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1.
BMC Med ; 19(1): 265, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34749717

RESUMO

BACKGROUND: Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs). METHODS: In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence. RESULTS: The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p > 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p = 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p = 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p = 0.003), and 6 months, 29.5 vs. 34.5 (p = 0.03), respectively. CONCLUSIONS: A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout. TRIAL REGISTRATION: Registered at ClinicalTrials.gov NCT02741700.


Assuntos
Gota , Veteranos , Afro-Americanos , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Ácido Úrico
3.
Jt Dis Relat Surg ; 32(3): 771-774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34842112

RESUMO

Surgical site gout is an extremely rare complication that is difficult to diagnose, particularly in patients without a history of gout. A 57-year-old male patient was admitted with no previous history of gout, complaining of surgical site gout located at the junction where flexor carpi ulnaris tendon was transferred to extensor digitorum communis tendon after 33 years of the initial surgery. The patient was presented with a progressive swelling over the last three months which was located on the dorsoulnar side of the right wrist joint. Magnetic resonance imaging revealed an iso/hypointense mass. During the excisional biopsy, retained non-absorbable suture materials were observed within the mass. Histopathological examination result was reported as a typical gout tophus. No recurrence was observed after 18 months of follow-up. In conclusion, surgical site gout may be observed at transferred tendons years after the initial surgery.


Assuntos
Gota , Tendões , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transferência Tendinosa , Tendões/diagnóstico por imagem , Tendões/cirurgia , Punho
4.
N Z Med J ; 134(1543): 51-58, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34695076

RESUMO

AIM: Gout is a health equity issue for Maori and Pacific peoples because disparities in quality of care exist. This study aims to describe domains of access that may contribute to the optimisation of gout care and, therefore, address health inequity. METHODS: The practice management system at one general practice in Auckland was used to identify enrolled patients with gout, using disease codes and medication lists. Barriers to access for the cohort were investigated using staff knowledge and the practice management system. The general practice is uniquely situated within an urban marae (traditional meeting house) complex serving a predominantly Maori community. This enables a focus on domains of access other than cultural safety. RESULTS: Of 3,095 people enrolled at the practice, 268 were identified as having gout. Of these, 94% had at least one other long-term health condition. The majority of people with gout enrolled at the practice have employment roles incongruent with the clinic's opening hours. CONCLUSIONS: Social circumstances, such as employment and availability of transport, should be actively discussed with all patients and recorded in the practice management system. Reorientation of health services, including hours of access, is evidentially required to ensure optimal management of gout and possibly other health conditions.


Assuntos
Serviços Comunitários de Farmácia/organização & administração , Gota/tratamento farmacológico , Gota/etnologia , Equidade em Saúde/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Medicina Geral/economia , Supressores da Gota/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Grupo com Ancestrais Oceânicos
5.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638981

RESUMO

MUC1 is a transmembrane mucin involved in carcinogenesis and cell signaling. Functional MUC1 variants are associated with multiple metabolic and biochemical traits. This study investigated the association of functional MUC1 variants with MUC1 DNA methylation and various metabolic, biochemical, and hematological parameters. In total, 80,728 participants from the Taiwan Biobank were enrolled for association analysis using functional MUC1 variants and a nearby gene regional plot association study. A subgroup of 1686 participants was recruited for MUC1 DNA methylation analysis. After Bonferroni correction, we found that two MUC1 variants, rs4072037 and rs12411216, were significantly associated with waist circumference, systolic blood pressure, hemoglobin A1C, renal functional parameters (blood urea nitrogen, serum creatinine levels, and estimated glomerular filtration rate), albuminuria, hematocrit, hemoglobin, red blood cell count, serum uric acid level, and gout risk, with both favorable and unfavorable effects. Causal inference analysis revealed that the association between the variants and gout was partially dependent on the serum uric acid level. Both gene variants showed genome-wide significant associations with MUC1 gene-body methylation. Regional plot association analysis further revealed lead single-nucleotide polymorphisms situated at the nearby TRIM46-MUC1-THBS3-MTX1 gene region for the studied phenotypes. In conclusion, our data demonstrated the pleiotropic effects of MUC1 variants with novel associations for gout, red blood cell parameters, and MUC1 DNA methylation. These results provide further evidence in understanding the critical role of TRIM46-MUC1-THBS3-MTX1 gene region variants in the pathogenesis of cardiometabolic, renal, and hematological disorders.


