Sleep and Pain : A Systematic Review of Studies of Mediation

DW is funded by a Versus Arthritis Foundation Fellowship [grant number 21742].Peer reviewedPublisher PD

Remote sampling of biomarkers of inflammation with linked patient generated health data in patients with rheumatic diseases:an Ecological Momentary Assessment feasibility study

BACKGROUND: People with rheumatic diseases experience troublesome fluctuations in fatigue. Debated causes include pain, mood and inflammation. To determine the relationships between these potential causes, serial assessments are required but are methodologically challenging. This mobile health (mHealth) study explored the viability of using a smartphone app to collect patient-reported symptoms with contemporaneous Dried Blood Spot Sampling (DBSS) for inflammation. METHODS: Over 30 days, thirty-eight participants (12 RA, 13 OA, and 13 FM) used uMotif, a smartphone app, to report fatigue, pain and mood, on 5-point ordinal scales, twice daily. Daily DBSS, from which C-reactive Protein (CRP) values were extracted, were completed on days 1–7, 14 and 30. Participant engagement was determined based on frequency of data entry and ability to calculate within- and between-day symptom changes. DBSS feasibility and engagement was determined based on the proportion of samples returned and usable for extraction, and the number of days between which between-day changes in CRP which could be calculated (days 1–7). RESULTS: Fatigue was reported at least once on 1085/1140 days (95.2%). Approximately 65% of within- and between-day fatigue changes could be calculated. Rates were similar for pain and mood. A total of 287/342 (83.9%) DBSS, were returned, and all samples were viable for CRP extraction. Fatigue, pain and mood varied considerably, but clinically meaningful (≥ 5 mg/L) CRP changes were uncommon. CONCLUSIONS: Embedding DBSS in mHealth studies will enable researchers to obtain serial symptom assessments with matched biological samples. This provides exciting opportunities to address hitherto unanswerable questions, such as elucidating the mechanisms of fatigue fluctuations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05723-w

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Central sensitization predicts greater fatigue independently of musculoskeletal pain

Objectives: to test whether central sensitization was associated with greater fatigue, independently of musculoskeletal pain.Methods: 2477 prospective cohort study participants completed a baseline questionnaire comprising the Chalder Fatigue Scale (CFQ), pain, demographics, physical activity, anxiety, depression and medication use. In a clinical assessment of 290 (11.7%) participants, central sensitization was measured by the wind-up ratio test at the hand (WUR-H) and foot (WUR-F). Bioelectric impedance determined proportion body fat. All participants were followed up 12 months later, at which time they completed the CFQ. Linear regression, with inverse probability sampling weights, tested the relationship between WUR at baseline and CFQ at 12 months, adjusted for baseline CFQ, demographics, lifestyle factors, mental health and baseline pain.Results: at baseline, the median interquartile range WUR-H and WUR-F were similar (2.3 (1.5, 4.0) and 2.4 (1.6, 3.9) respectively) and did not differ by sex (difference WUR-H: −0.29, 95% confidence interval −1.28–0.71; WUR-F: −0.57 (−1.50–0.36) or age(WUR-H: −0.53, −1.49–0.43; WUR-F:−0.08, −0.98–0.82). WUR-H scores (β = 0.11, 95% confidence interval: 0.07–0.16) and WUR-F scores (0.13, 0.08–0.17) were positively associated with CFQ scores at follow-up, independently of baseline CFQ and other covariates. These associations were not explained by baseline pain.Conclusion: fatigue was predicted by central sensitization, independently of the presence of pain. For those seeking to treat fatigue, the benefit of interventions that reduce central sensitization should be investigated

Maximizing engagement in mobile health studies: lessons learned and future directions

The widespread availability of smartphones, tablets, and apps presents an exciting opportunity for epidemiologic research.Although promising, the key challenge of all apps (both for research and nonresearch) is the high attrition rate of participants and users.Any engagement strategies used should consider usability of technology, push or motivating factors, and the need for personal contact with study personnel (not just technology) and study support.Particular benefits to long-term engagement may occur through the use of real-time data monitoring and passive monitoring and by providing personalized study feedback.Future studies should consider adopting and advancing these approaches at an early stage of study design to maximize patient engagement

Patients receiving anti-TNF therapies experience clinically important improvements in RA-related fatigue : results from the British Society of Rheumatology Biologics Register for Rheumatoid Arthritis

Acknowledgements The authors would like to thank the University of Manchester for access to the BSRBR-RA data and the BSR staff and Steering Committee for assistance with manuscript preparation. The BSRBR-RA is supported by a research grant from the BSR to the University of Manchester, which is indirectly funded by Schering Plough, Wyeth Laboratories, Abbott Laboratories and Amgen. Funding: This work forms part of K.L.D.’s Ph.D. dissertation, which is funded by the Institute of Applied Health Sciences, University of Aberdeen. Disclosure statement: N.B. has received research support from and/or served on advisory boards for Pfizer, MSD and GSK. All other authors have declared no conflicts of interest.Peer reviewedPostprin

Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumatoid Arthritis

The authors have no conflicts of interest to disclose. This work was supported by the Institute of Applied Health Sciences, University of Aberdeen, who provided KD’s PhD studentship. The BSR commissioned the BSRBR-RA as a UK-wide national project to investigate the safety of biologic agents in routine medical practice. BSR receives restricted income from UK pharmaceutical companies, presently Abbott Laboratories, Merck, Pfizer, Roche, UCB and SOBI. This income finances a wholly separate contract between the BSR and the University of Manchester who provide and oversee the BSRBR-RA data collection, management and analysis service. The principal investigators and their team have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution.Peer reviewedPostprintPostprintPostprin

Examining Changes in Central and Peripheral Pain as Mediates of Fatigue Improvement : Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

ROLE OF THE STUDY SPONSOR The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis data collection, management, and analysis service, funded by UK pharmaceutical companies, is overseen by The University of Manchester. The principal investigators and their team had full academic freedom and were able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation, and publication were made autonomously of any industrial contribution.Peer reviewedPostprin