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Introduction: Changes in plasma concentrations of anti-inflammatory cytokines, such as interleukin-6 (IL-6) and IL-10, after acute resistance exercise (RE) have been widely explored. Whether observed changes in plasma cytokine concentration correspond to the activation of anti-inflammatory signaling pathways in immune cells after acute RE is unknown. This study aimed to determine if changes in plasma cytokines after acute RE resulted in the activation of anti- inflammatory signaling pathways in peripheral blood mononuclear cells (PBMC). Methods: Healthy young males (N = 16; age = 23.5 ± 2.7 yr; BMI = 22.4 ± 1.7 kg·m-2) participated in a single session of whole-body RE (4 sets of 4 different exercises at 70% 1-repetition maximum with the last set to failure) and a sedentary control (CON) condition in a randomized crossover design. Blood samples were collected at several time points before and after the exercise bout. Results: Higher plasma IL-6, IL-10, and IL-1 RA concentrations were observed after RE compared with CON. Phosphorylation of STAT3 and protein expression of SOCS3 in PBMC were increased in RE compared with CON. The elevation of plasma IL-6, but not IL-10, coincided with the activation of STAT3 signaling in PBMC. Conclusions: These results highlight a potential mechanism by which RE may exert anti-inflammatory actions in circulating immune cells. [ABSTRACT FROM AUTHOR]

Dapsone, initially synthesized for textile dyeing, gained recognition in the 1930s for its antibacterial properties, leading to its utilization in dermatology for leprosy and dermatitis herpetiformis. Despite US Food and Drug Administration (FDA) approval for these conditions, dapsone's off-label uses have expanded, making it a valuable option in various dermatologic conditions. This review seeks to highlight the common uses of dapsone in its FDA indications and off-label indications. Diseases in which dapsone is considered first-line therapy or adjunctive therapy are reviewed, with highlights from the resources included. An overview of dapsone's pharmacokinetics, pharmacodynamics, indications, dosages, and safety profile are also reviewed. Dapsone's versatility and safety profile make it a cost-effective treatment option in dermatology, particularly for patients with limited access to specialized medications. Ongoing clinical trials are also described exploring dapsone's efficacy in novel dermatologic uses. Dapsone has been a valuable adjunctive therapy across various dermatologic conditions for years and evidence for its use continues to expand. [ABSTRACT FROM AUTHOR]

The article examines the relationship between biologic treatments for psoriasis and the risk of developing depression, based on a retrospective analysis of U.S. administrative claims data. Topics include the reduced incidence of depression among patients using biologics compared to conventional treatments, the relative risk reduction associated with different classes of biologics, and the implications of these findings for future treatment strategies.

Background: The management of pediatric dermatological conditions such as alopecia areata (AA), psoriasis, atopic dermatitis (AD), and hidradenitis suppurativa (HS) has significantly evolved with the introduction of biologics and small molecule targeted therapies. The advancement in understanding the immunopathogenesis of these chronic skin conditions has led to the development and approval of novel biologics and small molecule therapies. Initially approved by the United States Food and Drug Administration (FDA) for adults, most of these therapies are now being evaluated in clinical trials for safety and efficacy in adolescents and children, expanding new treatment options for pediatric patients. The role of the FDA in drug approval is multifaceted from drug inception, ensuring that research, data, and evidence show that the proposed drug is effective and safe for the intended use. Objective: The goal of this review article is to provide an overview of the recently FDA-approved and potential biologic and oral small molecule therapies in clinical trials for AA, psoriasis, AD, and HS in pediatric patients. Methods: The search for this review included keywords in ClinicalTrials.gov, PubMed, and Google Scholar for the latest research and clinical trials relevant to these conditions and treatments without the PRISMA methodology. Results: For pediatric AA, ritlecitinib is FDA-approved, while baricitinib and updacitinib are in phase 3 clinical trials for pediatric approval. The FDA-approved drugs for pediatric psoriasis include secukinumab, ustekinumab, ixekizumab, etanercept, and apremilast. Other phase 3 clinical trials for pediatric psoriasis include risankizumab, guselkumab, tildrakizumab, brodalumab, and deucravacitinib. For pediatric AD, the FDA-approved drugs are dupilumab, tralokinumab, abrocitinib, and upadacitinib, with many other drugs in phase 3 trials. Adalimumab is an FDA-approved biologic for pediatric HS, with various clinical trials ongoing for adults. The approved biologics and small molecule therapies had higher efficacy and improved safety profiles compared to traditional medications. Conclusions: With numerous ongoing trials, the success of these clinical trials could lead to their inclusion in treatment guidelines for these chronic skin conditions. Biologics and small molecule therapies offer new avenues for effective disease management, enabling personalized therapeutic interventions and improving pediatric health outcomes. [ABSTRACT FROM AUTHOR]

Objective: We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)–23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic‐naive or had inadequate response to tumor necrosis factor inhibitors (TNFi‐IR). Methods: Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic‐naive (n = 251) and TNFi‐IR (n = 93) subgroups identified in the pooled DISCOVER‐1/DISCOVER‐2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2‐point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups. Results: Baseline IL‐22, TNFα, and beta defensin‐2 (BD‐2) levels were significantly lower in biologic‐naive than in TNFi‐IR participants. With guselkumab, week 24 IL‐17A, IL‐17F, IL‐22, serum amyloid A, C‐reactive protein, IL‐6, and BD‐2 levels were significantly reduced from baseline in biologic‐naive and TNFi‐IR participants (≥1.4‐fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL‐17A, IL‐17F, BD‐2 in biologic‐naive PASI 90 responders; IL‐17A, BD‐2 in TNFi‐IR IGA 0/1 responders; IL‐22, BD‐2 in TNFi‐IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi‐IR ACR20 responders. Conclusion: Guselkumab modulates IL‐23 signaling and provides consistent pharmacodynamic effects in both biologic‐naive and TNFi‐IR PsA patients. Significantly elevated baseline IL‐22, TNFα, and BD‐2 levels and associations between baseline IL‐22, IL‐17A, and BD‐2 levels and skin responses to guselkumab suggest greater dysregulation of IL‐23/Th17 signaling in patients with TNFi‐IR. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) can arise from a variety of factors, including inflammation, meibomian gland dysfunction (MGD), and neurosensory abnormalities. Individuals with DED may exhibit a range of clinical signs, including tear instability, reduced tear production, and epithelial disruption, that are driven by different pathophysiological contributors. Those affected often report a spectrum of pain and visual symptoms that can impact physical and mental aspects of health, placing an overall burden on an individual's well-being. This cumulative impact of DED on an individual's activities and on society underscores the importance of finding diverse and effective management strategies. Such management strategies necessitate an understanding of the underlying pathophysiological mechanisms that contribute to DED in the individual patient. Presently, the majority of approved therapies for DED address T cell-mediated inflammation, with their tolerability and effectiveness varying across different studies. However, there is an emergence of treatments that target additional aspects of the disease, including novel inflammatory pathways, abnormalities of the eyelid margin, and neuronal function. These developments may allow for a more nuanced and precise management strategy for DED. This review highlights the recent pharmacological advancements in DED therapy in the United States. It discusses the mechanisms of action of these new treatments, presents key findings from clinical trials, discusses their current stage of development, and explores their potential applicability to different sub-types of DED. By providing a comprehensive overview of products in development, this review aims to contribute valuable insights to the ongoing efforts in enhancing the therapeutic options available to individuals suffering from DED. [ABSTRACT FROM AUTHOR]

Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx®), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis. Plain Language Summary: Psoriatic arthritis is a chronic, painful, inflammatory condition that can involve peripheral and axial joints, skin and nails, and can lead to structural joint damage. Several disease-modifying antirheumatic drugs (DMARDs), including biologicals (bDMARDs) that target various inflammatory cytokines, are approved for psoriatic arthritis. However, many patients do not respond or lose response to these treatments. Bimekizumab (Bimzelx®), an inhibitor of both interleukin (IL)-17A and IL-17F, is approved for the treatment of psoriatic arthritis in the EU, Great Britain and Japan. In clinical trials, bimekizumab improved the signs and symptoms of psoriatic arthritis across key disease domains compared with placebo, including the proportion of patients achieving ≥ 50% response in the American College of Rheumatology criteria. Bimekizumab was efficacious whether patients were naïve to bDMARDs or previously had an inadequate response to or did not tolerate tumour necrosis factor (TNF) α inhibitors. Clinical responses were sustained long-term (up to 3 years). Bimekizumab was generally well tolerated, with the most common adverse events being infections (such as nasopharyngitis, upper respiratory tract infection and oral candidiasis), headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Introduction: Renal colic is frequently treated with opioids; however, narcotic analgesic use can lead to dependence and abuse. We evaluated use trends of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management of kidney stones in United States emergency departments (EDs) from 2015 to 2021. Methods: Kidney stone encounters were identified using National Hospital Ambulatory Medical Care Survey data. We applied a multistage survey weighting procedure to account for selection probability, nonresponse, and population weights. Medication use trends were estimated through logistic regressions on the timing of the encounter, adjusted for selected demographic and clinical characteristics. Results: Between 2015 and 2021, there were an estimated 9,433,291 kidney stone encounters in United States EDs. Opioid use decreased significantly (annual odds ratio [OR]: 0.87, p = 0.003), and there was no significant trend in NSAID use. At discharge, male patients were more likely than females (OR: 1.93, p = 0.001) to receive opioids, and Black patients were less likely than White patients (OR: 0.34, p = 0.010) to receive opioids. Regional variation was also observed, with higher odds of discharge prescriptions in the West (OR: 3.15, p = 0.003) and Midwest (OR: 2.49, p = 0.010), compared with the Northeast. Thirty-five percent of patients received opioids that were stronger than morphine. Conclusion: These results suggest improved opioid stewardship from ED physicians in response to the national opioid epidemic. However, regional variation as well as disparities in discharge prescriptions for Black and female patients underscore opportunities for continued efforts. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin [BDC]) and their analogs (tetrahydrocurcumin [THC], tetrahydrodemethoxycurcumin [THDC], tetrahydrobisdemethoxycurcumin) in reducing inflammatory cytokines and their toxicity to primary human corneal limbal epithelial cells, these cells were cultured and exposed to these compounds. Methods: The PrestoBlue assay assessed cell viability after treatment. Anti-inflammatory effects on hyperosmotic cells were determined using real-time polymerase chain reaction and significance was gauged using one-way analysis of variance and Tukey's tests, considering p-values < 0.05 as significant. Results: Curcuminoids and their analogs, at 1, 10, and 100 µM, exhibited no effect on cell viability compared to controls. However, cyclosporin A 1:500 significantly reduced cell viability more than most curcuminoid treatments, except 100 µM curcumin and BDC. All tested curcuminoids and analogs at these concentrations significantly decreased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17 A, matrix metallopeptidase-9, and intercellular adhesion molecule-1 after 90 mM NaCl stimulation compared to untreated cells. Furthermore, proinflammatory cytokine levels from hyperosmotic cells treated with 1, 10, and 100 µM curcumin, 100 µM BDC, 100 µM THC, 1 and 100 µM THDC mirrored those treated with cyclosporin A 1:500. Conclusion: The anti-inflammatory efficiency of 1 and 10 µM curcumin, 100 µM THC, 1 and 100 µM THDC was comparable to that of cyclosporin A 1:500 while maintaining cell viability. [ABSTRACT FROM AUTHOR]

Baicalin has been acknowledged for its anti-inflammatory properties. However, its potential impact on osteoarthritis (OA) has not yet been explored. Therefore, our study aimed to examine the effects of Baicalin on OA, both in laboratory and animal models. To evaluate its efficacy, human chondrocytes affected by OA were treated with interleukin-1β and/or Baicalin. The effects were then assessed through viability tests using the cell counting kit-8 (CCK-8) method and flow cytometry. In addition, we analyzed the expressions of various factors such as FOXO1, autophagy, apoptosis, and cartilage synthesis and breakdown to corroborate the effects of Baicalin. We also assessed the severity of OA through analysis of tissue samples. Our findings demonstrate that Baicalin effectively suppresses inflammatory cytokines and MMP-13 levels caused by collagenase-induced osteoarthritis, while simultaneously preserving the levels of Aggrecan and Col2. Furthermore, Baicalin has been shown to enhance autophagy. Through the use of FOXO1 inhibitors, lentivirus-mediated knockdown, and chromatin immunoprecipitation, we verified that Baicalin exerts its protective effects by activating FOXO1, which binds to the Beclin-1 promoter, thereby promoting autophagy. In conclusion, our results show that Baicalin has potential as a therapeutic agent for treating OA (Clinical Trial Registration number: 2023-61). [ABSTRACT FROM AUTHOR]

Simple Summary: Image-guided stereotactic body radiation therapy (SBRT), utilizing biocompatible superparamagnetic iron oxide nanoparticles (SPION), like ferumoxytol, has emerged as a non-invasive, safe, and effective therapy for liver tumors. However, the radiomodulating properties of ferumoxytol on hepatic macrophages have never been directly investigated. We showed that ferumoxytol affected human monocytes increasing their resistance to radiation-induced cell death. These findings provide the basis for mechanism-based optimization of SPION-enhanced image-guided functional treatment planning platform for reducing hepatotoxicity in patients with advanced hepatic cirrhosis undergoing liver SBRT for liver cancer before liver transplant. Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant. [ABSTRACT FROM AUTHOR]

Objective: Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real‐world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first‐line tumor necrosis factor inhibitor (TNFi). Methods: Data from adult patients with RA initiating a first‐line TNFi were collected from the American Rheumatology Network (January 2014–August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. Results: Among TNFi initiators (n = 15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n = 1,651), 52% discontinued their initial TNFi during follow‐up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non‐TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. Conclusion: In clinical practice, over half of patients with RA initiating a first‐line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA. [ABSTRACT FROM AUTHOR]