Assuntos
Pressão Sanguínea , Pleiotropia Genética , Gota/sangue , Gota/genética , Rim/fisiopatologia , Mucina-1/genética , Polimorfismo de Nucleotídeo Único , Adulto , Aterosclerose/epidemiologia , Aterosclerose/genética , Glicemia/análise , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , Metilação de DNA/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Gota/epidemiologia , Gota/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan/epidemiologia , Ácido Úrico/sangue , Circunferência da Cintura
6.
Trials ; 22(1): 743, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702311

RESUMO

BACKGROUND: The prevalence of renal calculi in patients with gout is high. Alkalized urine has been recommended by the 2020 European Association of Urology (EAU) guidelines to promote calculus dissolution. However, randomized controlled trials are lacking. METHODS: In the protocol of this randomized, placebo-controlled, double-blinded trial, patients with gout combined with renal calculi are randomized (1:1) to the placebo and sodium bicarbonate groups. The intervention would be performed for 24 weeks, the 1-12 weeks are double-blinded, and the 13-24 weeks are open-labeled. Sodium bicarbonate (1 g tid) will be performed for 24 weeks in the sodium bicarbonate group. The placebo will be performed for 12 weeks and not be performed from 13 weeks to 24 weeks in the placebo group. All subjects will be administered febuxostat (40 mg/day) for 24 weeks and receive concomitant anti-inflammatory prophylaxis therapy for 12 weeks. The primary outcome is the proportion of patients whose renal calculus volume will be reduced after 12 weeks of treatment. The secondary outcomes include the volume changes of renal calculi, uric acid changes, the proportion of patients with serum uric acid (sUA) levels < 360 µmol/L, the changes in estimated glomerular filtration rate (eGFR), the pH value of urine, and the incidence of adverse events after treatment for 12 and 24 weeks. DISCUSSION: This study will evaluate the efficacy and safety of sodium bicarbonate-alkalized urine on renal calculi in patients with gout. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2100045183. Registered on April 7, 2021, with ChiCTR.


Assuntos
Gota , Cálculos Renais , Método Duplo-Cego , Febuxostat/uso terapêutico , Gota/diagnóstico , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Humanos , Cálculos Renais/diagnóstico , Cálculos Renais/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ácido Úrico
7.
Maturitas ; 153: 33-40, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34654526

RESUMO

OBJECTIVES: While gout is a well-known entity, little research has been conducted on its pathophysiology. There is growing evidence that women with hyperuricemia are at higher cardiovascular risk than men with hyperuricemia. We aim to evaluate whether gender-specific cut-offs should be considered. STUDY DESIGN: Cross-sectional study (the German Health Interview and Examination Survey for Adults; DEGS1). MAIN OUTCOME MEASURES: Self-reported gout or hyperuricemia and uric acid level. RESULTS: Of 6,918 participants (mean age 47.2 years; 50.5% females), 9.7% had had a diagnosis of hyperuricemia or gout at least once in their lifetime. Men were nearly twice as often affected as women (12.9 vs. 6.5%). In women, the prevalence of cardiovascular and renal diseases increased with higher uric acid level to a much greater extent than in men. This association remained in multivariate analyses. CONCLUSIONS: No commonly accepted cut-off value for uric acid has been established. Overall, women were at lower risk of hyperuricemia. However, women were at higher risk of having cardiovascular and renal comorbidities, even at lower uric acid levels. Our results are in line with the accumulating evidence that we should consider gender in gout and hyperuricemia.


