presence of multisite pain (MSP), affecting at least six of nine body regions using a Margolis pain drawing, and subsequent chronic widespread pain (CWP), MSP at more than one timepoint, was assessed in a cohort of axSpA patients. Incident MSP (MSP at two consecutive visits or more), intermittent MSP (MSP at two or more non-consecutive visits) and persistent MSP (MSP at each visit) were described. Demographic, clinical and self-tracking measures were compared for the CWP vs non-CWP groups using Students t test, Wilcoxon–Mann–Whitney and χ2 test for normal, non-normal and categorical data, respectively. Predictors of CWP were evaluated using logistic regression modelling. Results A total of 136 patients, mean clinical study duration of 120 weeks (range 27–277 weeks) were included, with sufficient self-tracking data in 97 patients. Sixty-eight (50%) patients reported MSP during at least one clinical visit: eight (6%) incident MSP; 16 (12%) persistent MSP; and 44 (32%) intermittent MSP. Forty-six (34%) of the cohort had CWP. All baseline measures of disease activity, function, quality of life, sleep disturbance, fatigue and overall activity impairment were significant predictors of the development of CWP. BASDAI and BASFI scores were significantly higher in those with CWP and self-tracking data revealed significantly worse pain, fatigue, sleep quality and stress. Conclusions The development of CWP is predicted by higher levels of disease activity and burden at baseline. It also impacts future disease activity and wellbeing.
Neuropathic Features of Joint Pain: A Community‐Based Study
ObjectiveQuantitative sensory testing (QST) and questionnaire‐based assessments have been used to demonstrate features of neuropathic pain in subjects with musculoskeletal pain. However, their direct relationship has not been investigated in the community. The purpose of this study was to conduct an observational study to describe the characteristics of joint pain and to examine the relationship between QST measures and the PainDETECT Questionnaire (PD‐Q).MethodsWarm detection, heat pain, and mechanical pain thresholds as well as mechanical pain sensitivity over the sternum were determined and the PD‐Q scores were calculated in a cross‐sectional study of 462 participants in the Chingford Study. Comparisons were made between subjects with and those without joint pain. Logistic regression modeling was used to describe the association between neuropathic pain features, as determined by the PD‐Q score, and each of the QST measures individually, adjusting for age, body mass index, and use of pain‐modifying medications.ResultsA total of 66.2% of the subjects reported recent joint pain, with a median average pain severity of 5 of 10. There was increased sensitivity to painful stimuli in the group with pain as compared to the pain‐free group, and this persisted after stratification by pain‐modifying medication use. While only 6.7% of subjects had possible neuropathic pain features and 1.9% likely neuropathic pain features according to the standard PD‐Q thresholds, features of neuropathic pain were common and were present in >50% of those reporting pain of at least moderate severity. Heat pain thresholds and mechanical pain sensitivity were significantly associated with features of neuropathic pain identified using the PD‐Q, with an odds ratio (OR) of 0.88 (95% confidence interval [95% CI] 0.79–0.97; P = 0.011) and an OR of 1.24 (95% CI 1.04–1.48; P = 0.018), respectively.ConclusionQST measures and the PD‐Q identified features of neuropathic pain in subjects in this community‐based study, with significant overlap between the findings of the two techniques.
Progression of chronic pain and associated health-related quality of life and healthcare resource use over 5 years after total knee replacement: evidence from a cohort study
ObjectiveAs part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery.MethodsWe used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data.ResultsChronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain.ConclusionAlthough TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems.
Sex-specific differences and how to handle them in early psoriatic arthritis
Abstract Objectives The prevalence of psoriatic arthritis (PsA) is the same in men and women; however, the latter experience a higher burden of disease and are affected more frequently by polyarthritis. Here, we performed an early PsA cohort analysis to assess sex-related differences in demographics, disease characteristics, and evolution over 1 year including applied treatment strategies. Methods Our study is embedded in the Dutch south-west Early Psoriatic Arthritis cohoRt. We described patient characteristics and treatment decisions. For the comparison across sexes and baseline and 1 year follow-up, appropriate tests depending on the distribution were used. Results Two hundred seventy-three men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly higher tender joint count, a higher disease activity, higher levels of pain, and lower functional capacity. Although minimal disease activity (MDA) rates increased over time for both sexes, MDA remained significantly more prevalent among men at 1 year (58.1% vs 35.7%, p < 0.00). Initially, treatment strategies were similar in both sexes with methotrexate being the most frequently used drug during the first year. Women received methotrexate for a shorter period [196 (93–364) vs 306 (157–365), p < 0.00] and therefore received a lower cumulative dose compared to men. Retention time was shorter for all DMARDs, and women had a delayed start on b-DMARDs. Conclusion After 1 year of standard-of-care treatment, women did not surpass their baseline disadvantages. Despite the overall improvement, they still presented higher disease activity, higher levels of pain, and lower functional capacity score than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in early PsA patients.
