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Younger age of onset of gout in Taiwan.

OBJECTIVE: To study the clinical features of gout in the community and in medical centres, and to describe the recent changes in gout in Chinese patients. METHODS: We analysed retrospectively the clinical features of 1079 Chinese gout patients seen by a rheumatologist between 1993 and 2000. These included 558 patients from a private clinic and 521 patients from a medical centre. The data were compared with those in previous reports of large Caucasian and non-Caucasian series. RESULTS: The mean age of onset was 41.6 yr and the mean disease duration before first visit was 4.2 yr. For medical centre patients, the mean age of onset was 43.0 yr and mean disease duration before the first visit was 4.8 yr. For private clinic patients, the mean age of onset was 40.2 yr and mean disease duration before the first visit was 3.6 yr. Young patients with gout, with onset before age 30, constituted 23.3 and 26.7% of the medical centre and private clinic patients respectively. Female patients constituted 10.6 and 5.6% respectively, the family history was positive in 27.1 and 28.7%, and urolithiasis occurred in 11.5 and 10.9%. Tophi were found in 21.1% of medical centre and 12.7% of private clinic patients. The mean time from first gouty attack to visible tophi was 6.6 yr in those who developed tophi. CONCLUSIONS: The age at onset of gout was much earlier than in previous reports. Twenty-five per cent of patients had their first gouty attack before age 30. The first attack frequently occurred between the third and fifth decades (68.2%) rather than between the fourth and sixth decades, as reported in previous papers. The incidence of gout in females had increased (8.0% of the patients were female) and the incidence of tophi was high (16.8%). Besides, our patients had more frequent gouty attacks and the interval from the first attack to visible tophi was shorter than in previous reports of the disease in Caucasians.

Adult↗

Gout and hyperuricemia.

Although our understanding of hyperuricemia and gout has changed little over the past several years, questions remain in defining the many metabolic abnormalities that can result in these problems. In the past year, several papers have further addressed heritable mechanisms for the development of hyperuricemia, as well as environmental factors that contribute to its onset in adulthood. Consequences of hyperuricemia other than clinical gout have received further attention. Although typical gout is easily recognized and treated, several recent papers have addressed atypical presentations of gout, as well as other causes of podagra that might have been attributed previously to gout. The treatment of patients whose disease is uncomplicated by other conditions remains straightforward. However, the presentation of gout in patients with multiple comorbidities not only increases recognition of the toxicity of nonsteroidal anti-inflammatory drugs and colchicine, but often requires innovative approaches to its treatment.

Adult↗

Gout and hyperuricemia.

Gout continues to be a health problem around the world despite the availability of effective therapies. Although the prevalence is influenced by genetic factors, the associations of alcohol consumption, obesity, and hypertension appear to be partially responsible for the increased prevalence of gout and hyperuricemia in African and Oriental countries. The association between hyperuricemia and cardiovascular disease seems linked to insulin resistance. This relation, in part, explains the common coexistence of hyperlipidemia and glucose intolerance in patients with gout. Accordingly, it is recommended that one pay more attention to dietary manipulation in patients with gout in addition to managing hypertension, obesity, and other medical problems. Although acute gout attacks can be treated, eliminating gout requires effective removal of urate from the body. Allopurinol remains a dominant urate-lowering agent, however its use may be limited by allergic reactions. Uricosuric agents are also effective urate-lowering agents and provide an alternative to allopurinol. Strategies to treat patients who are sensitive to allopurinol continue to evolve.

Africa↗

Recent developments in diet and gout.

PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men, affecting approximately 1-2% of adult men in Western countries. United States gout prevalence has approximately doubled over the past two decades. In recent years, key prospective epidemiological and open-labeled dietary studies, coupled with recent advances in molecular biology elucidating proximal tubular urate transport, have provided novel insights into roles of diet and alcohol in hyperuricemia and gout. This review focuses on recent developments and their implications for clinical practice, including how we advise patients on appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies have observed an increased risk of gout among those who consumed the highest quintile of meat, seafood and alcohol. Although limited by confounding variables, low-fat dairy products, ascorbic acid and wine consumption appeared to be protective for the development of gout. SUMMARY: The most effective forms of dietary regimen for both hyperuricemia and gout flares remains to be unidentified. Until confirmed by a large, controlled study, it is prudent to advise patients to consume meat, seafood and alcoholic beverages in moderation, with special attention to food portion size and content of non-complex carbohydrates which are essential for weight loss and improved insulin sensitivity.

Beer↗

Gout Assessment Questionnaire: Initial results of reliability, validity and responsiveness.

