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ID PMID Title PublicationDate abstract
35126098 Synthesis, Characterization, and in vivo Evaluation of a Novel Potent Autotaxin-Inhibitor. 2021 The autotaxin-lysophosphatidic acid (ATX-LPA) signaling pathway plays a role in a variety of autoimmune diseases, such as rheumatoid arthritis or neurodegeneration. A link to the pathogenesis of glaucoma is suggested by an overactive ATX-LPA axis in aqueous humor samples of glaucoma patients. Analysis of such samples suggests that the ATX-LPA axis contributes to the fibrogenic activity and resistance to aqueous humor outflow through the trabecular meshwork. In order to inhibit or modulate this pathway, we developed a new series of ATX-inhibitors containing novel bicyclic and spirocyclic structural motifs. A potent lead compound (IC(50) against ATX: 6 nM) with good in vivo PK, favorable in vitro property, and safety profile was generated. This compound leads to lowered LPA levels in vivo after oral administration. Hence, it was suitable for chronic oral treatment in two rodent models of glaucoma, the experimental autoimmune glaucoma (EAG) and the ischemia/reperfusion models. In the EAG model, rats were immunized with an optic nerve antigen homogenate, while controls received sodium chloride. Retinal ischemia/reperfusion (I/R) was induced by elevating the intraocular pressure (IOP) in one eye to 140 mmHg for 60 min, followed by reperfusion, while the other untreated eye served as control. Retinae and optic nerves were evaluated 28 days after EAG or 7 and 14 days after I/R induction. Oral treatment with the optimized ATX-inhibitor lead to reduced retinal ganglion cell (RGC) loss in both glaucoma models. In the optic nerve, the protective effect of ATX inhibition was less effective compared to the retina and only a trend to a weakened neurofilament distortion was detectable. Taken together, these results provide evidence that the dysregulation of the ATX-LPA axis in the aqueous humor of glaucoma patients, in addition to the postulated outflow impairment, might also contribute to RGC loss. The observation that ATX-inhibitor treatment in both glaucoma models did not result in significant IOP increases or decreases after oral treatment indicates that protection from RGC loss due to inhibition of the ATX-LPA axis is independent of an IOP lowering effect.
34907694 Analytical evaluation of the Nittobo Medical tartrate resistant acid phosphatase isoform 5 2022 Feb 23 OBJECTIVES: Tartrate-resistant acid phosphatase, isoform 5b (TRACP-5b) is a bone resorption marker not influenced by renal function or food intake. TRACP-5b can be measured with Nittobo Medical enzymatic-immunoassay and IDS-iSYS automated immunoassay. We evaluated the Nittobo assay and established reference ranges for a Western-European population. We compared Nittobo and IDS results in different well-defined clinical populations. METHODS: We established the limits of detection and quantification (LOD-LOQ), linearity, imprecision and the reference ranges in 119 males, 50 women (<45 years) and 120 women (>60 years) for TRACP-5b with the Nittobo assay. We compared both assays in 30 hemodialyzed (HD), and 40 stage 3-5 patients suffering from chronic kidney disease (CKD), 40 patients suffering from rheumatoid arthritis and osteoporosis and 80 post-menopausal women. We measured TRACP-5b, β-crosslaps (β-CTX), bone alkaline phosphatase (B-ALP) and PTH in 20 hemodialyzed (HD) and 40 CKD patients. RESULTS: LOD and LOQ were 0.02 and 0.35 U/L. CV ranged from 8.3 to 4.3% (2/5 samples presenting CV > desirable CV). Method was linear up to of 11.3 U/L. Upper and lower limits of normality were 0.8-7.6 U/L in men, 0.9-4.7 U/L in women <45 and 0.9-7.1 U/L in women >60. The regression equation between the 2 methods was Nittobo = 1.13 (95% CI: 1.09-1.16) × iSYS - 0.4 (95% CI: -0.5; -0.3). TRACP-5b and b-ALP were in their respective reference ranges for most of CKD and HD patients. That was not the case for β-CTX, which increased with decreasing eGFR. CONCLUSIONS: Nittobo TRACP-5b presents interesting analytical features and a good concordance with IDS iSYS. These methods could thus potentially be harmonized.
