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Drug-induced hyperuricemia and gout present an increasingly prevalent problem in clinical practice. Herein, we review the urate-lowering or urate-raising effects of commonly used agents. We performed a PubMed search using the terms gout, urate, and medication, along with the specific agents/classes described herein. Reports were reviewed until 2022, and original studies were considered if they primarily or secondarily reported the effects of 1 or more drugs on serum urate level. Previous reviews were assessed for references to additional studies that described urate-altering effects of medications. Urate-changing drugs are summarized regarding their magnitude of effect, mechanism of action, and clinical significance. Potentially urate-lowering drugs include angiotensin II receptor blockers, calcium channel blockers, high-dose aspirin and salicylates, some nonsalicylate nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, sodium-glucose cotransporter 2 inhibitors, statins, and fenofibrate. Potentially urate-increasing drugs discussed include diuretics, β-blockers, insulin, pyrazinamide, ethambutol, calcineurin inhibitors, low-dose aspirin, testosterone, and lactate. In patients who have or are at risk for hyperuricemia or gout, an increased awareness of drugs that affect serum urate level may allow for prescribing that effectively treats the indicated problem while minimizing adverse effects on hyperuricemia and gout.

Objectives Glucocorticoids (GCs) (‘steroids’) are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. Methods Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. Results Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire. Conclusion We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM.

Objective Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions. Methods The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set. Results 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as “mandatory in specific circumstances”. The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders. Conclusion A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Background/Aims Glucocorticoids (GCs) are widely used to treat inflammatory rheumatic diseases. GCs carry a range of adverse effects of concern to patients and clinicians. The objective of this study was to explore the impact of GC therapy on health-related quality of life (HRQoL) during treatment for rheumatic diseases, as a basis for development of a patient-reported outcome measure (PROM) to be used in clinical trials and practice. Methods Patients from the UK, USA and Australia who were treated with GCs in the last two years for a rheumatic condition were invited to take part in semi-structured qualitative interviews. A steering committee of patient research partners, clinicians and methodologists devised an initial conceptual framework, which informed interview prompts and cues. Interviews identified physical and psychological symptoms and salient aspects of HRQoL in relation to treatment with GCs. Purposive sampling was used to include a range of demographic and disease features. The interview data were organised using NVivo, and inductive analysis identified initial themes and domains. Candidate questionnaire items were developed and refined using cognitive interviewing, linguistic assessment, and input from patient research partners. Results Sixty semi-structured qualitative interviews were conducted (UK n = 34, USA n = 10, Australia n = 16). Mean participant age was 58 years; 39 (66.1%) were female. Detailed demographic and GC use information is provided in Table 1. The following initial domains were developed to identify key themes relating to treatment using GCs and their impact on HRQoL: benefits of steroids; physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation and on relationships. Forty-one candidate questionnaire items were developed from the individual themes. These were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews with patients with a range of rheumatic conditions from the UK, USA and Australia, and a linguistic translatability assessment, to define a draft questionnaire. Conclusion This international qualitative study underpins the development of candidate items for a treatment-specific PROM for patients with rheumatic diseases. The draft questionnaire is now ready for testing in an online large-scale survey to determine the final scale structure, possible item reduction, and measurement properties. Disclosure S. Bridgewater: None. M.A. Shepherd: None. J. Dawson: None. P. Richards: None. C. Silverthorne: None. M. Ndosi: None. C. Almeida: None. R.J. Black: None. J.T.L. Cheah: None. E. Dures: None. N. Ghosh: None. E.A. Hoon: None. S. Lyne: None. I. Navarro-Millan: None. D. Pearce-Fisher: None. C. Ruediger: None. J. Tieu: None. K. Yip: None. S. Mackie: None. S. Goodman: None. C. Hill: None. J.C. Robson: None.