Assuntos
Gota/epidemiologia , Hiperuricemia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Alemanha/epidemiologia , Gota/complicações , Humanos , Hiperuricemia/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Ácido Úrico/sangue , Adulto Jovem
8.
Sci Rep ; 11(1): 17799, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493793

RESUMO

Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (rg). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P-value = 1.2E-17; rg = 0.25 [P-value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P-value = 1.2E-21; rg = 0.23 [P-value = 8.8E-12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = - 0.083; 95% CI = - 0.101, - 0.065; P-value = 2.5E-19; rg = - 0.28; [P-value = 5.2E-24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P-value = 8.9E-14; rg = 0.29 [P-value = 0.001]) and higher HDL decreased urate (beta = - 0.109; 95% CI = - 0.148, - 0.071; P-value = 2.7E- 08; rg = - 0.21 [P-value = 9.8E-05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P-value = 1.1E-130; rg = 0.89 [P-value = 1.7E-55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P-value = 1.3E-04; rg = 0.23 [P-value = 2.7E-05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = -0.011; 95% CI = -0.030, 0.008; P-value = 2.6E-01; rg = 0.03 [P-value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity's impact on urate was exacerbated by it decreasing HDL.


Assuntos
Gota/genética , Análise da Randomização Mendeliana , Obesidade/genética , Ácido Úrico/metabolismo , Causalidade , Estudo de Associação Genômica Ampla , Gota/metabolismo , Gota/prevenção & controle , Humanos , Desequilíbrio de Ligação , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Metanálise como Assunto , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único , Triglicerídeos/metabolismo
9.
PLoS One ; 16(9): e0257082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534233

RESUMO

BACKGROUND: The conventional one-size-fits-all approach has been criticized for almost all drugs used especially for chronic diseases, including gout. The present study was aimed to explore the need of individualization and optimization of the dose of anti-gout medications among gout patients. METHODS: Cross-sectional study was carried out among 384 randomly selected new gout patients visiting two gout treatment centers at Lalitpur Metropolitan City, Nepal and who were taking antigout medications. Patients not taking anti-gout medications and not showing willingness to participate were excluded. The eGFR was calculated with the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation (2009). Doses to be individualized were decided based on the Renal Drug Handbook and verified with the BNF 80. Data were analyzed via R 4.0.3 by applying the multinomial logistic regression to analyze statistical significance of risk with various predictors, and considering a p-value <0.05 statistically significant. Comorbidities were coded as per the ICD-11 coding and medicines were coded according to the WHO Guidelines for ATC classification and DDD assignment 2020. RESULTS: The high risk of progression to CKD increased in the age range 54-63 and ≥84 years by 17.77 and 43.02 times, respectively. Also, high risk increased by 29.83 and 20.2 times for the overweight and the obese respectively. Aceclofenac 100mg was prescribed for maximum patients (30.5%). Need of dose individualization was realized in 30 patients, with maximum (7) in case of etoricoxib 90mg. Various glucocorticoids were prescribed for 36.9% patients, out of whom 3.8%required dose individualization and 15.9% patients with xanthine oxidase inhibitors, out of whom 1.3% required dose individualization. CONCLUSION: Thirty cases required dose individualization, which was although minimal but could have meaningful impact on the clinical success of the individual patient. Based on the recommendation on dose individualization, those patients could be optimized on their therapy on future follow ups.