34730279 Recreational Physical Activity and Risk of Incident Knee Osteoarthritis: An International 2022 Apr OBJECTIVE: The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. METHODS: Data were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5-12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. RESULTS: Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93-1.12]), radiographic OA (RR 1.00 [95% CI 0.94-1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96-1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. CONCLUSION: Our findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.
35497059 Health conditions in adults with HIV compared with the general population: A population-ba 2022 May BACKGROUND: Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status. METHODS: We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression. FINDINGS: There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20-0.64]) and hypertension (OR_0.78 [0.65-0.94]); rheumatoid arthritis (OR 0.27 [0.05-0.84]); asthma (OR_0.65 (0.53-0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09-0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85-5.20]); pulmonary embolism (OR_2.06 [1.15-3.36]); male infertility (OR_2.23 [1.50-3.16]) and female infertility (OR_2.01 [1.34-2.88]); bipolar disorder (OR_2.93 [1.52-5.05]) and depression (OR_1.49 [1.28-1.71]); cervical malignancy (OR_4.64 [1.15-12.15]); and infections. INTERPRETATION: Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care. FUNDING: The project was funded by the Bart's Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme.
35486323 Methotrexate Cutaneous Ulceration: A Systematic Review of Cases. 2022 Apr 29 BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.
35457257 Identification of Novel Natural Product Inhibitors against Matrix Metalloproteinase 9 Usin 2022 Apr 18 Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases involved in multiple cellular processes. Among the MMP isoforms, MMP-9 regulates cancer invasion, rheumatoid arthritis, and osteoarthritis by degrading extracellular matrix proteins present in the tumor microenvironment and cartilage and promoting angiogenesis. Here, we identified two potent natural product inhibitors of the non-catalytic hemopexin domain of MMP-9 using a novel quantum mechanical fragment molecular orbital (FMO)-based virtual screening workflow. The workflow integrates qualitative pharmacophore modeling, quantitative binding affinity prediction, and a raw material search of natural product inhibitors with the BMDMS-NP library. In binding affinity prediction, we made a scoring function with the FMO method and applied the function to two protein targets (acetylcholinesterase and fibroblast growth factor 1 receptor) from DUD-E benchmark sets. In the two targets, the FMO method outperformed the Glide docking score and MM/PBSA methods. By applying this workflow to MMP-9, we proposed two potent natural product inhibitors (laetanine 9 and genkwanin 10) that interact with hotspot residues of the hemopexin domain of MMP-9. Laetanine 9 and genkwanin 10 bind to MMP-9 with a dissociation constant (K(D)) of 21.6 and 0.614 μM, respectively. Overall, we present laetanine 9 and genkwanin 10 for MMP-9 and demonstrate that the novel FMO-based workflow with a quantum mechanical approach is promising to discover potent natural product inhibitors of MMP-9, satisfying the pharmacophore model and good binding affinity.
35337124 Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Eva 2022 Mar 8 The symptoms of some diseases show circadian rhythms, such as the morning stiffness associated with pain at the time of awakening in rheumatoid arthritis. Therapy for such diseases doesn't require immediate release or sustained release of medicament. In such therapies, pulsatile drug release is more suitable with a programmed drug release. The purpose of this research was to formulate press-coated aceclofenac tablets for pulsatile drug delivery with a distinct delay time of no drug release and release of the drug when it is more likely desired (i.e., after 5 to 6 h). Immediate release core tablets having aceclofenac were formulated. Three formulations, F1, F2, and F3, were prepared with variable concentrations of sodium croscarmellose. Pre- and post-compression tests were performed on the core tablets. The selection criteria included the lowest disintegration time as a requirement of pulsatile drug delivery with an immediate release core and a delayed release coat. The disintegration times of F1, F2, and F3 were 120 s, 60 s, and 15 s, respectively. Therefore, the F3 formulation was selected as the core tablet formulation because it had the shortest disintegration time (15 s). The core tablets were press-coated using different polymers, such as HPMC K100M, Eudragit L100, HEC, and HPMC E5. The polymers were used in the coatings to hinder the release of the core for the desired time. 36 formulations of polymer were prepared: A1 to A10 had HPMC K100M and Avicel PH102; formulations B1 to B6 had HPMC K100M, Eudragit L100, and Avicel PH102; formulations C1 to C7 had HPMC K100M and hydroxyethyl cellulose; formulations D1 to D7 had HPMC K100M and HPMC E5; and formulations E1 to E6 had changed the coating weight of the formulation used for D6 (having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5%). Evaluations of the press-coated tablets were carried out through thickness, hardness, weight variation, friability, and in vitro dissolution tests. These parameters concluded that the formulation of E6, having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5% at 600 mg weight, was the most optimum formulation as it showed 3.5% drug release after 4 h, 21.4% drug release after 5 h, and 99.27% drug release after 6 h.