Purpose: To determine current prescribing patterns for topical or intraocular/periocular anti-inflammatory medications (AIMs) after routine cataract surgery. Setting: kera-net online members. Design: Cross-sectional survey. Methods: An online survey was distributed to subscribers of kera-net, a global online platform sponsored by the Cornea Society. Questions were asked regarding the use of topical or intraocular/periocular AIM after cataract surgery and types of medications prescribed. Results: Of 217 surgeon respondents (23% response rate), 171 (79%) practiced in the United States and 171 (79%) were cornea subspecialists. Most of the respondents (n = 196, 97%) prescribed topical corticosteroids after routine cataract surgery. The most frequently prescribed were prednisolone acetate (n = 162, 83%), followed by dexamethasone (n = 26, 13%), difluprednate (n = 24, 12%), and loteprednol etabonate (n = 13, 7%). Corticosteroids comprised (n = 40, 32%) of total intraocular/periocular injections, with triamcinolone acetonide 10 or 40 mg (n = 19, 47.5%) most commonly used. 23 surgeons (58%) who utilized intraocular/periocular corticosteroids also prescribed topical corticosteroids. Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 148 surgeons (73%). Conclusions: Most surgeons prescribed topical AIM after routine cataract surgery. Many surgeons injected intraocular or periocular AIM while prescribing topical AIM. The diversity of practice patterns may reflect the lack of clear evidence-based guidelines. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases. [ABSTRACT FROM AUTHOR]

The opioid epidemic in the United States has led to an increasing number of pregnant patients with opioid use disorder (OUD) presenting to obstetric units. Caring for this complex patient population requires an interdisciplinary approach involving obstetricians, anesthesiologists, addiction medicine physicians, psychiatrists, and social workers. The management of acute pain in the parturient with OUD can be challenging due to several factors, including respiratory depression, opioid tolerance, and opioid-induced hyperalgesia. Patients with a history of OUD can present in one of three categories: 1) those with untreated OUD; 2) those who are currently abstinent from opioids; 3) those being treated with medications to prevent withdrawal. A patient-centered, multimodal approach is essential for optimal peripartum pain relief and prevention of adverse maternal and neonatal outcomes. Medications for opioid use disorder (MOUD), previously referred to as medication-assisted therapy (MAT), include opioids like methadone, buprenorphine, and naltrexone. These are prescribed for pregnant patients with OUD, but appropriate dosing and administration of these medications are critical to avoid withdrawal in the mother. Non-opioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in a stepwise approach, and regional techniques like neuraxial anesthesia and truncal blocks offer opioid-sparing options. Other medications like ketamine, clonidine, dexmedetomidine, nitrous oxide, and gabapentinoids show promise for pain management but require further research. Overall, a comprehensive pain management strategy is essential to ensure the well-being of both the mother and the fetus in pregnant patients with OUD. [ABSTRACT FROM AUTHOR]

Caustic paste disbudding is increasing in popularity on commercial dairy farms in the United States, but little research has explored the pain and welfare implications beyond the acute period of this procedure. In contrast, researchers have reported it takes 7 to 9 wk, on average, for hot-iron disbudding wounds to re-epithelialize in dairy calves. Our objective was to describe wound healing and sensitivity following caustic paste disbudding. Jersey and Holstein female calves were disbudded using caustic paste (H. W. Naylor Company Inc.) at 3 d of age (n = 18), and control calves received a sham procedure (n = 15). Before disbudding, calves received a local block and a nonsteroidal anti-inflammatory drug. Calves ≥34 kg and <34 kg at birth had 0.3 or 0.25 mL of paste applied per unshaved horn bud, respectively. Following disbudding, wounds were scored 2×/wk for the presence or absence of 8 tissue categories, including the final stages: new epithelium and fully healed. Control calves were removed from the experiment after 6 wk to be hot-iron disbudded. Mechanical nociceptive threshold (MNT) measures were collected weekly to evaluate wound sensitivity until calves were removed from the study or healed. Wounds were slow to re-epithelialize (16.2 ± 5.7 wk, mean ± SD; range: 6.2–32.5 wk) and contract to be considered fully healed (18.8 ± 6 wk, mean ± SD; range: 8.7–34.1 wk). Compared with non-disbudded controls, paste calves exhibited lower MNT values for all 6 wk (mean ± SE; control: 1.46 ± 0.16; paste: 1.18 ± 0.12 N). These data indicate that wounds from caustic paste disbudding are more sensitive than undamaged tissue for at least 6 wk and take twice as long to heal compared with cautery methods described in the literature. In conclusion, caustic paste disbudding wounds took 18.8 wk to fully heal and were more sensitive than intact horn buds for 6 wk. Future work should examine whether aspects of paste application (e.g., amount used, time rubbed in, calf age, pain mitigation) could improve healing time and sensitivity. [ABSTRACT FROM AUTHOR]

Objective: Real‐world studies assessing treatment response by psoriatic arthritis (PsA) domains are limited. This study aimed to describe the patient characteristics, frequency and combinations of disease domains, disease activity, and patient‐reported outcomes (PROs) by PsA domains in patients who initiated treatment with a tumor necrosis factor inhibitor (TNFi) or interleukin‐17 inhibitor (IL‐17i). Methods: Adults with PsA who initiated treatment with a TNFi or an IL‐17i between January 2013 and January 2021 and had a 6 (±3)–month follow‐up were included. The prevalence of PsA domains, the most common domain combinations, treatment persistence, and unadjusted change in disease activity and PROs from baseline to 6 months for each PsA domain were summarized descriptively. Results: Of the 1005 eligible patients, 63% were receiving TNFi and 37% were receiving IL‐17i. Forty percent of TNFi and 14% of IL‐17i initiators received these treatments as first‐line therapy. Peripheral arthritis and skin disease were the most common PsA domains identified in 86% and 82% of patients, respectively, and the triad of peripheral arthritis, skin disease, and nail psoriasis was the most common domain combination observed in 14% of patients. More than two thirds (68%) of patients remained on therapy at 6 months' follow‐up. Improvements in disease activity and PROs were observed across all PsA domains in those receiving TNFi or IL‐17i. Conclusion: This real‐world analysis highlights the heterogeneity in domain presentation; therefore, assessing all PsA domains is important for optimal disease management. Improvements in outcomes across all PsA domains demonstrate the effectiveness of TNFi and IL‐17i in diverse patient groups exhibiting different phenotypes of PsA. [ABSTRACT FROM AUTHOR]

Fill levels, drop counts, price per drop, price per mL, and expulsion force requirements varied significantly among branded vs generic formulations of commonly prescribed ophthalmic NSAIDs. Some NSAIDs may cover the postoperative course for 2 eyes. Purpose: To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States. Setting: Tertiary care academic medical center. Design: Prospective laboratory investigation. Methods: 8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method. Results: 2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs. Conclusions: Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively. [ABSTRACT FROM AUTHOR]