Assuntos
Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Adulto , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/patologia , Fatores de Risco
10.
Ann Palliat Med ; 10(10): 10327-10337, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34498481

RESUMO

BACKGROUND: To evaluate the major cardiovascular (CV) events of febuxostat compared to allopurinol for the treatment of gout or asymptomatic hyperuricemia. METHODS: Relevant studies published until August 15, 2020 were identified by a systematic search of the PubMed and Wiley Online Library databases. Any controlled clinical trial, randomised controlled trial (RCT), retrospective cohort study or open label trial (OLT) comparing febuxostat in patients with gout or hyperuricemia with allopurinol. The quality of all identified studies was assessed based on Cochrane Collaboration's risk of bias tool. Odds ratios (OR) were calculated with random effects and reported with corresponding 95% confidence intervals (CI). RESULTS: Eighteen studies were ultimately included in the analysis, among them 6 articles mentioned serum uric acid (sUA) level before and after treatment, 14 articles mentioned major cardiovascular events, 5 articles mentioned cardiovascular death, 6 articles mentioned skin reactions, 6 articles mentioned musculoskeletal and connective tissue signs and symptoms, 4 articles mentioned joint-related signs and symptoms, 6 articles mentioned upper respiratory infection, 5 articles mentioned gastrointestinal reaction and 7 articles mentioned all-cause mortality. The febuxostat group showed significantly lower sUA levels than allopurinol group (MD =-0.83, 95% CI: -1.22 to -0.44, P<0.0001, I2=98%). There was no markedly difference between the febuxostat and allopurinol (OR 1.01, 95% CI: 0.83 to 1.23, P=0.84, I2=95%) in the major cardiovascular events. The occurrence of skin reactions of febuxostat was significantly fewer than allopurinol (OR 0.55, 95% CI: 0.42 to 0.73, P<0.0001, I2=49%). Regarding to occurrence of CV death, musculoskeletal and connective tissue signs and symptoms, febuxostat group was higher than allopurinol group. However, among patients with gout or hyperuricemia, treatment with febuxostat resulted in other adverse reactions, including all-causes mortality similar to those associated with allopurinol. DISCUSSION: The limitation of the study was the included studies show high heterogeneity in regard to their design. There was no difference in the incidence of major cardiovascular events between febuxostat and allopurinol, and febuxostat was better in lowering uric acid and has less adverse skin reactions than allopurinol, but the risk of CV death of febuxostat was higher than allopurinol.


Assuntos
Doenças Cardiovasculares , Gota , Hiperuricemia , Alopurinol/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/tratamento farmacológico , Febuxostat/efeitos adversos , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Humanos , Hiperuricemia/tratamento farmacológico , Resultado do Tratamento , Ácido Úrico
11.
J Control Release ; 338: 804-812, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481925

RESUMO

Pegloticase is an enzyme used to reduce serum uric acid levels in patients with chronic, treatment-refractory gout. Clinically, about 40% of patients develop high titers of anti-PEG antibodies (APA) after initial treatment, which in turn quickly eliminate subsequent doses of pegloticase from the systemic circulation and render the treatment ineffective. We previously found that pre-infusion with high MW free PEG (40 kDa) can serve as a decoy to saturate circulating APA, preventing binding to a subsequently administered dose of PEG-liposomes and restoring their prolonged circulation in mice, without any detectible toxicity. Here, we investigated the use of 40 kDa free PEG to restore the circulation of radio-labeled pegloticase in mice using longitudinal Positron Emission Tomography (PET) imaging over 4 days. Mice injected with pegloticase developed appreciable APA titers by Day 9, which further increased through Day 14. Compared to naïve mice, mice with pegloticase-induced APA rapidly cleared 89Zr-labeled pegloticase, with ~75% lower pegloticase concentrations in the circulation at four hours after treatment. The 96-h AUC in APA+ mice was less than 30% of the AUC in naïve mice. In contrast, pre-infusion of free PEG into PEG-sensitized mice restored the AUC of pegloticase to ~80% of that seen in naïve mice, resulting in a similar biodistribution to pegloticase in naïve mice over time. These results suggest that pre-infusion of free PEG may be a promising strategy to enable the safe and efficacious use of pegloticase and other PEGylated drugs in patients that have previously failed therapy due to induced APA.