35321879 Pharmacologically Enhanced Regulatory Hematopoietic Stem Cells Revert Experimental Autoimm 2022 Apr 1 Type 1 diabetes (T1D) is characterized by the loss of immune self-tolerance, resulting in an aberrant immune responses against self-tissue. A few therapeutics have been partially successful in reverting or slowing down T1D progression in patients, and the infusion of autologous hematopoietic stem cells (HSCs) is emerging as an option to be explored. In this study, we proposed to pharmacologically enhance by ex vivo modulation with small molecules the immunoregulatory and trafficking properties of HSCs to provide a safer and more efficacious treatment option for patients with T1D and other autoimmune disorders. A high-throughput targeted RNA sequencing screening strategy was used to identify a combination of small molecules (16,16-dimethyl PGE(2) and dexamethasone), which significantly upregulate key genes involved in trafficking (e.g., CXCR4) and immunoregulation (e.g., programmed death ligand 1). The pharmacologically enhanced, ex vivo-modulated HSCs (regulatory HSCs [HSC.Regs]) have strong trafficking properties to sites of inflammation in a mouse model of T1D, reverted autoimmune diabetes in NOD mice, and delayed experimental multiple sclerosis and rheumatoid arthritis in preclinical models. Mechanistically, HSC.Regs reduced lymphocytic infiltration of pancreatic β cells and inhibited the activity of autoreactive T cells. Moreover, when tested in clinically relevant in vitro autoimmune assays, HSC.Regs abrogated the autoimmune response. Ex vivo pharmacological modulation enhances the immunoregulatory and trafficking properties of HSCs, thus generating HSC.Regs, which mitigated autoimmune diabetes and other autoimmune disorders.
35280993 Activation of LXR Nuclear Receptors Impairs the Anti-Inflammatory Gene and Functional Prof 2022 Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions but their contribution to human macrophage polarization remains unclear. The LXR pathway is enriched in pro-inflammatory macrophages from rheumatoid arthritis as well as in tumors-associated macrophages from human tumors. We now report that LXR activation inhibits the anti-inflammatory gene and functional profile of M-CSF-dependent human macrophages, and prompts the acquisition of a pro-inflammatory gene signature, with both effects being blocked by an LXR inverse agonist. Mechanistically, the LXR-stimulated macrophage polarization shift correlates with diminished expression of MAFB and MAF, which govern the macrophage anti-inflammatory profile, and with enhanced release of activin A. Indeed, LXR activation impaired macrophage polarization in response to tumor-derived ascitic fluids, as well as the expression of MAF- and MAFB-dependent genes. Our results demonstrate that LXR activation limits the anti-inflammatory human macrophage polarization and prompts the acquisition of an inflammatory transcriptional and functional profile.
35168291 The safety and clinical effectiveness of rapid infusion with CT-P10 in patients with non-H 2022 Feb 15 Rapid infusion (RI) of the rituximab biosimilar CT-P10 is currently only an approved treatment regimen for the treatment of rheumatoid arthritis. Although both CT-P10 and reference rituximab are known to be frequently administered using a RI regimen (≤90 min) in clinical practice, published data on the safety of RI of CT-P10 in patients with NHL and CLL are limited. Hence, this study collected real-world safety and effectiveness data on RI-CT-P10 from the medical records of 196 patients with NHL or CLL in 10 European centers, 6 months after the date of the first RI (index date); the infusion-related reaction (IRR) rate was compared to previously published data. Ten percent (95% confidence interval 6%-15%; n = 20/196) of patients experienced an infusion-related reaction (IRR) on day 1-2 post-index, which was not significantly different (p = 0.45) to the IRR rate for rituximab described in a previous meta-analysis (8.8%). During the observation period, 2% of patients experienced grade 3-5 IRRs and 85% (n = 166) experienced an adverse event (non-IRR). The most common reason for discontinuation of first-line CT-P10 was planned treatment completion (81%; n = 158). Complete response and partial response to CT-P10 was observed in 74% (n = 142/192) and 22% (n = 42/192) of patients, respectively. The results of this real-world study demonstrate that the safety and effectiveness profile of RI-CT-P10 is similar to RI of reference rituximab and therefore support the current use of RI-CT-P10 in patients with NHL and CLL.
