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Rheumatology and Therapy Apr 2024This study aimed to characterize patient-reported outcomes from social media conversations in the gout community. The impact of management strategy differences on the...
INTRODUCTION
This study aimed to characterize patient-reported outcomes from social media conversations in the gout community. The impact of management strategy differences on the community's emotional states was explored.
METHODS
We analyzed two social media sources using a variety of natural language processing techniques. We isolated conversations with a high probability of discussing disease management (score > 0.99). These conversations were stratified by management type: proactive or reactive. The polarity (positivity/negativity) of language and emotions conveyed in statements shared by community members was assessed by management type.
RESULTS
Among the statements related to management, reactive management (e.g., urgent care) was mentioned in 0.5% of statements, and proactive management (e.g., primary care) was mentioned in 0.6% of statements. Reactive management statements had a significantly larger proportion of negative words (59%) than did proactive management statements (44%); "fear" occurred more frequently with reactive statements, whereas "trust" predominated in proactive statements. Allopurinol was the most common medication in proactive management statements, whereas reactive management had significantly higher counts of prednisone/steroid mentions.
CONCLUSIONS
A unique aspect of examining gout-related social media conversations is the ability to better understand the intersection of clinical management and emotional impacts in the gout community. The effect of social media statements was significantly stratified by management type for gout community members, where proactive management statements were characterized by more positive language than reactive management statements. These results suggest that proactive disease management may result in more positive mental and emotional experiences in patients with gout.
PubMed: 38253955
DOI: 10.1007/s40744-023-00637-y -
European Journal of Pharmacology Mar 2024Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, and oxidative modification cause endothelial damage,... (Review)
Review
Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, and oxidative modification cause endothelial damage, triggering innate and adaptive immune responses. Recruited immune cells orchestrate the early atherosclerotic lesions by releasing proinflammatory cytokines, expediting the foam cell formation, intraplaque haemorrhage, secretion of matrix-degrading enzymes, and lesion progression, eventually promoting coronary artery syndrome via various inflammatory cascades. In addition, soluble mediators disrupt the dynamic anti- and prothrombotic balance maintained by endothelial cells and pave the way for coronary artery disease such as angina pectoris. Recent studies have established a relationship between elevated levels of inflammatory markers, including C-reactive protein (CRP), interleukins (IL-6, IL-1β), and tumour necrosis factor-alpha (TNF-α) with the severity of CAD and the possibility of future cardiovascular events. High-sensitivity C-reactive protein (hs-CRP) is a marker for assessing systemic inflammation and predicting the risk of developing CAD based on its peak plasma levels. Hence, understanding cross-talk interactions of inflammation, atherogenesis, and CAD is highly warranted to recalculate the risk factors that activate and propagate arterial lesions and devise therapeutic strategies accordingly. Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 and IL-6 (canakinumab and tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine and xanthene oxidase inhibitor (allopurinol) have shown promising results in reducing inflammation, regressing atherogenic plaque and modifying the course of CAD. Here, we review the complex interplay between inflammatory, endothelial, smooth muscle and foam cells. Moreover, the putative role of inflammation in atherosclerotic CAD, underlying mechanisms and potential therapeutic implications are also discussed herein.
Topics: Humans; Coronary Artery Disease; C-Reactive Protein; Interleukin-6; Endothelial Cells; Atherosclerosis; Inflammation
PubMed: 38242225
DOI: 10.1016/j.ejphar.2024.176338 -
Open Access Rheumatology : Research and... 2024The prevalence of gout has increased in the Western societies due to ageing and increasing BMI. Recently, lifestyle and dietary factors have been linked in...
BACKGROUND
The prevalence of gout has increased in the Western societies due to ageing and increasing BMI. Recently, lifestyle and dietary factors have been linked in epidemiological studies with an alteration of the risk of gout; however, there remains a lack of data on patient knowledge of these factors. The purpose of this survey-based study was to determine the knowledge of gout and its treatment both in the community and specialist care settings.