Purpose of review Hyperuricemia is highly prevalent, affecting approximately 38 million individuals in the United States. However, the significance of asymptomatic hyperuricemia - hyperuricemia in the absence of gout - continues to be debated. Recent findings Asymptomatic hyperuricemia results in monosodium urate crystal deposition in tissues, which may promote chronic inflammation. Intracellularly, hyperuricemia inhibits the master regulator adenosine monophosphate (AMP)-associated protein kinase and may condition innate immune responses through durable epigenetic modifications. At the population level, asymptomatic hyperuricemia is associated with multiple comorbidities, including hypertension, chronic kidney disease, coronary artery disease, and diabetes; limitations of these studies include that most are retrospective and some do not rigorously distinguish between asymptomatic hyperuricemia and gout. Treatment studies suggest that urate lowering may reduce the risk of incidence or progression of some of these comorbidities; unfortunately, many of these treatment studies are small or flawed, and not all study results are consistent. Summary Accumulating evidence suggests that asymptomatic hyperuricemia contributes to the comorbidities with which it associates and that proper asymptomatic hyperuricemia treatment may reduce future risk. Additional prospective trials are needed to definitely establish causality and support decision-making as to whether, and which patients with asymptomatic hyperuricemia would warrant urate-lowering treatment.

Background Postprandial distress syndrome manifests as a feeling of fullness and early satiation that can significantly reduce the quality of life of the patients. In Chinese medicine (CM), the syndrome is traditionally regarded as the Wei-Pi syndrome, and Banxia Xiexin decoction (BXD) has been used in the empirical treatment of the same for a long time. The current study aims to evaluate the efficacy of modified BXD in the management of Wei-Pi syndrome. Methods/design A randomized, waitlist-controlled trial will be conducted. A total of 84 patients with Wei-Pi syndrome will be randomized into the BXD or waitlist control group in a ratio of 1:1. The patients in the BXD group will receive the semi-individualized BXD on the basis of the syndrome differentiation in CM, for a duration of 3 weeks and will be under follow-up for further 3 weeks after the completion of therapy. Conversely, the patients in the waitlist control group will undergo the same intervention and follow-up after a 3-week waiting period. In the current study, the primary outcome will be the variation in the scores pertaining to the global scale of the Quality of Life Questionnaire for Functional Digestive Disorders after 3 weeks. The secondary outcomes include the variations in the scores pertaining to the Hospital Anxiety and Depression Scale and the EuroQoL 5-dimension 5-level Questionnaire and the results of the liver and kidney function tests. Discussion This trial will assess the efficacy of modified BXD in improving the clinical symptoms and quality of life of the patients suffering from Wei-Pi syndrome. Trial registration ClinicalTrials.govNCT04398888. Registered on May 21, 2020

Purpose of review This review highlights the available data describing racial and ethnic health disparities among patients with rheumatoid arthritis in the United States from an epidemiological, disease activity, and wider socioeconomic standpoint. Recent findings Despite centralized government initiatives to include more underrepresentative minority populations into research, many of the studies that examined rheumatoid arthritis still fail to include sizeable cohorts of races or ethnic groups other than whites. Evidence is slowly mounting that individual, provider, and system-level barriers exist and contribute to unequal care that leads to poorer outcomes amongst patients with rheumatoid arthritis. As rheumatoid arthritis is a progressive disease, early treatment is crucial to delay functional decline - a narrow window for many minority patients who are disproportionality affected by disability. Summary To combat the inequality that exists amongst rheumatoid arthritis patients we must focus on why discrepancies exist on every level, system, physician, patient, and illness. Further research is needed to tease the complex interplay between race, social economic status, medical access, and outcomes to explain the disparities found in rheumatoid arthritis.

Additional file 1. Participant information sheet and consent form.

