Methods applied to neonatal dried blood spot samples for secondary research purposes: a scoping review.

This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.

Classification of long-term condition patterns in rheumatoid arthritis and associations with adverse health events: a UK Biobank cohort study.

Purpose: We aimed to classify individuals with RA and ≥2 additional long-term conditions (LTCs) and describe the association between different LTC classes, number of LTCs and adverse health outcomes. Methods: We used UK Biobank participants who reported RA (n=5,625) and employed latent class analysis (LCA) to create classes of LTC combinations for those with ≥2 additional LTCs. Cox-proportional hazard and negative binomial regression were used to compare the risk of all-cause mortality, major adverse cardiac events (MACE), and number of emergency hospitalisations over an 11-year follow-up across the different LTC classes and in those with RA plus one additional LTC. Persons with RA without LTCs were the reference group. Analyses were adjusted for demographic characteristics, smoking, BMI, alcohol consumption and physical activity. Results: A total of 2,566 (46%) participants reported ≥2 LTCs in addition to RA. This involved 1,138 distinct LTC combinations of which 86% were reported by ≤2 individuals. LCA identified 5 morbidity-classes. The distinctive condition in the class with the highest mortality was cancer (class 5; HR 2.66 95%CI (1.91-3.70)). The highest MACE (HR 2.95 95%CI (2.11-4.14)) and emergency hospitalisations (rate ratio 3.01 (2.56-3.54)) were observed in class 3 which comprised asthma, COPD & CHD. There was an increase in mortality, MACE and emergency hospital admissions within each class as the number of LTCs increased. Conclusions: The risk of adverse health outcomes in RA varied with different patterns of multimorbidity. The pattern of multimorbidity should be considered in risk assessment and formulating management plans in patients with RA.

Association between risk, duration and cause of hospitalisations in people with rheumatoid arthritis and multimorbidity in the UK Biobank and Scottish Early Rheumatoid Arthritis (SERA) cohorts: Longitudinal observational study.

OBJECTIVES: To investigate association between presence of multimorbidity in people with established and early rheumatoid arthritis (RA) and risk, duration and cause of hospitalisations. DESIGN: Longitudinal observational study. SETTING: UK Biobank, population-based cohort recruited between 2006 and 2010, and the Scottish Early Rheumatoid Arthritis (SERA), inception cohort recruited between 2011 and 2015. Both linked to mortality and hospitalisation data. PARTICIPANTS: 4757 UK Biobank participants self-reporting established RA; 825 SERA participants with early RA meeting the 2010 ACR/EULAR classification criteria. Participants stratified by number of long-term conditions (LTCs) in addition to RA (RA only, RA + 1 LTC and RA + ≥ 2 LTCs) and matched to five non-RA controls. MAIN OUTCOME MEASURES: Number and duration of hospitalisations and their causes. Incidence rate ratios (IRR) and 95% confidence intervals (CI) calculated using negative binomial regression models. RESULTS: Participants with RA + ≥ 2 LTCs experienced higher hospitalisation rates compared to those with RA alone (UK Biobank: IRR 2.10, 95% CI 1.91 to 2.30; SERA: IRR 1.74, 95% CI 1.23 to 2.48). Total duration of hospitalisation in RA + ≥ 2 LTCs was also higher (UK Biobank: IRR 2.48, 95% CI 2.17 to 2.84; SERA: IRR 1.90, 95% CI 1.07 to 3.38) than with RA alone. Rate and total duration of hospitalisations was higher in UK Biobank RA participants than non-RA controls with equivalent number of LTCs. Hospitalisations for respiratory infection were higher in early RA than established RA and were the commonest cause of hospital admission in early RA. CONCLUSIONS: Participants with established or early RA with multimorbidity experienced a higher rate and duration of hospitalisations than those with RA alone and with non-RA matched controls.

Examining the Relationship Between Rheumatoid Arthritis, Multimorbidity, and Adverse Health-Related Outcomes: A Systematic Review.

OBJECTIVE: Multimorbidity (the coexistence of two or more long-term conditions) is highly prevalent in people who have rheumatoid arthritis (RA). The present work systematically reviewed the literature to determine the effect of multimorbidity on all-cause mortality, functional status, and quality of life in RA. METHODS: Six electronic databases were searched: CINAHL, The Cochrane Library, Embase, Medline, PsycINFO, and Scopus. Full-text longitudinal observational studies in English were selected. Quality appraisal of studies was undertaken using the Cochrane-developed QUIPS tool and a narrative synthesis of findings conducted. RESULTS: The search strategy identified 5,343 articles, with 19 studies meeting the inclusion criteria. Nine studies had mortality as an outcome, 9 reported functional status and/or quality of life, and 1 study reported both mortality and functional status. The number of participants ranged from 183 to 18,485, with studies conducted between 1985 and 2018. The mean age of participants ranged from 52.0 to 66.6 years, and 60.0-88.0% were female. Nine studies showed a significant association between multimorbidity and higher risk of mortality in people with RA. Ten studies reported significant associations between multimorbidity and reduced functional status in RA. Three studies also showed a further association with reduced quality of life. Only one study investigated the influence of mental health comorbidities on outcomes. CONCLUSION: Our review findings indicate that multimorbidity is a significant predictor for higher mortality and poorer functional status/quality of life in people with RA and should be considered in clinical management plans.

Examining the relationship between rheumatoid arthritis, multimorbidity and adverse health-related outcomes: A systematic review protocol.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. OBJECTIVE: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. DESIGN: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. CONCLUSIONS: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756.

Patterns of multimorbidity and their effects on adverse outcomes in rheumatoid arthritis: a study of 5658 UK Biobank participants.

OBJECTIVE: To investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA). DESIGN: Population-based longitudinal cohort study. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants (n=502 533) aged between 37 and 73 years old. PRIMARY OUTCOME MEASURES: Primary outcome measures were risk of all-cause mortality and MACE. METHODS: We examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox's proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor. RESULTS: 75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports. CONCLUSION: Those with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.