Neuropathic-like Pain in Fibrous Dysplasia/McCune-Albright Syndrome
Abstract Context Pain is a major symptom in adults with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) and response to current treatments, including bisphosphonates and standard analgesics (nonsteroidal anti-inflammatory drugs and opiates) is unpredictable. No studies have explored whether the type of pain is variable in this patient group. Objective To determine the frequency of neuropathic-like pain in patients with FD/MAS. Design Retrospective, dual registry study. Setting Community. Patients FD/MAS online registries: the US-based Familial Dysautonomia Foundation (FDF) and the UK-based Rare and Undiagnosed Diseases (RUDY) study. Intervention Subjects completed questionnaires to evaluate the presence of features of neuropathic-like pain (painDETECT) and the impact on sleep quality (Pittsburgh Sleep Quality Index) and mental health (Hospital Anxiety and Depression Scale). Descriptive statistics were used to characterize the prevalence and associated burden of neuropathic-like pain. Main Outcome Measures Incidence of neuropathic, nociceptive, and unclear pain. Results Of 249 participants, one third experienced neuropathic-like pain. This group had statistically significantly (P < 0.001) worse mental well-being and sleep in comparison to those with predominately nociceptive pain. Conclusions Neuropathic-like pain is common in patients with FD/MAS and associated with worse quality of life. Evaluation of pain in patients with FD/MAS should include assessment of neuropathic-like pain to guide personalized approaches to treatment and inform future research.
Hospitalization in fibromyalgia: a cohort-level observational study of in-patient procedures, costs and geographical variation in England
Abstract Objectives Fibromyalgia is a complex, debilitating, multifactorial condition that can be difficult to manage. Recommended treatments are usually delivered in outpatient settings; evidence suggests that significant inpatient care occurs. We describe the scale and cost of inpatient care with a primary diagnostic code of fibromyalgia within the English National Health Service. Methods We conducted a cohort-level observational study of all patients admitted to hospital due to a diagnosis of fibromyalgia, between 1 April 2014 and 31 March 2018 inclusive, in the National Health Service in England. We used data from Hospital Episode Statistics Admitted Patient Care to study: the age and sex of patients admitted, number and costs of admissions, length of stay, procedures undertaken, class and type of admission, and distribution of admissions across clinical commissioning groups. Results A total of 24 295 inpatient admissions, costing £20 220 576, occurred during the 4-year study period. Most patients were women (89%) with peak age of admission of between 45 and 55 years. Most admissions were elective (92%). A number of invasive therapeutic procedures took place, including a continuous i.v. infusion (35%). There was marked geographical variation in the prevalence and cost of inpatient fibromyalgia care delivered across the country, even after accounting for clinical commissioning group size. Conclusions Many patients are admitted for treatment of their fibromyalgia and given invasive procedures for which there is weak evidence, with significant variation in practice and cost across the country. This highlights the need to identify areas of resource use that can be rationalized and diverted to provide more effective, evidence-based treatment.
Does obesity predict knee pain over fourteen years in women, independently of radiographic changes?
AbstractObjectiveTo examine longitudinal patterns in body mass index (BMI) over 14 years and its association with knee pain in the Chingford Study.MethodsWe studied a total of 594 women with BMI data from clinic visits at years (Y) 1, 5, 10, and 15. Knee pain at Y15 was assessed by questionnaire. Associations between BMI over 14 years and knee pain at Y15 were examined using logistic regression.ResultsBMI significantly increased from Y1 to Y15 (P < 0.0005) with medians (interquartile ranges) of 24.5 kg/m2 (22.5–27.2 kg/m2) and 26.5 kg/m2 (23.9–30.1 kg/m2), respectively. At Y15, 45.1% of subjects had knee pain. A greater BMI at Y1 (odds ratio [OR] 1.34, 95% confidence interval [95% CI] 1.05–1.69), at Y15 (OR 1.34, 95% CI 1.10–1.61), and change in BMI over 15 years (OR 1.40, 95% CI 1.00–1.93) were significant predictors of knee pain at Y15 (P < 0.05). BMI change was associated with bilateral (OR 1.61, 95% CI 1.05–1.76, P = 0.024) but not unilateral knee pain (OR 1.22, 95% CI 0.73–1.76, P = 0.298). The association between BMI change and knee pain was independent of radiographic knee osteoarthritis (OA). The strength of association between BMI and knee pain at Y15 was similar during followup measurements.ConclusionOver 14 years, a higher BMI predicts knee pain at Y15 in women, independently of radiographic knee OA. When adjusted, the association was significant in bilateral, not unilateral, knee pain, suggesting alternative pathologic mechanisms may exist. The longitudinal effect of BMI on knee pain at Y15 is equally important at any time point, which may assist reducing the population burden of knee pain.