Assuntos
Gota , Animais , Humanos , Camundongos , Polietilenoglicóis , Distribuição Tecidual , Urato Oxidase , Ácido Úrico
12.
Poult Sci ; 100(11): 101432, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547621

RESUMO

In recent years, goose gout, a severe infectious disease, has affected the development of the goose industry in China. Two different genotypes of goose astrovirus (GAstV), named as GAstV-1 and GAstV-2, were identified. GAstV-2 viruses are known to be the causative agent of goose gout; however, GAstV-1 has not been isolated, and the relationship between GAstV-1 and goose gout is unknown. One full genome sequence, designated as GAstV/CHN/TZ03/2019 (TZ03), was determined from the clinical tissue samples of a diseased gosling using next-generation sequencing. The complete genome of TZ03 was 7,262 nucleotides in length with typical genomic characteristics of avastroviruses. The TZ03 strain shares the highest identity (96.6%) with the GAstV-1 strain FLX, but only 51.5 to 61.3% identity with other astroviruses in Avastrovirus. Phylogenetic analysis revealed that the TZ03 strain clustered together with the GAstV-1 strains FLX and AHDY and was highly divergent from GAstV-2 viruses. The TZ03 strain was successfully isolated from goose embryos and caused 100% mortality of goose embryos after 5 passages. Electron microscopy showed that the virus particles were spherical with a diameter of ∼22 nm. The clinical symptoms were reproduced by experimental infection of healthy goslings, which were similar to those caused by GAstV-2 strains. Our data show that GAstV-1 is one of the causative agents of the ongoing goose gout disease in China. These findings enrich our understanding of the evolution of GAstVs that cause gout and provide potential options for developing biological products to treat goose gout.


Assuntos
Infecções por Astroviridae , Avastrovirus , Gota , Doenças das Aves Domésticas , Animais , Infecções por Astroviridae/epidemiologia , Infecções por Astroviridae/veterinária , Avastrovirus/genética , Galinhas , China/epidemiologia , Gansos , Gota/veterinária , Filogenia , Doenças das Aves Domésticas/epidemiologia
13.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502281

RESUMO

M. alba L. is a valuable nutraceutical plant rich in potential bioactive compounds with promising anti-gouty arthritis. Here, we have explored bioactives, signaling pathways, and key proteins underlying the anti-gout activity of M. alba L. leaves for the first-time utilizing network pharmacology. Bioactives in M. alba L. leaves were detected through GC-MS (Gas Chromatography-Mass Spectrum) analysis and filtered by Lipinski's rule. Target proteins connected to the filtered compounds and gout were selected from public databases. The overlapping target proteins between bioactives-interacted target proteins and gout-targeted proteins were identified using a Venn diagram. Bioactives-Proteins interactive networking for gout was analyzed to identify potential ligand-target and visualized the rich factor on the R package via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on STRING. Finally, a molecular docking test (MDT) between bioactives and target proteins was analyzed via AutoDock Vina. Gene Set Enrichment Analysis (GSEA) demonstrated that mechanisms of M. alba L. leaves against gout were connected to 17 signaling pathways on 26 compounds. AKT1 (AKT Serine/Threonine Kinase 1), γ-Tocopherol, and RAS signaling pathway were selected as a hub target, a key bioactive, and a hub signaling pathway, respectively. Furthermore, three main compounds (γ-Tocopherol, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine, and Lanosterol acetate) and three key target proteins-AKT1, PRKCA, and PLA2G2A associated with the RAS signaling pathway were noted for their highest affinity on MDT. The identified three key bioactives in M. alba L. leaves might contribute to recovering gouty condition by inactivating the RAS signaling pathway.