METHODS
Participants were recruited from a hospital rheumatology outpatient department, consumer organization and a random sample of participants from a population-based cohort who had self-reported gout in South Australia. Participants completed a survey regarding basic demographics, the Single Item Literacy Screener, use of medication and diet for treatment of their gout and knowledge of gout.
RESULTS
Seventy-four people were recruited (87% male) with a mean age of 66 years (range 35-88). The mean duration of gout was 16.6 years (range 0-60). On screening with SILS, 19.0% were identified as having limited reading ability. Most gout was managed by the family practitioner (81.1%) and/or rheumatologist (18.9%). In regard to current gout medications, 52.7% were taking allopurinol, 17.6% colchicine, 9.5% non-steroidal anti-inflammatory drugs, 6.8% prednisolone and 5.4% herbal preparations. For further information regarding gout, participants would most commonly approach their general practitioner (85.1%). Most participants correctly identified certain triggers to gout attacks and almost half of participants (41.9%) reported that they had altered their diet due to gout. Conversely, participants often incorrectly identified common risk or protective factors for gout.
CONCLUSION
Gout remains a common, yet undertreated, chronic condition. Our study highlights a lack of knowledge amongst patients of risk and protective factors in relation to gout. The increasing prevalence of gout within the population indicates a need to improve education and understanding among those with the condition.
PubMed: 38239283
DOI: 10.2147/OARRR.S435692 -
Redox Biology Apr 2024Extracellular high mobility group box 1 (HMGB1) is a key mediator in driving allergic airway inflammation and contributes to asthma. Yet, mechanism of HMGB1 secretion in...
BACKGROUND
Extracellular high mobility group box 1 (HMGB1) is a key mediator in driving allergic airway inflammation and contributes to asthma. Yet, mechanism of HMGB1 secretion in asthma is poorly defined. Pulmonary metabolic dysfunction is recently recognized as a driver of respiratory pathology. However, the altered metabolic signatures and the roles of metabolic to allergic airway inflammation remain unclear.
METHODS
Male C57BL/6 J mice were sensitized and challenged with toluene diisocyanate (TDI) to generate a chemically induced asthma model. Pulmonary untargeted metabolomics was employed. According to results, mice were orally administered allopurinol, a xanthine oxidase (XO) inhibitor. Human bronchial epithelial cells (16HBE) were stimulated by TDI-human serum albumin (HSA).
RESULTS
We identified the purine metabolism was the most enriched pathway in TDI-exposed lungs, corresponding to the increase of xanthine and uric acid, products of purine degradation mediated by XO. Inhibition of XO by allopurinol ameliorates TDI-induced oxidative stress and DNA damage, mixed granulocytic airway inflammation and Th1, Th2 and Th17 immunology as well as HMGB1 acetylation and secretion. Mechanistically, HMGB1 acetylation was caused by decreased activation of the NAD-sirtuin 1 (SIRT1) axis triggered by hyperactivation of the DNA damage sensor poly (ADP-ribose)-polymerase 1 (PARP-1). This was rescued by allopurinol, PARP-1 inhibitor or supplementation with NAD precursor in a SIRT1-dependent manner. Meanwhile, allopurinol attenuated Nrf2 defect due to SIRT1 inactivation to help ROS scavenge.
CONCLUSIONS
We demonstrated a novel regulation of HMGB1 acetylation and secretion by purine metabolism that is critical for asthma onset. Allopurinol may have therapeutic potential in patients with asthma.
Topics: Humans; Male; Mice; Animals; Allopurinol; Xanthine Oxidase; HMGB1 Protein; Sirtuin 1; Poly(ADP-ribose) Polymerase Inhibitors; NAD; Mice, Inbred C57BL; Asthma; Enzyme Inhibitors; Inflammation; Disease Models, Animal
PubMed: 38219573
DOI: 10.1016/j.redox.2023.103021 -
Seminars in Arthritis and Rheumatism Apr 2024There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare.