35101085 MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligamen 2022 Jan 31 BACKGROUND: After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10-15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation. METHODS: We will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25-50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling. DISCUSSION: There is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572256 . Registered on October 1, 2020.
34768006 [Management of HPV-induced cervical lesions in immunosuppressed patients - Review of the 2022 Jan INTRODUCTION: Current French recommendations for the management of cervical lesions related to human papilloma virus (HPV) infection are limited to general population. Patients who are immunocompromised appear to be at increased risk of induced HPV lesions. The objective of this review is to summarize the various existing data about risk of induced HPV lesions in immunocompromised patients to specify the management. METHODS: The Medline database was searched through the Pubmed portal, as well as the recommendations of various international learned societies. RESULTS: Situations with an increased risk are regardless of treatment: Human Immunodeficiency Virus (HIV) infection, transplants, lupus. Patients with chronic inflammatory bowel disease (IBD) and rheumatoid arthritis are at increased risk only when immunosuppressive therapy is required. Screening for dysplasic intraepithelial lesions in HIV+ patients should be more sustained than in the general population. Due to lack of data, recommendations for other conditions have been extrapolated from the management of HIV+ patients. HPV vaccination is effective in these populations, particularly at times when the immune system is the most effective. DISCUSSION: Identified immunocompromised populations are at higher risk of induced HPV lesions due to an incomplete immune response and should be screened on a sustained basis. In addition, HPV vaccination should be encouraged.
35628531 IL-17A Is the Critical Cytokine for Liver and Spleen Amyloidosis in Inflammatory Skin Dise 2022 May 20 Systemic amyloidosis is recognized as a serious complication of rheumatoid arthritis or inflammatory bowel disease, but also of inflammatory skin disease. However, the detailed molecular mechanism of amyloidosis associated with cutaneous inflammation remains unclear, and therapeutic approaches are limited. Here, we investigated the pathophysiology of amyloidosis secondary to cutaneous inflammation and the therapeutic effects of Janus kinase (JAK) inhibitors by examining a mouse model of spontaneous dermatitis (KCASP1Tg mice). Moreover, KCASP1Tg mice were crossed with interleukin-17A (IL-17A) knockout mice to generate IL-17A-/KCASP1Tg and examine the role of IL-17A in amyloidosis under cutaneous inflammation. KCASP1Tg mice showed severe amyloid deposition in the liver and spleen. Increased serum-neutral fat levels and decreased lymphocyte production were observed in the spleen. Overproduction of amyloidosis was partially ameliorated by the administration of JAK inhibitors and was further improved in IL-17A-/KCASP1Tg mice. IL-17A-producing cells included CD4, gamma delta, and CD8 T cells. In summary, our results from the analysis of a mouse model of dermatitis revealed that skin-derived inflammatory cytokines can induce amyloid deposition in the liver and spleen, and that the administration of JAK inhibitors and, even more, IL-17A ablation, reduced amyloidosis. This study demonstrates that active control of skin inflammation is essential to prevent internal organ amyloidosis.
35411981 Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a rando 2022 Apr 12 BACKGROUND: Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events. OBJECTIVE: To identify risk factors for ADAb in the early phase of infliximab treatment. METHODS: Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders. RESULTS: ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0-3.6]) and lifetime smoking (OR, 2.0 [CI 1.1-3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2-0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2-0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0-1.1]) and "drug holidays" of more than 11 weeks (OR, 4.1 [CI 1.2-13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0-0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6-0.8]) reduced the risk of immunogenicity. CONCLUSION: Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.