Supervised Exercise plus Acupuncture for Moderate to Severe Knee Osteoarthritis: A Small Randomised Controlled Trial
Objectives Although total knee replacement (TKR) is cost effective and successful in most cases, patient-reported outcome measures demonstrate 20% of people remain unsatisfied at 1 year after a technically successful procedure. Our group has previously shown that patients with severe knee osteoarthritis (OA) awaiting surgery can achieve a short-term reduction in symptom severity when treated with acupuncture, and that a trend towards improved walking distance, as a measure of function, is achieved with preoperative supervised exercise. The aim of this study was to evaluate the effect of combined acupuncture and physiotherapy on preoperative and postoperative pain and function. Methods A total of 56 patients awaiting TKR surgery were randomised to receive either combined physiotherapy and acupuncture or a standardised exercise and advice leaflet. Pain and function were measured primarily using the Oxford Knee Score (OKS), with assessments at baseline prior to intervention, 6 and 12 weeks after intervention and at 3 months postoperatively. Results Due to the introduction of the 18-week waiting times target during this study, the required sample size was not achieved. There were no significant differences demonstrated between the control and treatment groups for OKS. Seven patients withdrew from surgery because of symptomatic improvement in their knees: six from the treatment group and one from the control group (OR 7.64, 95% CI 0.86 to 68.20). Conclusions This study demonstrated that the use of combined acupuncture and physiotherapy in the treatment of patients with moderate to severe knee OA preoperatively did not improve patient outcome postoperatively. As the study was underpowered, a larger trial is required to examine this result further.
The natural history of radiographic knee osteoarthritis: A fourteen‐year population‐based cohort study
AbstractObjectiveTo establish the natural history of radiographic knee osteoarthritis (OA) over 14 years in a community‐based cohort.MethodsWe examined women from the Chingford Women's Study, a community‐based cohort followed up for more than 14 years. We selected women for whom bilateral radiographs of the knees (with the legs in full extension) were obtained at approximately 5‐year intervals. Radiographs were scored for OA in a blinded manner, using Kellgren/Lawrence (K/L) grades. Descriptive statistics and odds ratios (ORs) were used to compare the incidence, worsening, and progression of radiographic knee OA.ResultsA complete radiography series was available for 561 of the original 1,003 subjects enrolled in the study. The median age of these subjects at baseline was 53 years (interquartile range 48–58 years). At baseline, 13.7% of the subjects had radiographic knee OA (K/L grade ≥2) in at least one knee, and the prevalence increased to 47.8% by year 15. The annual cumulative incidence of radiographic knee OA was 2.3% between baseline and year 15. The annual rates of disease progression and worsening between baseline and year 15 were 2.8% and 3.0%, respectively. Subjects with a K/L grade of 1 at baseline were more likely to experience worsening by year 15 compared with subjects with a baseline grade of 0 (OR 4.5, 95% confidence interval 2.7–7.4).ConclusionThis is the longest natural history study of radiographic knee OA to date. The results showed relatively low rates for the incidence and progression of radiographic knee OA; more than half of all subjects had no radiographic evidence of knee OA over a 15‐year period of time. Subjects with a baseline K/L grade of 1 were more likely than subjects with other baseline K/L grades to experience worsening of knee OA.
Prevalence of reported knee pain over twelve years in a community‐based cohort
AbstractObjectiveTo describe the temporal patterns of knee pain in a community‐based cohort over 12 years.MethodsData on self‐reported knee pain at 4 time points over 12 years were analyzed in participants from the Chingford Women's Study of osteoarthritis (OA) and osteoporosis. Pain status was defined as any pain in the preceding month and pain on most days in the preceding month. This status was used to classify participants according to pain patterns of asymptomatic, persistent, incident, or intermittent pain. Multinomial logistic regression was used to identify baseline predictors for each pain pattern.ResultsAmong the 489 women with complete followup data, the median age at baseline was 52 years (interquartile range [IQR] 48–58 years), the median body mass index (BMI) was 24.39 kg/m2 (IQR 22.46–27.20), and 11.7% of the women had a Kellgren/Lawrence radiographic OA severity grade of ≥2 in at least one knee. Among subjects reporting any pain in the preceding month versus those reporting pain on most days in the preceding month, 9% versus 2% had persistent pain, 24% versus 16% had incident pain, and 29% versus 18% had intermittent pain. A higher BMI was predictive of persistent pain (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.04–1.25) and incident pain (OR 1.10, 95% CI 1.02–1.18). The presence of radiographic knee OA was predictive of persistent pain (OR 3.70, 95% CI 1.34–10.28; P = 0.012), and reported knee injury was predictive of both persistent pain (OR 4.13, 95% CI 1.34–12.66; P = 0.013) and intermittent pain (OR 4.25, 95% CI 1.81–9.98; P = 0.001).ConclusionSignificant variability in the temporal fluctuation of self‐reported knee pain was seen in this community‐based prospective study over a period of 12 years, with few women consistently reporting knee pain at each time point. Distinct baseline predictors for each pain pattern were identified and may explain the observed heterogeneity of self‐reported knee pain when pain status is measured at only one time point.