To better document anesthetic and analgesic protocols used by veterinarians in general practice within the United States (US) when performing elective ovariohysterectomy in cats. Cross-sectional survey. Veterinary practitioners in the US who are members of the Veterinary Information Network Inc. (VIN). An online anonymous survey was distributed to VIN members. The survey included questions pertaining to preanesthetic evaluation, premedication, induction, monitoring and maintenance protocols, and postoperative analgesia and sedation protocols when performing ovariohysterectomy in cats. A total of 1324 veterinarians completed the survey. Respondents (number; %) reported performing preanesthetic laboratory tests [packed cell volume (256; 19.3%), complete blood cell count (893; 67.4%) and biochemistry panels (1101; 83.2%)] and preanesthetic examinations (1186; 89.6%) on the morning of surgery. The most frequently administered drugs for premedication were dexmedetomidine (353; 26.7%) and buprenorphine (424; 32.0%). The most frequently administered induction agent was propofol (451; 61.3%), and isoflurane (668; 50.4%) was the most common agent for maintenance of anesthesia. The majority of respondents reported placing intravenous catheters (885; 66.8%), administering crystalloid fluids (689; 52.0%) and providing heat support (1142; 86.3%). Participants reported using perioperative and postoperative analgesia including opioids (791; 59.7%), non-steroidal anti-inflammatory drugs (NSAIDs; 697; 52.6%) and NSAIDs dispensed for home use (665; 50.2%). Cats were commonly released home on the day of surgery (1150; 86.9%), and most participants reported contacting owners for follow-up within 1–2 days (989; 74.7%). Anesthetic protocols and management techniques for routine feline ovariohysterectomy differ widely among US veterinarians who are VIN members, and results from this study may be of use to evaluate anesthetic practices from this population of veterinarians. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer‐related deaths in the United States. Patients with the genetic disorder Familial Adenomatous Polyposis (FAP) develop hundreds to thousands of polyps that unless removed by prophylactic colectomy will progress to CRC at an early age. Nonsteroidal anti‐inflammatory drugs (NSAIDs) and the ω‐3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA), have been evaluated for their chemopreventive potential in delaying CRC onset in high‐risk patients. In our study, we determined whether the NSAID, naproxen, alone or in combination with a chemically‐stable EPA analog (TP‐252), affects tumor formation in the ApcPirc rat model. When compared to control diet, animals fed naproxen or HD TP‐252 had 66% and 82% fewer tumors, respectively. However, animals fed a combination of naproxen and HD TP‐252, exhibited a 95% reduction in tumor formation and a 98% reduction in tumor volume, respectively. To elucidate potential mechanisms of tumor protection, a comprehensive, targeted lipidomic analysis was performed on colonic mucosa to determine changes in eicosanoid metabolism. Animals receiving TP‐252 alone or in combination with naproxen had significantly reduced mucosal levels of proinflammatory ω‐6 eicosanoids (PGE2, 5‐HETE and 14,15‐DiHETrE), along with a simultaneous increase in anti‐inflammatory EPA‐derived ω‐3 eicosanoids. A comprehensive lipidomic analysis also uncovered several potential pharmacodynamic (PD) lipid biomarkers, including resolvin E2, 9‐HEPE, 12‐HEPE and 18‐HEPE, that were significantly correlated with tumor protection. Further studies with this drug combination should be focused on dose optimization and the role of EPA‐derived lipid mediators in CRC initiation and progression. [ABSTRACT FROM AUTHOR]

A redesign of consumer cost sharing in the United States is important to accelerate the adoption of biosimilars and price reductions for biologies. This article analyzes therapeutic reference pricing for anti-inflammatory biosimilars in Germany and its implications for the United States. The German experience demonstrates that a redesign of consumer cost sharing can achieve savings for payers without creating onerous financial barriers for patients. In contrast, the dominant coinsurance structure of cost sharing in the US creates strong incentives for patients to abandon treatment, especially for serious illnesses treated by complex biologies, and only weak incentives to compare prices among therapeutically equivalent products. The Medicare Payment Advisory Commission (MedPAC) has advocated that the Centers for Medicare and Medicaid Services adopt a variant of reference prices for biologies, their related biosimilars, and therapeutically similar branded alternatives by assigning them the same billing code or by paying a similar rate for all the products. The German experience demonstrates that the proposed MedPAC approach is technically feasible and would generate savings for payers without imposing access obstacles on patients. [ABSTRACT FROM AUTHOR]

To acquire information about anesthesia and analgesia protocols used by United States (US) veterinarians in primary care practices when performing routine ovariohysterectomy in dogs. Cross-sectional survey. Primary care veterinarians in the US. An online anonymous survey, originally created in New Zealand, was modified with permission and made available to Veterinary Information Network (VIN) members. The survey asked questions about performing ovariohysterectomy in healthy adolescent dogs in the categories of preanesthetic evaluation, premedication and induction protocols, maintenance protocols and monitoring equipment, and postoperative analgesic and sedation protocols and pain assessments. A total of 1213 US veterinarians completed the survey. Respondents (n ; %) reported performing preoperative laboratory tests [packed cell volume (135; 11%), complete blood cell count (889; 73%) and biochemistry panels (1057; 87%)] and preanesthetic examinations on the morning of surgery (1083; 90%). The most commonly administered drugs for premedication were acepromazine (512; 42%), hydromorphone (475; 39%) or butorphanol (463; 38%), with propofol (637; 67%) for induction of anesthesia and isoflurane (882; 73%) for maintenance of anesthesia. Most veterinarians reported placing intravenous catheters (945; 78%), administering electrolyte solutions (747; 67%) and providing heat support (1160; 96%). Perioperative and postoperative analgesia included local anesthetics (545; 45%), opioids (844; 70%) and non-steroidal anti-inflammatory drugs (NSAIDs) (953; 79%); NSAIDs were dispensed for home use (985; 81%). Dogs were most frequently discharged on the day of surgery (1068; 88%) and the owners were contacted (914; 75%) for follow-up within 1–2 days. Anesthetic management for routine ovariohysterectomy in dogs varies among US veterinary VIN members. Information from this study is useful for all veterinarians for comparison with their practice management and for teachers of veterinary anesthesia to continue to emphasize options for analgesia. [ABSTRACT FROM AUTHOR]

Objective: To examine the prevalence of side effects with methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Methods: This retrospective analysis, conducted between January 2000 and January 2019, used data from the FORWARD databank. Adult patients enrolled in the registry with self‐reported and physician‐confirmed diagnosis of PsA or RA were included if they had completed at least one questionnaire before initiating and within 12 months following initiation of MTX or a TNFi. The primary outcome was to examine the prevalence of side effects with MTX and TNFi within the year following treatment initiation. Multivariate logistic regression analysis was performed to examine the association between PsA and RA and the reporting of their side effects. Results: Overall, 116 patients with PsA and 4247 patients with RA newly initiated MTX, and 124 patients with PsA and 4361 patients with RA newly initiated a TNFi. Patients with PsA were more likely to report MTX‐related side effects than those with RA (44.8% vs. 29.4%), whereas similar proportions of patients with PsA and RA reported TNFi‐related side effects within the first year (24.2% and 22.8%, respectively). Additionally, patients with PsA initiating MTX were more likely to report nausea, vomiting, abdominal pain, depression, and tinnitus than patients with RA initiating MTX or those with PsA or RA initiating a TNFi. Conclusion: Patients with PsA reported more side effects than patients with RA, and this difference was more pronounced in those receiving MTX versus TNFi. [ABSTRACT FROM AUTHOR]

