Self-reported pain severity and use of cannabis and opioids in persons with HIV in an urban primary care setting in Northern California: A cross-sectional study.

Persons with HIV (PWH) experience high levels of pain. We examined the relationship of pain severity with use of cannabis and prescription opioids among PWH. This cross-sectional study evaluated associations between self-reported pain (moderate/severe vs mild/none) and cannabis and prescription opioid use in a primary care sample of PWH enrolled in an alcohol use treatment study at Kaiser Permanente, San Francisco. Prevalence ratios (PR) for moderate/severe pain associated with cannabis, opioid use, or both in the prior 30 days were obtained from Poisson regression models. Adjusted models included race/ethnicity, education, employment, HIV ribonucleic acid levels, depression, and anxiety. Overall, 614 PWH completed baseline questionnaires from May 2013 to May 2015, among whom 182/614 (29.6%) reported moderate/severe pain. The prevalence of moderate/severe pain varied by substances: 19.1% moderate/severe pain among study participants who reported neither cannabis or opioids, 30.2% for cannabis alone, 41.2% for opioids alone, and 60.9% for those reporting both substances. In adjusted models, compared with PWH who reported neither substance (reference), prevalence of moderate/severe pain was higher for those using cannabis alone (PR 1.54; 95% CI 1.13-2.09), opioids alone (PR 1.96; 95% CI 1.31-2.94), and those reporting both (PR 2.66; 95% CI 1.91-3.70). PWH who reported opioid and/or cannabis use were more likely to report moderate/severe pain compared with PWH who did not report use of these substances. To improve patient care, it is vital to assess patients' approaches to pain management including substance use and target appropriate interventions to reduce pain in PWH.

Rapid response nursing triage outcomes for COVID-19: factors associated with patient's participation in triage recommendations.

BACKGROUND: COVID-19 is an ongoing global health crisis with prevention and treatment recommendations rapidly changing. Rapid response telephone triage and advice services are critical in providing timely care during pandemics. Understanding patient participation with triage recommendations and factors associated with patient participation can assist in developing sensitive and timely interventions for receiving the treatment to prevent adverse health effects of COVID-19. METHODS: This cohort study aimed to assess patient participation (percentage of patients who followed nursing triage suggestions from the COVID hotline) and identify factors associated with patient participation in four quarterly electronic health records from March 2020 to March 2021 (Phase 1: 14 March 2020-6 June 2020; Phase 2: 17 June 2020-16 September 2020; Phase 3: 17 September 2020-16 December 2020; Phase 4: 17 December 2020-16 March 2021). All callers who provided their symptoms (including asymptomatic with exposure to COVID) and received nursing triage were included in the study. Factors associated with patient participation were identified using multivariable logistic regression analyses, including demographic variables, comorbidity variables, health behaviors, and COVID-19-related symptoms. RESULTS: The aggregated data included 9849 encounters/calls from 9021 unique participants. Results indicated: (1) 72.5% of patient participation rate; (2) participants advised to seek emergency department care had the lowest patient participation rate (43.4%); (3) patient participation was associated with older age, a lower comorbidity index, a lack of unexplained muscle aches, and respiratory symptoms. The absence of respiratory symptoms was the only factor significantly associated with patient participation in all four phases (OR = 0.75, 0.60, 0.64, 0.52, respectively). Older age was associated with higher patient participation in three out of four phases (OR = 1.01-1.02), and a lower Charlson comorbidity index was associated with higher patient participation in phase 3 and phase 4 (OR = 0.83, 0.88). CONCLUSION: Public participation in nursing triage during the COVID pandemic requires attention. This study supports using a nurse-led telehealth intervention and reveals crucial factors associated with patient participation. It highlighted the importance of timely follow-up in high-risk groups and the benefit of a telehealth intervention led by nurses serving as healthcare navigators during the COVID-19 pandemic.

A rapid homogenous bioassay for detection of thyroid-stimulating antibodies based on a luminescent cyclic AMP biosensor.

Graves' disease (GD) is an autoimmune disease caused by antibodies to the thyroid stimulating hormone receptor (TSHR). The FDA-cleared Thyretain™ TSI bioassay is a highly specific method to detect thyroid stimulating antibodies (TSAb/TSI) in the blood of patients with autoimmune thyroid disease (AITD), particularly GD. To simplify the workflow of this bioassay and to support a semi-quantitative result, we have generated a stable CHO-K1 cell line expressing both a chimeric TSH receptor (TSHR-Mc4) and a luciferase-based homogeneous cAMP biosensor (GS luciferase). Here, we describe a rapid, real-time, homogenous bioassay (Turbo™ TSI Bioassay) to directly assess the functional activity of TSI and produce results in International Units of IU/L. The Turbo™ TSI bioassay works by measuring changes in the intracellular cAMP level induced by a G-protein coupled receptor (G-PCR) signaling cascade which is triggered by the binding of TSI to the TSHR. Upon binding to cAMP, the GS luciferase reporter is activated through conformational changes and generates light that can be measured in intact cells with a luminometer. The LoD and LoQ of the assay were determined to be 0.016 IU/L and 0.03 IU/L, respectively and the preliminary assay cutoff was determined to be 0.024 IU/L by ROC analysis using the Thyretain™ TSI bioassay results as reference. The analytical performance of the Turbo™ TSI bioassay is comparable to the Thyretain™ TSI bioassay as evidenced by similar EC50 values for a TSHR stimulating monoclonal antibody (M22). The specificity of the Turbo™ TSI bioassay was demonstrated by showing no response to a high concentration of a human monoclonal TSHR blocking antibody (K1-70). The precision of the assay was excellent with an overall within-laboratory precision <15% CV. When testing 198 clinical samples, the positive and negative percent agreement between the Turbo™ TSI and the Thyretain™ TSI bioassays were 98.7% and 93.5%, respectively. While both bioassays yield equivalent analytical and clinical performances, the Turbo™ TSI bioassay is much simpler to perform. It does not require cell culture, sample dilution, washing or cell lysis steps, resulting in a dramatically reduced turnaround time from about 21 h to 60 min. In addition, the same cell line showed its capability of detecting thyroid blocking antibodies (TBAb/TBI) in a competitive format. The Turbo™ TSI bioassay is user-friendly and is a very promising advancement to aid the diagnosis of autoimmune thyroid disease (AITD).

Ubiquitin-protein ligases in muscle wasting.

Muscle wasting occurs when rates of protein degradation outstrip rates of protein synthesis. Accelerated rates of protein degradation develop in atrophying muscle largely through activation of the ubiquitin-proteasome pathway. The complexity of the ubiquitination process, however, has hampered our understanding of how this pathway is activated in atrophying muscles and which enzymes of the ubiquitin conjugation system are responsible. Recent studies demonstrate that two ubiquitin-protein ligases (E3s), atrogin-1/MAFbx and MuRF1 are critical in the development of muscle atrophy. Other experiments implicate E2(14k) and E3alpha, of the N-end rule pathway, as important players in the process. It seems likely that multiple pathways of ubiquitin conjugation are activated in parallel in atrophying muscle, perhaps to target for degradation specific classes of muscle proteins. The emerging challenge will be to define the protein targets for, as well as to develop inhibitors of, these E3s.