Are reallocations of time between physical activity, sedentary behaviour and sleep associated with low back pain? A compositional data analysis.

Objectives: The aim of this cross-sectional study was to explore the associations of reallocating time between moderate- to vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SB) and sleep with occurrence, frequency and intensity of low back pain (LBP) among adults using compositional isotemporal substitution analysis. Methods: A total of 2333 participants from the general adult population completed the Daily Activity Behaviours Questionnaire asking about their time-use composition consisting of sleep, SB, LPA and MVPA, and they self-reported their frequency and intensity of LBP in the past year. Results: Regression analyses adjusted for age, sex, body mass index, smoking, stress, education and socioeconomic status found that the time-use composition is associated with the frequency (p=0.009) and intensity of LBP (p<0.001). Reallocating time from SB or LPA to sleep was associated with lower frequency and intensity of LBP (p<0.05). Reallocating time from MVPA to sleep, SB or LPA and from SB to LPA was associated with a lower intensity of LBP (p<0.05). For example, reallocating 30 min/day from SB to sleep was associated with 5% lower odds (95% CI: 2% to 8%, p=0.001) of experiencing LBP more frequently, and 2% lower LBP intensity (95% CI: 1% to 3%, p<0.001). Conclusion: LBP sufferers may benefit from getting additional sleep and spending more time in LPA, while engaging less in SB and MVPA. These reallocations of time may be meaningful from clinical and public health perspectives.

Rituximab and Pyoderma Gangrenosum: An Investigation of Disproportionality Using a Systems Biology-Informed Approach in the FAERS Database.

BACKGROUND: Studies have found an increased risk of pyoderma gangrenosum associated with rituximab. The structural properties and pharmacological action of rituximab may affect the risk of pyoderma gangrenosum. Additionally, pyoderma gangrenosum is associated with autoimmune disorders for which rituximab is indicated. OBJECTIVE: We aimed to determine whether rituximab is disproportionally associated with pyoderma gangrenosum using a systems biology-informed approach. METHODS: Adverse event reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS, 2013-20). The Bayesian Confidence Propagation Neural Network Information Component was used to test for disproportionality. Comparators used to determine potential causal pathways included all other medicines, all medicines with a similar structure (monoclonal antibodies), all medicines with the same pharmacological target (CD20 antagonists) and all medicines used for the same indication(s) as rituximab. RESULTS: Thirty-two pyoderma gangrenosum cases were identified, 62.5% were female, with a median age of 48 years. There was an increased association of pyoderma gangrenosum with rituximab compared with all other medicines (exponentiated Information Component 6.75, 95% confidence interval (CI) 4.66-9.23). No association was observed when the comparator was either monoclonal antibodies or CD20 antagonists. Conditions for which an association of pyoderma gangrenosum with rituximab was observed were multiple sclerosis (6.68, 95% CI 1.63-15.15), rheumatoid arthritis (2.67, 95% CI 1.14-4.80) and non-Hodgkin's lymphoma (2.94, 95% CI 1.80-3.73). CONCLUSIONS: Pyoderma gangrenosum was reported more frequently with rituximab compared with all other medicines. The varying results when restricting medicines for the same condition suggest the potential for confounding by indication. Post-market surveillance of biologic medicines in  FAERS should consider a multi-faceted approach, particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.