Assuntos
Supressores da Gota/farmacologia , Morus/química , Folhas de Planta/química , Proteínas ras/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Gota/tratamento farmacológico , Gota/metabolismo , Supressores da Gota/química , Supressores da Gota/toxicidade , Humanos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , gama-Tocoferol/análise , gama-Tocoferol/farmacologia
18.
Eye Contact Lens ; 47(12): 647-650, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34417788

RESUMO

OBJECTIVES: The aim of this study was to evaluate the tear functions and conjunctival impression cytology (CIC) findings of patients with gout and compare them with healthy controls. METHODS: Thirty-four patients with gout (group 1) and 32 age-matched and gender-matched healthy individuals (group 2) were included in this cross-sectional study. Schirmer 1 test, tear breakup time (TBUT), Ocular Surface Disease Index (OSDI) score, and CIC grade were evaluated and compared between the groups. RESULTS: There was no significant difference between the groups in gender and age (P=0.923 and P=0.078, respectively). The mean of Schirmer 1 test result was significantly lower in group 1 (9.74±6.03 mm) than that in group 2 (17.16±9.33 mm) (P<0.001). The TBUT was also significantly lower in group 1 (7.00±2.09 seconds) than that in group 2 (12.75±5.25 seconds) (P<0.001). The OSDI score (20.04±12.92) was significantly higher in group 1 than that in group 2 (6.19±10.07) (P<0.001). Although 10 patients (29.4%) in group 1 had the CIC grade of 2 to 3, none of the controls had CIC grade 2 to 3. The mean CIC grade in group 1 (1.15±0.89) was significantly higher than that in group 2 (0.47±0.51) (P<0.001). CONCLUSIONS: The results of this study suggest that ocular surface alterations assessed by CIC and tear function abnormalities are more common in patients with gout.


Assuntos
Síndromes do Olho Seco , Gota , Túnica Conjuntiva , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Humanos , Estudos Prospectivos , Lágrimas
19.
Cochrane Database Syst Rev ; 8: CD006190, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34438469