METHODS
This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680.
RESULTS
A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment.
CONCLUSION
There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.
Topics: Adult; Humans; Uric Acid; Gout Suppressants; Gout; Allopurinol; Pain; Randomized Controlled Trials as Topic
PubMed: 38215627
DOI: 10.1016/j.semarthrit.2024.152367 -
Journal of Traditional Chinese Medicine... Feb 2024To evaluate the effect of Dahuang Mudan Tang (, DHMD) and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide...
Combination of allopurinol with Dahuang Mudan Tang significantly improve kidney function and alleviate oxidative stress and inflammation of chronic kidney disease stage Ⅰ-Ⅲ patients with hyperuricemia.
OBJECTIVE
To evaluate the effect of Dahuang Mudan Tang (, DHMD) and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinical management of chronic kidney disease complications.
METHODS
A total of 80 chronic kidney patients staged G1-G3b with hyperuricemia were randomly grouped to receive single allopurinol treatment (control) and combined treatment with DHMD (treated) for 8 weeks. The kidney function and proteinuria indicators of patients were compared between pre-and post-treatment. The oxidative stress and inflammation responses were evaluated by corresponding indicators and cytokines. The clinical efficiency rate and adverse reaction events were also summarized to assess the therapeutic efficiency and safety.
RESULTS
The kidney function and proteinuria of enrolled patients were alleviated after their therapies, behaved as the increasing estimated glomerular filtration rate and decreasing serum creatinine, serum uric acid, urea nitrogen, 24 h urine protein levels. On the other hand, the malondialdehyde level and pro-inflammation cytokines were suppressed by the therapies, and the superoxide dismutase was found to be significantly enhanced. Patients in the treated groups showed a better recovery in kidney function, proteinuria, oxidative stress, and inflammation response. Moreover, patients in the treated group showed a higher efficiency rate (95%) and fewer adverse reaction events (5%).
CONCLUSIONS
The combination of allopurinol with DHMD significantly promoted the recovery of chronic kidney disease stage G1-G3b patients with hyperuricemia, which can be considered a novel clinical therapeutic strategy.
Topics: Humans; Allopurinol; Hyperuricemia; Uric Acid; Treatment Outcome; Renal Insufficiency, Chronic; Proteinuria; Oxidative Stress; Kidney; Inflammation; Cytokines
PubMed: 38213253
DOI: 10.19852/j.cnki.jtcm.20231121.001 -
PloS One 2024Allopurinol, the first-line treatment for chronic gout, is a common causative drug for severe cutaneous adverse reactions (SCAR). HLA-B*58:01 allele was strongly...
INTRODUCTION
Allopurinol, the first-line treatment for chronic gout, is a common causative drug for severe cutaneous adverse reactions (SCAR). HLA-B*58:01 allele was strongly associated with allopurinol-induced SCAR in Asian countries such as Taiwan, Japan, Thailand and Malaysia. HLA-B*58:01 screening before allopurinol initiation is conditionally recommended in the Southeast-Asian population, but the uptake of this screening is slow in primary care settings, including Malaysia. This study aimed to explore the views and experiences of primary care doctors and patients with gout on implementing HLA-B*58:01 testing in Malaysia as part of a more extensive study exploring the feasibility of implementing it routinely.
METHODS
This qualitative study used in-depth interviews and focus group discussions to obtain information from patients with gout under follow-up in primary care and doctors who cared for them. Patients and doctors shared their gout management experiences and views on implementing HLA-B*58:01 screening in primary care. Data were coded and analysed using thematic analysis.
RESULTS
18 patients and 18 doctors from three different healthcare settings (university hospital, public health clinics, private general practitioner clinics) participated. The acceptability to HLA-B*58:01 screening was good among the doctors and patients. We discovered inadequate disclosure of severe side effects of allopurinol by doctors due to concerns about medication refusal by patients, which could potentially be improved by introducing HLA-B*58:01 testing. Barriers to implementation included out-of-pocket costs for patients, the cost-effectiveness of this implementation, lack of established alternative treatment pathway besides allopurinol, counselling burden and concern about genetic data security. Our participants preferred targeted screening for high-risk populations instead of universal screening.