We evaluated the psychometric properties of a new gout-specific patient reported outcomes questionnaire. The Gout Assessment Questionnaire (GAQ) and the SF-36 were administered to 126 subjects in a multicenter Phase II program of febuxostat, an investigational treatment for hyperuricemia (serum uric acid >8.0 mg/dl) in patients with chronic gout. The questionnaire was administered at baseline and 1, 6 and 12 months later. The majority of subjects, mean age 54 years, were male, Caucasian and had experienced a gout flare within the last year. Seven domains were identified, all met criteria for reliability and validity. Cronbach's alpha ranged from 0.78 to 0.97. Pearson correlations between GAQ and SF-36 scales were generally low to moderate, with the highest correlation between Gout Pain and Severity and SF-36 Bodily Pain, r = 0.45. Guyatt's statistic (measure of responsiveness) ranged from 0.24 to 1.00 at 12 months. Minimal clinically important differences ranged from 2 (Gout Concern) to 10 points (Productivity). The GAQ has acceptable psychometric properties. Further research is required to confirm results, which may provide more information to improve the GAQ for use in clinical trials.

Adult↗

Frequency of chondrocalcinosis of the knees and avascular necrosis of the femoral heads in gout: a controlled study.

An association between urate gout and chondrocalcinosis has been suggested in several studies, but the situation remains ill-defined because of lack of appropriate controls, small numbers of patients studied, or retrospective investigation. An association has also been claimed between gout and avascular necrosis of the femoral head. 138 patients with gout and 142 non-gouty control subjects were carefully matched for age and x-rays were taken of the knees and pelvis. Chondrocalcinosis of the knees was detected in 8 patients with gout (5.8%), no cases being found in the control group. The difference is significant (P less than 0.025). Deposits were linear or irregular. Six of the 8 patients gave a history of acute synovitis of the knees; fluid had been aspirated in 2 of them, urate crystals being found in one and no crystals in the other. Six of 8 patients showed evidence of chondrocalcinosis elsewhere. No association was apparent between chondrocalcinosis and the presence of tophaceous deposits or renal impairment, though the duration of gout appeared to be longer in the patients with chondrocalcinosis than in the other gout patients and osteoarthrosis of the knees commoner. There was no evidence of other metabolic disorders commonly associated with chondrocalcinosis. No cases of avascular necrosis of the femoral head were found.

Adult↗

Hyperlipoproteinaemia in primary gout: hyperlipoproteinaemic phenotype and influence of alcohol intake and obesity in Japan.

Serum lipoprotein profiles were investigated in 108 male patients with primary gout before treatment to elucidate the prevalence of each individual phenotype of coexisting hyperlipoproteinaemia and pathogenic factors responsible for it. The mean serum triglyceride (TG) and total cholesterol (TC) levels in the patients with gout were 2.10 +/- 0.14 mmol/l and 5.26 +/- 0.10 mmol/l (mean +/- SEM) respectively, which were significantly higher (p less than 0.01 and p less than 0.05 respectively) than the levels in age matched controls without gout (1.30 +/- 0.07 mmol/l and 4.77 +/- 0.08 mmol/l respectively). Serum high density lipoprotein cholesterol (HDL-C) values were slightly decreased in patients with gout compared with controls (1.24 +/- 0.08 mmol/l v 1.40 +/- 0.03 mmol/l, p less than 0.05). Hyperlipoproteinaemia was seen in 61 patients (56%), of whom patients with type IIa, IIb, and IV hyperlipoproteinaemia formed 13, 15, and 69% respectively. Thus the prevalence of type IV hyperlipoproteinaemia was high in primary gout as compared with primary hyperlipoproteinaemia with primary hyperlipoproteinaemia (69% v 43%, p less than 0.01). The independent and relative influences of clinical data of the patients upon the concentrations of serum lipids were assessed by stepwise multiple regression analysis. Two major predictors of serum TG level were alcohol intake (p less than 0.01) and serum uric acid level (p less than 0.05). The most significant predictive variable was alcohol intake, but its influence was judged to be small (r2 = 0.067). None of the other variables, including obesity index, had any significant influence. The relationships between any of these variables and serum TC or HDL-C levels were not significant. In addition, serum lipid levels were investigated in patients with neither obesity (defined as 120% or more of ideal body weight) nor a history of alcohol intake. Their serum TG and TC concentrations were also significantly higher than the respective control levels. Thus hyperlipoproteinaemia in primary gout its unlikely to be secondary to excess alcohol intake or obesity, or both. Instead, it may result from genetic factors such as a combined hyperlipidaemic trait.