RESUMO

BACKGROUND: This is an updated Cochrane Review, first published in 2006 and updated in 2014. Gout is one of the most common rheumatic diseases worldwide. Despite the use of colchicine as one of the first-line therapies for the treatment of acute gout, evidence for its benefits and harms is relatively limited. OBJECTIVES: To update the available evidence of the benefits and harms of colchicine for the treatment of acute gout. SEARCH METHODS: We updated the search of CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICTRP registries to 28 August 2020. We did not impose any date or language restrictions in the search. SELECTION CRITERIA: We considered published randomised controlled trials (RCTs) and quasi-randomised controlled trials (quasi-RCTs) evaluating colchicine therapy compared with another therapy (placebo or active) in acute gout; low-dose colchicine at clinically relevant doses compared with placebo was the primary comparison. The major outcomes were pain, participant global assessment of treatment success (proportion with 50% or greater decrease in pain from baseline up to 32 to 36 hours), reduction of inflammation, function of target joint, serious adverse events, total adverse events and withdrawals due to adverse events. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane in this review update. MAIN RESULTS: We included four trials (803 randomised participants), including two new trials, in this updated review. One three-arm trial compared high-dose colchicine (52 participants), low-dose colchicine (74 participants) and placebo (59 participants); one trial compared high-dose colchicine with placebo (43 participants); one trial compared low-dose colchicine with non-steroidal anti-inflammatory drugs (NSAIDs) (399 participants); and one trial compared low-dose colchicine with Chuanhu anti-gout mixture (traditional Chinese Medicine compound) (176 participants). We did not identify any trials comparing colchicine to glucocorticoids (by any route). The mean age of participants ranged from 51.2 to 70 years, and trial duration from 48 hours to 12 weeks. Two trials were at low risk of bias, one was possibly susceptible to selection bias (random sequence generation), reporting bias and other bias, and one open-label trial was at high risk of performance and detection bias. For the primary comparison, low-quality evidence from one trial (103 participants, downgraded for imprecision and bias) suggests low-dose colchicine may improve treatment outcome compared to placebo with little or no increased risk of adverse events. The number of people who reported treatment success (50% or greater pain reduction) at 32 to 36 hours was slightly larger with low-dose colchicine (418 per 1000) compared with placebo (172 per 1000; risk ratio (RR) 2.43, 95% confidence interval (CI) 1.05 to 5.64; absolute improvement 25% more reported success (7% more to 42% more, the 95% CIs include both a clinically important and unimportant benefit); relative change of 143% more people reported treatment success (5% more to 464% more). The incidence of total adverse events was 364 per 1000 with low-dose colchicine compared with 276 per 1000 with placebo: RR 1.32, 95% CI 0.68 to 2.56; absolute difference 9% more events with low-dose colchicine (9% fewer to 43% more, the 95% CIs include both a clinically important effect and no effect); relative change of 32% more events (32% fewer to 156% more). No participants withdrew due to adverse events or reported any serious adverse events. Pain, inflammation and function were not reported. Low-quality evidence (downgraded for imprecision and bias) from two trials (124 participants) suggests that high-dose colchicine compared to placebo may improve symptoms, but with increased risk of harms. More participants reported treatment success at 32 to 36 hours with high-dose colchicine (518 per 1000) compared with placebo (240 per 1000): RR 2.16, 95% CI 1.28 to 3.65, absolute improvement 28% (8% more to 46% more); more also had reduced inflammation at this time point with high-dose colchicine (504 per 1000) compared with placebo (48 per 1000): RR 10.50, 95% CI 1.48 to 74.38; absolute improvement 45% greater (22% greater to 68% greater); but more adverse events were reported with high-dose colchicine (829 per 1000 compared with 260 per 1000): RR 3.21, 95% CI 2.01 to 5.11, absolute difference 57% (26% more to 74% more). Pain and function were not reported. Low-quality evidence from a single trial comparing high-dose to low-dose colchicine indicates there may be little or no difference in benefit in terms of treatment success at 32 to 36 hours but more adverse events associated with the higher dose. Similarly, low-quality evidence from a single trial indicates there may also be little or no benefit of low-dose colchicine over NSAIDs in terms of treatment success and pain reduction at seven days, with a similar number of adverse events reported at four weeks follow-up. Reduction of inflammation, function of target joint and withdrawals due to adverse events were not reported in either of these trials, and pain was not reported in the high-dose versus low-dose colchicine trial. We were unable to estimate the risk of serious adverse events for most comparisons as there were few events reported in the trials. One trial (399 participants) reported three serious adverse (one in a participant receiving low-dose colchicine and two in participants receiving NSAIDs), due to reasons unrelated to the trial (low-quality evidence downgraded for bias and imprecision). AUTHORS' CONCLUSIONS: We found low-quality evidence that low-dose colchicine may be an effective treatment for acute gout when compared to placebo and low-quality evidence that its benefits may be similar to NSAIDs. We downgraded the evidence for bias and imprecision. While both high- and low-dose colchicine improve pain when compared to placebo, low-quality evidence suggests that high-dose (but not low-dose) colchicine may increase the number of adverse events compared to placebo, while low-quality evidence indicates that the number of adverse events may be similar with low-dose colchicine and NSAIDs. Further trials comparing colchicine to placebo or other treatment will likely have an important impact on our confidence in the effect estimates and may change the conclusions of this review. There are no trials reporting the effect of colchicine in populations with comorbidities or in comparison with other commonly used treatments, such as glucocorticoids.


Assuntos
Colchicina , Gota , Anti-Inflamatórios não Esteroides/efeitos adversos , Pré-Escolar , Colchicina/efeitos adversos , Glucocorticoides/uso terapêutico , Gota/tratamento farmacológico , Humanos , Lactente , Dor/tratamento farmacológico
20.
Nutrients ; 13(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34444833

RESUMO

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.


Assuntos
Terapia Comportamental , Metformina/uso terapêutico , Ácido Úrico/sangue , Perda de Peso , Idoso , Índice de Massa Corporal , Feminino , Gota , Humanos , Masculino , Maryland , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico
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