The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as a2 agonists, ß-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD. [ABSTRACT FROM AUTHOR]

Background People with cystic fibrosis (CF) routinely suffer from recurrent sinopulmonary infections. Such infections require frequent courses of antimicrobials and often involve multidrug-resistant organisms. The goal of this study was to identify real-world evidence for the effectiveness of elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) in decreasing infection-related visits and antimicrobial use in people with CF. Methods Using IBM MarketScan data, we identified 389 enrollees with CF who began taking ELX/TEZ/IVA before 1 December 2019 and were enrolled from 1 July 2019 to 14 March 2020. We also identified a comparison population who did not begin ELX/TEZ/IVA during the study period. We compared the following outcomes in the 15 weeks before and after medication initiation: total healthcare visits, inpatient visits, infection-related visits, and antimicrobial prescriptions. We analyzed outcomes using both a case-crossover analysis and a difference-in-differences analysis, to control for underlying trends. Results For the case-crossover analysis, ELX/TEZ/IVA initiation was associated with the following changes over a 15-week period: change in overall healthcare visit dates, −2.5 (95% confidence interval, −3.31 to −1.7); change in inpatient admissions, −0.16 (−.22 to −.10); change in infection-related visit dates, −0.62 (−.93 to −.31); and change in antibiotic prescriptions, −0.78 (−1.03 to −.54). Results from the difference-in-differences approach were similar. Conclusions We show a rapid reduction in infection-related visits and antimicrobial use among people with CF after starting a therapy that was not explicitly designed to treat infections. Currently, there are >30 000 people living with CF in the United States alone. Given that this therapy is effective for approximately 90% of people with CF, the impact on respiratory infections and antimicrobial use may be substantial. [ABSTRACT FROM AUTHOR]

Head injury results in thousands of hospitalizations and deaths for Americans each year, yet there are no current dietary recommendations for improving outcomes after head injury. We assessed the dietary nutrient intakes in the population with self-reported head injury with loss of consciousness (HIC) using National Health and Nutrition Examination Survey (NHANES) data. Secondary data analysis was performed on participants aged 40 years and over from the NHANES 2011-2014 surveys with and without head injury with loss of consciousness. The nutritional differences were measured between the HIC group and those who reported no head injury with loss of consciousness (No-HIC) based on average daily intakes of individual nutrients. We hypothesized that there would be dietary nutrient intake differences between the HIC and No-HIC groups. SPSS software was used to perform t tests comparing nutrient intakes of the HIC to No-HIC groups. The HIC group reported higher intakes of calories as well as carbohydrates, sugar, fat, and various vitamins and minerals compared with those in the No-HIC group. After adjusting for energy intakes, the intakes of sugar, riboflavin, alcohol, caffeine, and saturated fatty acids were higher in HIC group compared with the No-HIC group, and intakes of protein, fiber, thiamin, beta-carotene, selenium, eicosapentaenoic acid, and docosahexaenoic acid were lower in the HIC group compared with the No-HIC group. The HIC group currently is consuming a pro-inflammatory diet. Therefore, nutrition guidelines are essential to educate the head injury population to improve future health outcomes after injury. Dietary nutrient records were analyzed for 7399 National Health and Nutrition Examination Survey participants who responded to the question "Have you experienced head injury with loss of consciousness?" Dietary antioxidant intake improves outcomes by decreasing neuroinflammation and countering free radical oxidation after injury, reducing secondary injury. This study closely observed the antioxidant and anti-inflammatory nutrient intakes in participants with head injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Although a majority of patients in the U.S. receive post-acute care in skilled nursing facilities (SNFs) following hip fracture, large-sample observational studies of analgesic prescribing and use in SNFs have not been possible due to limitations in available data sources. We conducted a proof-of-concept federated analysis of electronic health records (EHRs) from 11 SNF chains to describe analgesic use during hip fracture post-acute care., Methods: We included residents with a diagnosis of hip fracture between January 1, 2018 and June 30, 2021 who had at least one administration of an analgesic. Use of analgesics was ascertained from EHR medication orders and medication administration records. We quantified the proportion of residents receiving analgesic regimens based on the medications that were administered up to 100 days after hip fracture diagnosis. Plots visualizing trends in analgesic use were stratified by multiple resident characteristics including age and Alzheimer's Disease and Related Dementias (ADRD) diagnosis., Results: The study included 23,706 residents (mean age 80.5 years, 68.6% female, 87.7% White). Most (~ 60%) residents received opioids + APAP. Monotherapy with APAP or opioids was also common. The most prevalent regimens were oxycodone + APAP (20.1%), hydrocodone + APAP (15.8%), APAP only (15.1%), tramadol + APAP (10.4%), and oxycodone only (4.3%). During the study period, use of APAP-only increased, opioids-only decreased, and opioids + APAP remained stable. Use of APAP-only appeared to be more prevalent among individuals aged > 75 years (versus ≤ 75 years) and those with ADRD (versus without)., Conclusions: We successfully leveraged federated SNF EHR data to describe analgesic use among residents receiving hip fracture post-acute care., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are among the most-frequently used medications. Although these medications have different mechanisms of action, they have similar indications and treatment duration has been positively correlated with cardiovascular risk although the degree of risk varies by medication. Our objective was to study treatment effects of chronic use of individual NSAID medications and acetaminophen on all-cause mortality among patients who tested positive for COVID-19 while accounting for adherence. We used the VA national datasets in this retrospective cohort study to differentiate between sporadic and chronic medication use: sporadic users filled an NSAID within the last year, but not recently or regularly. Using established and possible risk factors for severe COVID-19, we used propensity scores analysis to adjust for differences in baseline characteristics between treatment groups. Then, we used multivariate logistic regression incorporating inverse propensity score weighting to assess mortality. The cohort consisted of 28,856 patients. Chronic use of aspirin, ibuprofen, naproxen, meloxicam, celecoxib, diclofenac or acetaminophen was not associated with significant differences in mortality at 30 days (OR = 0.98, 95% CI: 0.95–1.00; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.00, 95% CI: 0.99–1.02, respectively) nor at 60 days (OR = 0.97, 95% CI: 0.95–1.00; OR = 1.00, 95% CI: 0.99–1.01; OR = 0.99, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.00; OR = 0.99, 95% CI: 0.97–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.01, 95% CI: 0.99–1.02, respectively). Although the study design cannot determine causality, the study should assure patients as it finds no association between mortality and chronic use of these medications compared with sporadic NSAID use among those infected with COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosis difficulties are common for ankylosing spondylitis (AS) patients, leading to inadequate and inconsistent treatment. We evaluated the national and geographic variability in disease diagnosis and treatment in the United States. Methods: This retrospective, cross-sectional analysis utilized the IBM® MarketScan® Administrative Claims Database from 2014 to 2019. AS patients ≥ 18 years of age with continuous medical and pharmacy enrollment during the calendar year and complete geographic information during the study period were included. Patient cohorts assessed were D1 (≥ 1 AS diagnoses within each calendar year of assessment between 2014 and 2019), D2 (≥ 2 non-rheumatologist AS diagnoses), and D3 (≥ 2 rheumatologist AS diagnoses). For D2 and D3, diagnoses were ≥ 6 months apart, but within 18 months. Annual AS diagnostic prevalence and treatment rates were determined from 2014 to 2019 nationally and per state in 2019. Treatments assessed were disease-modifying antirheumatic drugs (DMARDs), opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and methotrexate. Results: Nationally, AS diagnostic prevalence increased from 2014 to 2019, with 2019 rates of 9.6 (D1), 5.1 (D2), and 3.5 (D3) per 10,000 persons. Diagnostic prevalence varied between states, which was not explained by age, sex, racial distribution, or rheumatologists per capita. Nationally, a greater percentage of D3 patients vs. D1 and D2 patients received biologic/targeted synthetic DMARDs (bDMARD/tsDMARDs) and conventional synthetic DMARD. Opioid use ranged from 37 to 40% in 2019 and decreased from 2014 for all cohorts. Corticosteroid and methotrexate use decreased slightly, while NSAID and bDMARD/tsDMARD use generally increased from 2014 to 2019. Conclusions: AS diagnostic prevalence is increasing nationally, though it remains low among some states. bDMARD/tsDMARDs use was more common among patients treated by rheumatologists. Opioid and corticosteroid use is decreasing, though national rates remain high with significant state variability. Further education is needed, particularly in states with low prevalence and inadequate treatment, to improve diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objective: The SARS-CoV-2 pandemic has had a profound effect on the healthcare system. This study aimed to identify its effects on sports medicine physicians during the early phase of this pandemic. Design: Survey study. Setting: Sports medicine providers. Participants: Physician members of the American Medical Society for Sports Medicine were surveyed between March 25 and April 4, 2020. A total of 810 responses were obtained from 2437 physicians who viewed the survey. Interventions: The survey consisted of questions examining demographics, prepandemic practice patterns, anxiety and depression screening, and new beliefs and behaviors following government-based medical policy changes resulting from the pandemic. Main Outcome Measures: Changes in clinical volume and treatment practices, Patient Health Questionnaire (PHQ-4). Results: The mean in-person clinic visits reduced to 17.9%, telephone visits to 24.4%, telemedicine (video) visits to 21.8%, and procedural visits to 13.8% of prepandemic practice volume. The mean PHQ-4 scores for physicians were 2.38 ± 2.40. Clinic and procedural volumes were reduced less by male physicians, as well as more experienced physicians, nonphysical medicine and rehabilitation training background, in government or private practice, and in the Southern region of the United States (P < 0.05). Physicians were more likely to reduce their anti-inflammatory (37.8% decreasing vs 6.8% increasing, P < 0.001) and opioid (10.5% vs 6.8%, P = 0.003) prescriptions rather than increase. Conclusions: During the early phase of the SARS-COV-2 pandemic sports medicine physicians reported reducing in-person evaluation, management, and procedure volume by over 80%. Multiple demographic and geographic factors were associated with practice volume changes. [ABSTRACT FROM AUTHOR]