Adult↗

From genetic causality to druggable targets: A multiomics framework identifies ZSCAN16 in gout pathogenesis.

ObjectiveGout is a prevalent form of inflammatory arthritis in which many patients respond suboptimally to current therapies. Drug development is hampered by a lack of genetically validated targets, leading to high clinical trial attrition. This study aimed to systematically identify and prioritize novel, druggable targets for gout via a multilayered genetic and functional genomics approach.MethodsWe performed two-sample Mendelian randomization (MR) using cis-expression quantitative trait locus (cis-eQTL) data and dual independent gout genome-wide association study (GWAS) cohorts (openGWAS and FinnGen). The candidate genes were subjected to a rigorous validation pipeline including Bayesian colocalization, phenome-wide association studies (PheWASs) to assess pleiotropy and on-target safety, and single-cell RNA sequencing (scRNA-seq) to delineate the cellular context. Molecular docking was used to evaluate the structural druggability of prioritized targets.ResultsMR analysis revealed 15 genes causally associated with gout. Colocalization analysis (PPH4 > 0.8) prioritized two targets: ZSCAN16 (risk-increasing, OR = 1.04, 95% CI [1.02-1.06]) and TRIM10 (protective, OR = 0.96, 95% CI [0.94-0.98]). Crucially, PheWAS revealed that ZSCAN16 is highly specific to gout, whereas TRIM10 exhibited extensive pleiotropy with hematological and cardiometabolic traits, indicating significant safety risks. Single-cell analysis provided orthogonal validation, demonstrating flare-specific upregulation of ZSCAN16 in cytotoxic T/NK cells. Molecular docking confirmed ZSCAN16 as a structurally druggable target, showing high-affinity binding with known compounds (e.g. digoxin, binding energy = -9.6 kcal/mol).ConclusionsOur study identifies ZSCAN16 as a high-potential, druggable therapeutic target for gout, highlighting its genetic influence on specific immune cell activities during acute flares. Conversely, TRIM10 was deprioritized owing to substantial pleiotropic liabilities and poor chemical tractability. These findings suggest that ZSCAN16 could play a crucial role in the pathogenesis of gout and may provide a valuable lead for future drug discovery efforts.

Humans↗

Is ritonavir boosting associated with gout?

Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has rarely been reported. We present a retrospective cohort study of 1825 HIV-positive patients seen at one inner London HIV clinic over a two-year period. In all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy. Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy, haematological malignancy). Of the remaining 11 patients, two were on no medication and eight (73%) were receiving ritonavir as a boosted protease inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the 18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was seen in patients with known risk factors for gout or who were receiving ritonavir as a boosted PI and who also had lipodystrophy.

Gout↗

Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, safety profile, precautions, and place in therapy of febuxostat, a novel nonpurine xanthine oxidase inhibitor in development for the treatment of hyperuricemia and gout. DATA SOURCES: Available studies and abstracts were identified through MEDLINE (1990-November 2006), Science Citation Index, International Pharmaceutical Abstracts, Cochrane Databases, and the American College of Rheumatology and European League Against Rheumatism Web sites. Key search terms were febuxostat, TMX-67, TEI-6720, hyperuricemia, and gout. STUDY SELECTION AND DATA EXTRACTION: All available studies describing the pharmacology of febuxostat were included. Human studies formed the basis for discussion of clinical parameters, including pharmacokinetics, pharmacodynamics, efficacy, and safety of febuxostat. DATA SYNTHESIS: Febuxostat significantly reduces uric acid levels within 2 weeks after initiation of therapy and up to 48% by the end of 104 weeks of therapy. Approximately 60% of patients achieved the primary goal of serum uric acid less than 6 mg/dL during the last 3 months following once-daily administration of febuxostat 80 mg or 120 mg for at least 52 weeks. The most common adverse reactions to febuxostat were abnormal results from liver function tests, diarrhea, headache, arthralgias, and musculoskeletal symptoms. Due to its potency, patients are at an increased risk of experiencing gout flares for at least the first year of therapy. Up to 70% of patients in clinical trials experienced gout flares despite concomitant prophylactic treatment with colchicine or naproxen. Additional clinical trial evidence supports the efficacy and safety of febuxostat in the treatment of hyperuricemia and gout. CONCLUSIONS: Febuxostat is a promising alternative to allopurinol for the treatment of gout and hyperuricemia. The optimal length of prophylactic therapy, clinical significance of abnormal liver function tests results during therapy, and safety in patients with moderate or severe renal insufficiency warrant further investigation.