35314766 Smartphone applications for informal caregivers of chronically ill patients: a scoping rev 2022 Mar 21 Mobile-health applications can be used to deliver timely and personalized health information to family and friends of chronically ill adults living in the community. This scoping review aims to investigate the nature and extent of native smartphone applications for informal caregivers. Six databases were searched for articles on applications across ten chronic conditions, namely heart disease, stroke, cancer, chronic obstructive respiratory disease, asthma, diabetes, Alzheimer's disease or other dementia, rheumatoid arthritis, hypertension, and mood or anxiety disorders. In total, 36 articles were included, encompassing 26 applications. Of these, smartphone applications were designed for use only by caregivers (n = 15), with a few applications also intended to be used with patients (n = 5), healthcare providers (n = 4), or all three roles (n = 2). Most applications targeted a single chronic condition (n = 25), with Alzheimer's and other dementia being the most common (n = 18). Only one application was designed for management of multiple chronic conditions. Long-term evaluation methods are needed to continually assess the impact of applications on a range of process and health outcomes, such as usability, caregiver burden, and quality of life. Additional directions to advance native smartphone applications for caregivers are discussed, including personalization and expansion of eligibility criteria.
35291510 Cardiac conduction disturbances in rheumatologic disease: a cross-sectional study. 2022 BACKGROUND: Cardiovascular abnormalities are common in patients with rheumatologic disorders. Tachy-arrhythmias occur more frequently in these patients than the general population; however, the prevalence of bradyarrhythmias in this group is less clear. This investigation aimed to analyze the incidence and predictors of bradyarrhythmias and conduction disturbances, as well as the presence and influence of cardiologist management, in patients with rheumatologic disorders. METHODS: We performed a retrospective chart review of 57 consecutive patients with rheumatologic conditions evaluated at a tertiary-care safety-net hospital. Conduction disturbances were defined by any electrocardiogram (ECG) finding indicating: bradycardia, sinoatrial block of any degree, atrioventricular nodal block of any degree, left anterior or posterior fascicular block, non-specific intraventricular conduction delay, complete or incomplete right bundle branch block, left bundle branch block, or paced rhythm. Univariate and multivariate analyses were used to assess the association of relative predictors of conduction disturbance, the primary outcome of this investigation, as well as the secondary outcome of cardiologist involvement in patient care. Statistical significance was defined as P<0.05. Variables found to be statistically significant in a univariate analysis were included in a multivariable logistic regression analysis. RESULTS: The most common rheumatologic condition in our patient population was systemic lupus erythematous (21 patients, 36.8%) followed by gout (15 patients, 26.3%), rheumatoid arthritis (13 patients, 22.8%), sarcoidosis (6 patients, 10.5%), and two patients (3.5%) with other autoimmune diseases. A total of 31.6% of patients in this study were found to have conduction disturbances, higher than the prevalence of conduction disturbances in the general population. Multivariate logistic regression analysis showed significantly increased odds for conduction disturbances with increased age (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.01-1.10, P<0.05). Similar analysis for the involvement of a cardiologist in the care of a patient with a rheumatologic disorder found increased odds for cardiologist involvement with advanced age (OR: 1.05, 95% CI: 1.002-1.09, P<0.05) and cardiovascular disease (OR: 5.0, 95% CI 1.24-21.90, P<0.05). CONCLUSION: Prevalence of conduction abnormalities is greater in rheumatologic patients than the general population. Odds for conduction abnormalities increased with age; and the odds of cardiologist involvement increased with age and cardiovascular disease.