Cyclic loading leads to interfacial fatigue of a graphene/polymer contact and multimode fracture of the graphene., Graphene is often in contact with other materials through weak van der Waals (vdW) interactions. Of particular interest is the graphene-polymer interface, which is constantly subjected to dynamic loading in applications, including flexible electronics and multifunctional coatings. Through in situ cyclic loading, we directly observed interfacial fatigue propagation at the graphene-polymer interface, which was revealed to satisfy a modified Paris’ law. Furthermore, cyclic loading through vdW contact was able to cause fatigue fracture of even pristine graphene through a combined in-plane shear and out-of-plane tear mechanism. Shear fracture was found to mainly initiate at the fold junctions induced by cyclic loading and propagate parallel to the loading direction. Fracture mechanics analysis was conducted to explain the kinetics of an exotic self-tearing behavior of graphene during cyclic loading. This work offers mechanistic insights into the dynamic reliability of graphene and graphene-polymer interface, which could facilitate the durable design of graphene-based structures.

Osteoarthritis is a common debilitating condition affecting a substantial portion of the population and is an accepted consequence of ageing and overuse. Whilst surgical interventions are a definitive approach, most cases are managed medically with analgesia. Pharmacological therapies have included acetaminophen, non-steroidal anti-inflammatory drugs and opiates. Although significant controversies exist in the use of opioids for chronic musculoskeletal pain, many leading guidelines continue to recommend its use despite increasing evidence to suggest an increase in addiction, morbidity and mortality. With the opiate crisis growing, we re-examine the role opiates have in this chronic condition and current data, and briefly evaluate alternative therapies.

The subsurface imaging capabilities of atomic force acoustic microscopy (AFAM) was investigated by imaging graphite flakes suspended over holes in a silicon dioxide substrate. The graphite thickness and the hole size were varied to determine the detection limit on the maximum graphite thickness and the smallest detectable hole size. Parameters including operating frequency, eigenmode, contact force, and cantilever stiffness were investigated for their influence of defect detection. AFAM was reliably able to detect 2.5 μm diameter holes through a maximum graphite thickness of 570 nm and sub 100 nm holes through 140 nm of graphite. The smallest detectable defect size was a 50 nm hole covered by an 80 nm thick graphite flake. Increasing the graphite thickness and decreasing the hole size both resulted in a decrease in subsurface contrast. However, the non-linear trend observed from increasing the graphite thickness indicates thickness has a greater effect on subsurface defect detection than variations in defect size. Through investigating various parameters, we have found certain cases to increase the observed contrast of the embedded subsurface holes, however the smallest detectable defect size remained the same. This technique's ability to reveal sub 100 nm defects buried under graphite has previously only been demonstrated in much softer polymer systems.

Photothermal excitation of the cantilever for use in subsurface imaging with atomic force microscopy was compared against traditional piezoelectric excitation. Photothermal excitation alleviates issues commonly found in traditional piezoelectrics such as spurious resonances by producing clean resonance peaks through direct cantilever excitation. A calibration specimen consisting of a 3 × 3 array of holes ranging from 200 to 30 nm etched into silicon and covered by graphite was used to compare these two drive mechanisms. Photothermal excitation exhibited a signal-to-noise ratio as high as four times when compared to piezoelectric excitation, utilizing higher eigenmodes for subsurface imaging. The cleaner and sharper resonance peaks obtained using photothermal excitation revealed all subsurface holes down to 30 nm through 135 nm of graphite. In addition, we demonstrated the ability of using photothermal excitation to detect the contact quality variation and evolution at graphite-polymer interfaces, which is critical in graphene-based nanocomposites, flexible electronics, and functional coatings.