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to describe the use of complementary and alternative medicine (CAM), pain reliever use and the expectations refugees have of physicians about their practice of CAM use in the USA. Individuals with a refugee background are one of the populations who use CAM for treatment. However, to date, there is insufficient empirical evidence to describe CAM use among refugees resettled in the USA. In addition, collecting information about the use of pain relievers would help better understand the experiences of individuals with a refugee background. Design/methodology/approach: Data was collected from August 2018 to November 2019 using a self- or interviewer-administered survey from 94 refugees 18 years of age or older who had settled in the USA. Findings: This study found the following: CAM practice is very common among refugees resettled in the USA, most refugees use non-prescription pain medicine and refugees prefer to see physicians who understand CAM. This study contributes valuable findings in the usage of CAM among refugees and determines that CAM is commonly used among refugees resettled in the USA for pain management. Originality/value: By better understanding CAM, physicians can address a direct need for the refugee population-seeking health care in the USA and other countries that host refugee resettlement. [ABSTRACT FROM AUTHOR]

Tirbanibulin (Klisyri®) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global partners for the topical treatment of actinic keratosis, and psoriasis. Based on the data from two pivotal phase III trials the drug was recently approved for marketing in the US as a topical treatment for actinic keratosis. This article summarizes the milestones in the development of tirbanibulin leading to this first approval. [ABSTRACT FROM AUTHOR]

Objectives We sought to evaluate perceptions of biosimilar products among US rheumatologists who prescribe TNF-α inhibitors, given that 10 TNF-α inhibitor biosimilars and two rituximab biosimilars have Food and Drug Administration (FDA) approval. Methods A 19-question self-administered online survey was conducted from 6 May to 1 June 2019, and fielded by WebMD, LLC. Rheumatologists (n  = 9050) who were members of Medscape.com and its partner panels were invited to participate. Likert and other rating scales were used to collect responses, which were summarized descriptively. Results Responses were obtained from 320 board-certified US rheumatologists, 85% of whom were fellows of the ACR. Nearly all respondents were familiar with the FDA definition of a biosimilar product and were aware that an infliximab biosimilar was FDA approved; fewer realized that adalimumab, etanercept and rituximab biosimilars were also FDA approved. Most respondents (84%) were aware that an approved biosimilar was not automatically deemed interchangeable by the FDA. Rheumatologists were more likely to initiate biosimilar treatment for a biologic treatment-naïve patient with RA (73%) than they were to switch to the biosimilar for a patient with RA doing well on the reference product (35%). Conclusions The results of this survey suggest that US rheumatologists have a good understanding and acceptance of biosimilar products, particularly for the initiation of treatment in biologic-naïve individuals. They were hesitant to switch from a reference product to a biosimilar for a patient doing well on the reference product. Additional education on biosimilars is required to help inform treatment decisions by rheumatologists. A plain language summary of this article has been uploaded as supplementary material, available at Rheumatology online. [ABSTRACT FROM AUTHOR]