CONCLUSION
Implementing HLA-B*58:01 testing in primary care is potentially feasible if a cost-effective, targeted screening policy on high-risk groups can be developed. A clear treatment pathway for patients who test positive should be made available.
Topics: Humans; Allopurinol; Gout; HLA-B Antigens; Drug-Related Side Effects and Adverse Reactions; Thailand; Primary Health Care
PubMed: 38206925
DOI: 10.1371/journal.pone.0296498 -
The American Journal of Case Reports Jan 2024BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare hypersensitivity reaction involving the skin and various visceral organs; the... (Review)
Review
BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare hypersensitivity reaction involving the skin and various visceral organs; the kidneys are the second most affected organ. Many drugs are reported to be associated with DRESS, particularly antiepileptic agents and allopurinol. Certain human leukocyte antigen (HLA) haplotypes, in combination with a particular drug, can further contribute to an increased risk of DRESS. Symptoms often develop 2 to 8 weeks after drug initiation. If diagnosis is delayed, DRESS can be a life-threatening condition. CASE REPORT We present cases of 2 patients. The first patient was an 86-year-old Polish woman who developed acute kidney injury and skin lesions with accompanying leucocytosis and eosinophilia during long-term antibiotic therapy with piperacillin/tazobactam and ciprofloxacin. The second patient was a 37-year-old Asian woman with predialysis chronic renal disease stage V in the course of IgA nephropathy. Two weeks after starting allopurinol in a standard dose, she presented with maculopapular rash, facial edema, fever, liver injury, and eosinophilia. Renal function started to deteriorate, but she did not require dialysis. In both cases, the discontinuation of the above-mentioned drugs and the introduction of steroid therapy and intravenous immunoglobulins allowed for clinical improvement and recovery. In the second case, the extended 4-locus HLA typing was performed retrospectively, and allele HLA-B*5801 was found. CONCLUSIONS Due to the rare occurrence and heterogeneous manifestation of DRESS, its diagnosis can pose many difficulties. In-depth analysis of symptoms, medicines taken, and laboratory findings enable the implementation of appropriate treatment and recovery.
Topics: Female; Humans; Aged, 80 and over; Adult; Allopurinol; Drug Hypersensitivity Syndrome; Retrospective Studies; Renal Dialysis; Eosinophilia; Angioedema
PubMed: 38204155
DOI: 10.12659/AJCR.942315 -
European Review For Medical and... Dec 2023Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout.
MATERIALS AND METHODS
PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test.
RESULTS
According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs.
CONCLUSIONS
The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.
Topics: Humans; Allopurinol; Benzbromarone; Chemical and Drug Induced Liver Injury; China; Febuxostat; Gout; Gout Suppressants; Hyperuricemia; Treatment Outcome; Uric Acid; Uricosuric Agents
PubMed: 38164861
DOI: 10.26355/eurrev_202312_34797 -
Life (Basel, Switzerland) Nov 2023Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction commonly related to eosinophilia, from uncertain epidemiology, and without...
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction commonly related to eosinophilia, from uncertain epidemiology, and without consensus for diagnosis and treatment globally. It presents a great challenge in its management and is characterized by fever, lymphadenopathy, skin rash, and multisystemic involvement. An aggressive and difficult-to-manage clinical case is presented in a 50-year-old man with chronic kidney disease due to diabetes mellitus type 2 and systemic arterial hypertension, who developed an unusual variant similar to DRESS and Stevens-Johnson syndrome (SJS) overlap secondary to allopurinol, with skin manifestations without eosinophilia, but fulfilling clinical and laboratory criteria for DRESS and SJS syndrome.
PubMed: 38137852
DOI: 10.3390/life13122251