35245413 A systematic review and narrative synthesis of footwear and orthotic devices used in the m 2022 May INTRODUCTION: Haemarthrosis is a clinical feature of haemophilia leading to haemarthropathy. The ankle joint is most commonly affected, resulting in significant pain, disability and a reduction in health-related quality of life. Footwear and orthotic devices are effective in other diseases that affect the foot and ankle, such as rheumatoid arthritis, but little is known about their effect in haemophilia. AIMS: To review the efficacy and effectiveness of footwear and orthotic devices in the management of ankle joint haemarthrosis and haemarthropathy in haemophilia. METHODS: A systematic literature review was conducted. Two review authors independently screened studies for inclusion and appraised methodological quality using Joanna Briggs Institute Critical Appraisal checklists. A narrative analysis was undertaken. RESULTS: Ten studies involving 271 male participants were eligible for inclusion. All studies were quasi-experimental; three employed a within-subject design. Two studies included an independent comparison or control group. A range of footwear and orthotic devices were investigated. Limited evidence from non-randomised studies suggested that footwear and orthotic devices improve the number of ankle joint bleeding episodes, gait parameters and patient-reported pain. CONCLUSION: This review demonstrates a lack of robust evidence regarding the efficacy and effectiveness of footwear and orthotic devices in the management of ankle joint haemarthrosis and haemarthropathy in haemophilia. Methodological heterogeneities and limitations with the study designs, small sample sizes and limited follow-up of participants exist. Future studies utilising randomised designs, larger sample sizes, long-term follow-up and validated patient-reported outcome measures are needed to inform the clinical management of ankle joint haemarthrosis and haemarthropathy.
35153504 Development of a Nomogram for Predicting Very Low Bone Mineral Density (T-Scores <-3) in t 2022 PURPOSE: Fragility fractures, the most serious complication of osteoporosis, affect life quality and increase medical expenses and economic burden. Strategies to identify populations with very low bone mineral density (T-scores <-3), indicating very high fracture risk according to the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE), are necessary to achieve acceptable fracture risk levels. In this study, the characteristics of persons with T-scores <-3 were analyzed in the Chinese population to identify risk factors and develop a nomogram for very low bone mineral density (T-scores <-3) identification. MATERIALS AND METHODS: We conducted a cross-sectional study using the datasets of the Health Improvement Program of Bone (HOPE), with 602 men aged ≥50 years and 482 postmenopausal women. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Data on clinical risk factors, including age, sex, weight, height, previous fracture, parental hip fracture history, smoking, alcohol intake >3 units/day, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis were collected. A multivariate logistic regression to evaluate the relationship between the clinical risk factors and very low BMD (T-scores <-3) was conducted. Parameter estimates of the final model were then used to construct a nomogram. RESULTS: Sixty-three of 1084 participants (5.8%) had BMD T-score <-3. In multivariable regression analysis, age (odds ratio [OR] = 1.068, 95% confidence interval [CI]: 1.037-1.099) and weight (OR = 0.863, 95% CI: 0.830-0.897) were significant factors that were associated with very low BMD (T-scores <-3). These variables were the factors considered in developing the nomogram. The area under the receiver operating characteristic (ROC) curve for the model was 0.861. The cut-off value of the ROC curve was 0.080. CONCLUSION: The nomogram can effectively assist clinicians to identify persons with very low BMD (T-scores <-3) and very high fracture risk in the Chinese population.
35053839 Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symp 2022 Jan 12 Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic-vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune-autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.
34910207 Negative effect of anger on chronic pain intensity is modified by multiple mood states oth 2022 Apr 18 OBJECTIVES: To investigate whether mood states other than anger can modify the association between anger and pain intensity in individuals with chronic pain. METHODS: We analysed 22,059 participants with chronic pain, including 214 participants with rheumatoid arthritis (RA), who completed a questionnaire. The Profile of Mood States short form (POMS-SF) was used to assess six dimensions of mood states (anger-hostility, tension-anxiety, depression-dejection, confusion, fatigue, and vigour). A numerical rating scale (NRS) assessed pain intensity. We examined the association between anger-hostility and the NRS and the relationship between POMS-SF components. Moderation analyses were used to investigate whether the five mood states other than anger-hostility modified the effect of anger-hostility on the NRS. RESULTS: Anger-hostility contributed to pain intensity. Although increased mood states other than vigour were associated with increased pain intensity, these increased mood states appeared to suppress the effect of anger-hostility on pain intensity. Increased vigour was associated with decreased pain intensity and increased the effect of anger-hostility on pain intensity. CONCLUSIONS: Mood states other than anger may influence the association between anger and pain intensity in individuals with chronic pain. It is important to focus on complicated mood states and anger in individuals with chronic pain, including RA.