Carmustine is a nitrosurea alkylating agent predominantly used at Peter MacCallum Cancer Centre as part of the autologous stem cell transplant induction regimens Stanford BCNU and BEAM. Acute infusion reactions were anecdotally reported to be higher than the reported rates of 10%, and it was suggested that the rate of infusion being employed was excessive. Some references suggest maximum infusion rates of 3 mg/m(2)/min for carmustine, a rate which is exceeded in the 2-h infusions used for Stanford BCNU, but not with BEAM.A retrospective audit was conducted in 64 patients (57 Stanford BCNU, 7 BEAM) who had received these regimens between January 2009 and November 2010.Rates of infusion reaction to carmustine were higher than literature values, with reactions in Stanford BCNU (94.7%) being significantly higher than for BEAM (28.6%; P = 0.0003). These findings have resulted in a change of administration of carmustine in Stanford BCNU from 2 to 3 h. Further studies plan to compare the incidence of infusion reactions before and after the change in administration rates.Patients receiving rapid infusion of carmustine in the Stanford BCNU regimen for stem cell conditioning have a high rate of infusion reaction. A maximum rate of 3 mg/m(2)/min is recommended.

Extraspinal causes of radicular pain are rare and are in danger of being overlooked. Here, we present a patient with pain radiating into the posterior thigh and lateral calf. Although initial differential diagnosis included lumbar herniated nucleus pulposus, further imaging revealed the presence of gluteus maximus calcific tendonosis. After physical therapy and a potent oral steroid regimen, the pain gradually resolved and the patient was able to return to full activity.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein); U01HG004695 (E. Birney); U54HG004563 (G. E. Crawford); U54HG004557 (T. R. Gingeras); U54HG004555 (T. J. Hubbard); U41HG004568 /n(W. J. Kent); U54HG004576 (R. M. Myers); U54HG004558 (M. Snyder);/nU54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker); RC2HG005591 and R01HG003700 (M. C. Giddings); R01HG004456-03 (Y. Ruan); U01HG004571 (S. A. Tenenbaum); U01HG004561 (Z. Weng); RC2HG005679 (K. P. White). This project was supported in part by American Recovery and/nReinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591,R01HG003541, U01HG004561, RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research/nProgram of the NHGRI (L. Elnitski, ZIAHG200323; E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California.

To investigate the surface roughness changes of newer esthetic dental restorative materials with aging and acid erosion in a simulated oral environment.The materials included two viscous conventional glass ionomer cements originally marketed for the ART approach, one resin-modified glass ionomer cement and two resin composites. Ten specimens for each material were prepared according to the manufacturers' instructions, then each specimen was immersed in 2 ml of buffered artificial saliva at 37 degrees C for three weeks. For each material, five specimens (Group B) were then coated with 1.23% acidulated phosphate fluoride (APF) gel for four minutes, rinsed and immersed again in artificial saliva for another three weeks. Gel was not applied to the Group A specimens. For each material, the surface roughness of an additional three fresh specimens and those from Groups A and B were evaluated using a profilometer and SEM.The resin composites showed the least effects of acidic corrosion on their surface texture. The viscous glass ionomer cements showed the greatest changes, with significantly increased surface roughness p0.001).The immersion of two newer viscous GICs in a buffered artificial saliva and the single application of APF gel resulted in significantly rougher surfaces over a relatively short six-week period.

Night vision devices are important tools that extend the operational capability of military and civilian flight operations. Although these devices enhance some aspects of night vision, they distort or degrade other aspects. Scintillation of the NVG signal at low light levels is one of the parameters that may affect pilot performance. We have developed a parametric model of NVG image scintillation. Measurements were taken of the output of a representative NVG at low light levels to validate the model and refine the values of the embedded parameters. A simple test environment was created using a photomultiplier and an oscilloscope. The model was used to create sequences of simulated NVG imagery that were characterized numerically and compared with measured NVG signals. The sequences of imagery are intended for use in laboratory experiments on depth and motion-in-depth perception.

Compound eyes are a highly successful natural solution to the issue of wide field of view and high update rate for vision systems. Applications for an electronic implementation of a compound eye sensor include high-speed object tracking and depth perception. In this paper we demonstrate the construction and operation of a prototype compound eye sensor which currently consists of up to 20 eyelets, each of which forms an image of approximately 150 pixels in diameter on a single CMOS image sensor. Post-fabrication calibration of such a sensor is discussed in detail with reference to experimental measurements of accuracy and repeatability.