We report utilization patterns and characteristics of patients treated with biologic anti-inflammatory agents in a large commercially insured patient population in the United States. We identified adult (age ≥18 years) patients receiving biologic antiinflammatory agents between 1 January 2012 and 31 March 2019 across the five Research Partners in the Biologic and Biosimilars Collective Intelligence Consortium's Distributed Research Network. We examined the number of incident use episodes for each biologic, as well as patient demographic and clinical characteristics. Curated data and analytic tools from the Food and Drug Administration's Sentinel System were used to perform the analyses. We identified 90,360 incident episodes of tumor necrosis factor-alpha inhibitors (TNFi) and 70,506 incident episodes of non-TNFi medications. Adalimumab was the most common TNFi drug (47% of all TNFi episodes) and showed a steady increase in utilization during the study period compared to other TNFi agents. Rituximab was the most commonly initiated non-TNFi medication (44% of non-TNFi episodes). Other non-TNFi agents, namely, ustekinumab, vedolizumab, and secukinumab, demonstrated notable increases in utilization over time. Biosimilar use was limited; we observed 653 incident episodes for infliximab-dyyb and 39 incident episodes for infliximab-abda. As more biologics enter the market, greater variation in the use of biologics with similar indications and between biologic originators and biosimilars is anticipated. Because information on efficacy and safety at the time of drug approval is limited, post-marketing surveillance and research is needed to monitor medication safety and evaluate effectiveness between biologic drugs using real-world data. [ABSTRACT FROM AUTHOR]

Aim: Inflammatory bowel disease (IBD), a traditionally "western disease", has recently been reported to have risen in incidence in China. We summarize differences between Chinese and Western IBD based on relevant literatures published in both Chinese and English. Subject and methods: Relevant references published in English were collected from an electronic database via PubMed and relevant references published in Chinese were also collected. Results: Emerging clinical epidemiological data have shown a striking rise in the incidence rate of IBD in Mainland China over the last two decades. Although the current incidence rate of IBD in Mainland China is still lower than that in Western countries, the associated disease burden might be much heavier than previously thought due to the huge population. Clinical data have shown that disease characteristics (e.g., age of onset, male/female ratio, and location and disease severity) of Chinese IBD patients are different to those of Western IBD patients. Unlike the widely used bioimmunotherapeutic agents in Western countries, the management of IBD in China relies predominately on aminosalicylates and corticosteroids. The use of bioimmunotherapeutic agents is limited to a small number of IBD patients in China. Currently, many challenges remain, including the lack of properly trained IBD specialists, poor information availability to support patient self-management, and inappropriate treatment of some patients. Conclusion: Based on the current findings, the disease burden, characteristics, and treatment of Chinese IBD patients are slightly different to those of Western IBD patients. There are still great improvement requirements for the clinical management of IBD in China. [ABSTRACT FROM AUTHOR]

Pinterest, a widely used social media platform, has shaped how people seek and share health information. Cannabidiol (CBD), a non-psychoactive component of cannabis is marketed as a treatment for many conditions and sales rose to more than 820 million in 2017. Yet CBD is mostly unregulated, legality is murky, and many of the health claims are not scientifically proven. Purpose: This content analysis examined how CBD products were portrayed on Pinterest. Methods: In 2018, using the search terms cannabidiol and CBD, researchers sampled every fifth pin to collect 226 relevant pins. A codebook was developed, pilot tested, and used to code pins. Results: The majority (91.6%) of pins positively portrayed CBD with many claiming a physical or mental benefit including anxiety, depression, pain, and inflammation relief. Most pins did not (98.2%) address potential side effects or recommend dosage. In this sample, user engagement was high with 85.2% of pins being saved and links to commercial sites selling CBD products, personal blogs, and social media accounts. Conclusions: Social media has become a powerful source of health information. This study revealed widespread acceptance of the use of CBD products with minimal information from reliable public health sources represented. [ABSTRACT FROM AUTHOR]

Objectives: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States.Design: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings.Setting: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock).Patients: Adults greater than or equal to 18 years old with septic shock.Interventions: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 μg tablet once daily).Measurements and Main Results: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient.Conclusions: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. [ABSTRACT FROM AUTHOR]

Introduction: The Food and Drug Administration (FDA) approved certolizumab-pegol, the first biologic for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA), for use in the United States (US) in March of 2019. The objective of this study was to investigate biologic use and reasons for switching therapy among patients with nr-axSpA in the US. Methods: This was a real-world, cross-sectional study of rheumatologists conducted in the US. Data were collected from June to August of 2018 via rheumatologist-completed patient record forms. Data from patients who had a rheumatologist-confirmed diagnosis of nr-axSpA were included in the study. Rheumatologists provided information on current medication use and reasons for switching biologics. Results: Eighty-eight rheumatologists collected data on 495 nr-axSpA patients. Over half of nr-axSpA patients were male (53.3%), with a mean age of 44.2 years, and 69.8% of patients reported working full-time. Of the 495 nr-axSpA patients, 48.1% were receiving a biologic and no conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), 18.4% csDMARD (no biologic), 18.2% non-steroidal anti-inflammatory drug (NSAIDs)/COX-2 (no biologic or csDMARD), 11.5% a biologic and a csDMARD, 2.0% were receiving no therapy, and 1.8% other therapy (no biologic, csDMARD, or NSAID/COX-2). Of 295 patients receiving a biologic, 77.8% were receiving their first, 13.8% their second, and 8.3% their third or more biologic. Of 74 nr-axSpA patients who switched from a previous biologic to their current biologic, rheumatologists reported that 51.4% switched due to condition worsening, 48.6% had a loss of response over time, 27.0% switched due to a lack of pain alleviation, and 25.7% of patients switched because remission was not induced. Conclusions: This study suggests that around 60% of nr-axSpA patients were receiving biologic therapy prior to the approval of certolizumab pegol. Switching of biologics is frequent in nr-axSpA patients and is usually due to lack of efficacy, loss or response, and effort to accomplish remission. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), degeneration of cartilage associated with aging, lifestyle, and trauma, is one of the most common diseases that leads to lower quality of life and socioeconomic burden in the United States. Clinically, OA is initially managed by non-steroidal anti-inflammatory drugs, but eventually requires surgical intervention to reduce pain and increase function. Cartilage is a mechanotransductive tissue and requires a mechanical stimulus to sustain its mechanical and physiologic properties. Low-intensity pulsed ultrasound (LIPUS) is a cyclic acoustic wave that can provide essential mechanical stimuli to activate molecular and cellular pathways leading to chondrocyte proliferation, differentiation and activity, as well as to inhibit inflammatory pathways associated with OA. The activation of chondrocyte proliferation and inhibition of anti-inflammatory cytokines make LIPUS a potential therapy for mild to moderate OA. Although a few review articles have described the effects of ultrasound on chondrocytes and cartilage, there remains a need for a comprehensive analysis of our current understanding of the basic science and clinical status of the effects of low-intensity ultrasound on chondrocytes and cartilage and the implications of these studies on LIPUS as a therapeutic option for OA. This review analyzes recent literature describing the results of LIPUS using in vitro and in vivo pre-clinical models and clinical studies, as well as future directions for research. [ABSTRACT FROM AUTHOR]

The association of prescription NSAIDs to presence of depression among adults with inflammatory chronic conditions in adults with and without depression and seeking care in routine clinical practice remains unknown. We examined the association of prescription NSAIDs to depression among adults with inflammatory chronic conditions in a nationally representative sample of the US non-institutionalized civilian population. We used a retrospective cross-sectional design. Data on 10,713 adults with inflammatory chronic conditions were derived from 2015 Medical Expenditure Panel Survey (MEPS). The dependent variable was the presence or absence of depression and the key independent variable was prescription NSAIDs use. Logistic regression models were used to examine the adjusted associations of prescription NSAIDs to depression. In these regressions, other independent variables (biological, sociocultural, socio-economic, access to healthcare services, medical conditions and treatment factors, behavioural, and environmental factors) that may affect the relationship of prescription NSAIDs to depression were also included. All analyses accounted for the complex survey design of MEPS. Overall, 18.2% reported depression. Almost 21% used prescription NSAIDs. In the unadjusted model, prescription NSAIDs use had higher odds of depression (OR = 1.59;95%CI = [1.40, 1.82]) as compared to those without NSAIDs. In the fully-adjusted logistic regression model, with controls for other independent variables, adults using prescription NSAIDs had no significant association with depression (AOR = 0.97;95%CI = [0.84, 1.13]) compared to those without NSAIDs. In this first real-world study of all adults (with and without depression) in the US, we did not observe a statistically significant association of prescription NSAIDs to the presence of depression. [ABSTRACT FROM AUTHOR]

Background: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery.Methods: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken.Results: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake.Conclusions: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management. [ABSTRACT FROM AUTHOR]

Lichen sclerosus (LS) is a severe, chronic, dermatosis characterised by inflammatory, sclerotic, pruritic lesions that causes significant morbidity in patients of all genders and ages. In boys, the lesions typically affect the foreskin and glans (termed balanitis xerotica obliterans (BXO)), leading to phimosis and potentially meatal stenosis. The incidence of the disease is not well reported but the average age of affected boys is 8 years (range 1-16). Diagnosis can often be made clinically, although histological study remains important to rule out important differential diagnoses. Complications include genital scarring, urinary and sexual dysfunction as well as the development of carcinomas in adult life. Circumcision has been regarded as definitive management of BXO in boys, but this may be supplemented with medical therapies such as topical steroids, immune modulators, intralesional triamcinolone and ozonated olive oil. Supportive measures including emollients, avoidance of irritants, surveillance of complications and recurrence as well as education and counselling remain important.Conclusion: BXO remains an important cause of phimosis in boys. The frequency of this condition appears unclear but seems likely to be less than 1% of males. Treatment generally involves circumcision, with some evidence that topical steroids or immunomodulators may decrease the incidence of recurrent meatal stenosis.What is Known:• Surgical circumcision is considered the definitive management of BXO• Many aspects of BXO are still in contention or require further study including the epidemiology and aetiology.What is New:• There is increasing awareness of non-surgical modalities that may be used in adjunct to surgery including topical corticosteroids, immune modulators, intralesional triamcinolone and ozonated olive oil• Awareness of meatal stenosis-related BXO has led to the development of surgical techniques such as preputioplasty as well as buccal mucosal inlay grafts. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of fusidic acid derivatives as new inflammatory drugs inhibitors were designed and synthesized. • Compared with fusidic acid, compound b2 showed significant inhibitory activity against NO, IL-6 and TNF-α with IC 50 values of 5.382, 7.767 and 7.089, respectively. • Compound b2 role in anti-inflammatory activity and alleviates acute lung injury via inhibiting MAPK/NF-κB and Bax/Bcl-2 pathway. Acute lung injury (ALI) are severe forms of diffuse lung disease that impose a substantial health burden all over the world. In the United States, approximately 190,000 cases per year of ALI each year, with an associated 74,500 deaths per year. Anti-inflammatory therapy has become a reasonable approach for the treatment of patients with ALI. In this study, fusidic acid derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 30 new fusidic acid derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW264.7 cells. Of them, b2 was found to be the most active, with a higher efficiency compared with fusidic acid and celecoxib in 10 μM. In vitro , we further measured b2 inhibited inflammatory factor NO (IC 50 = 5.382 ± 0.655 μM), IL-6 (IC 50 = 7.767 ± 0.871 μM), and TNF-α (IC 50 = 7.089 ± 0.775 μM) and b2 inhibited inflammatory cytokines COX-2 and iNOS, ROS production, NF-κB/MAPK and Bax/Bcl-2 signaling pathway pathway. In vivo, b2 attenuated ALI pathological changes and inhibited inflammatory cytokines COX-2 and iNOS in lung tissue and NF-κB/MAPK and Bax/Bcl-2 signaling pathway. In conclusion, b2 may be a promising anti-inflammatory lead compound. [ABSTRACT FROM AUTHOR]

Dentists and physicians alike often prescribe opioids for dental pain management. The purpose of this study was to identify the common practices among United States endodontists for prescribing opioids to their patients. A descriptive, cross-sectional survey was developed to query 1000 American Association of Endodontists members from all 7 districts in the United States. The 20-question survey addressed provider demographics, types and frequency of medications prescribed, and clinical scenarios that compelled prescription-writing habits. The anonymous survey was electronically mailed. There was a preference to prescribe nonsteroidal anti-inflammatory drugs and/or acetaminophen followed by hydrocodone to manage endodontic pain. The majority of respondents limited an opioid prescription to ≤4 days. Different demographics played a role in the response to direct questions if they ever felt or succumbed to pressure toward prescribing opioids. Opioids are the second most prescribed medication to manage endodontic postoperative pain. Practice background was a significant factor in feeling pressure to prescribe an opioid. [ABSTRACT FROM AUTHOR]

Introduction: We aim to assess the real-world, US patient-reported impact of ankylosing spondylitis (AS) on quality of life (QOL) across physical, discomfort, social, and emotional domains. Methods: Demographic and QOL data were collected from a random sample of patients associated with the Spondylitis Association of America (SAA) from July to December 2017. QOL measures were based on the Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL) questionnaire. The survey evaluated AS impact on the physical domain on the day of survey participation and impact on the discomfort, social, and emotional domains within the week before participation. A 3:1 (male to female) weighting was performed to reflect the reported prevalence of AS in US adults. Results: Of 820 respondents who completed the survey, 716 self-reported receiving an AS diagnosis from their doctor and were included in this analysis (mean age, 55.5 years; 46.9% male). The mean total EASi-QoL score was 28.9 (weighted); overall, 33.7%, 31.7%, and 34.7% of respondents, respectively, reported a low (EASi-QoL score 0–17), a medium (18–35), and a high (≥ 36) impact of AS on QOL. The physical domain was most impacted; 41.9% of respondents had an EASi-QoL score ≥ 10 (weighted). Women were significantly more likely than men to report a high impact of AS on all QOL domains. Biologic users reported an impact on QOL comparable with the impact on QOL of nonsteroidal anti-inflammatory drug use. AS also impacted lifestyle characteristics, including career choice and sports participation. Conclusion: AS negatively impacted all QOL domains analyzed. The incorporation of subjective measures of disease into disease evaluation should be considered. Funding: Novartis Pharmaceuticals Corporation and UCB, Inc. Plain Language Summary: Plain language summary available for this article. [ABSTRACT FROM AUTHOR]