Febuxostat↗

Integrated Network Pharmacology and Molecular Docking Analysis of Sishen Decoction Identifies Potential Targets and Pathways in Gout.

Gout is a disease characterized by hyperuricemia and the deposition of urate crystals in joints and soft tissues, leading to recurrent acute arthritis. Its increasing prevalence imposes substantial clinical and socioeconomic burdens. Sishen Decoction (SSD) has been used in the treatment of gout, but its potential molecular mechanisms remain unclear. This study applied an integrated network pharmacology and molecular docking approach to identify potential targets and signaling pathways associated with SSD in gout. Active compounds and corresponding targets of SSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while gout-related targets were collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Overlapping targets were identified and used to construct a drug-component-target-disease network. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking using the docking server analysis module. A total of 37 bioactive compounds were associated with 116 overlapping gout-related targets. The top hub targets included TP53, IL6, IL1B, TNF, AKT1, EGFR, CASP3, JUN, BCL2, and MMP9. GO analysis suggested that these targets are involved in gene expression regulation and signal transduction. KEGG enrichment analysis indicated significant associations with the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), interleukin-17 (IL-17), and tumor necrosis factor (TNF) signaling pathways. Molecular docking predicted favorable interactions between key compounds and hub targets, with all binding energies of ≤-5 kcal/mol. These computational findings provide potential mechanistic hypotheses for the action of SSD in gout and may support future experimental validation.

Molecular Docking Simulation↗

Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen.

OBJECTIVE: This is a population survey conducted in 1991-92 among residents aged > or =30 years in Kin-Hu, Kinmen, with a 77.7% response rate to study the prevalence of hyperuricemia and hyperuricemia associated gout. A stratified analysis based on sex and age was used to assess the interaction and analyze the associated risk factors for hyperuricemia and gout. METHODS: Hyperuricemia was defined as uric acid > or =7.0 mg/dl for men and > or =6.0 mg/dl for women. Gout was clinically diagnosed by a senior rheumatologist based on patient's history and examination according to the clinical criteria of Wallace. Basic demographic and lifestyle variables as well as biochemical data were collected. RESULTS: The prevalence of hyperuricemia was 25.8% (391/1515) in men and 15.0% (250/1670) in women. The prevalence of gout among hyperuricemic subjects was 11.5% for men and 3% for women. According to age spectrum, the risk factor for hyperuricemia was hyperlipidemia in young adults (30-39 yrs); lifestyle and some clinical syndromes played a significant role in middle aged persons (40-59 yrs). The different risk factors between the sexes in middle age were alcohol consumption effect in men and menopause effect in women. Impaired renal function and use of diuretics became the important factors in the elderly (> or =60 yrs). The risk factors for gout among either the general population or subjects with hyperuricemia were concentration of serum uric acid, alcohol consumption, and central obesity. CONCLUSION: Risk factors for hyperuricemia tended to be different with respect to sex and age. Alcohol consumption and central obesity were independent predictors of gout among hyperuricemic subjects irrespective of uric acid level.

Adult↗

A survey of indications, results and complications of surgery for tophaceous gout.

AIMS: To document the indications, results and complications associated with surgery for tophaceous gout in Middlemore Hospital. METHODS: A retrospective study of the notes of all patients who underwent surgery for tophaceous gout at Middlemore Hospital from July 1995 to July 2001 was performed. Serum creatinine and uric acid results were obtained and the use of allopurinol assessed. RESULTS: 45 patients underwent surgery for gouty tophi. 89% were males and 11% females. 16% were Maori, 38% Pacific people, 42% Europeans and 4% were from other ethnic backgrounds. Renal impairment (serum creatinine. >0.11 mmol/L) was the most common associated medical problem (38%), followed by hypertension (27%), ischaemic heart disease and/or congestive heart disease (20%) and diabetes mellitus (18%). 68% of patients had elevated serum urate levels (>0.42 mmol/L) and only 31% had previously been taking allopurinol. Sepsis control in infected or ulcerated tophi was the main indication for surgery (51%), followed by mechanical problems caused by foot, elbow and hand tophi (27%). The diagnosis of soft tissue masses was unclear in 18% of the patients prior to surgery. 4% of patients underwent tophus surgery mainly for pain control. 53% of patients experienced delayed wound healing as a result of complications of surgery with the majority of these patients (16/24, 67%) having infected or ulcerated tophi prior to surgery. Three patients (7%) required digital amputations for ongoing sepsis. 47% of patients did not have any complication of surgery and had complete wound healing within one week. CONCLUSIONS: Surgery for tophaceous gout is associated with a relatively high rate of complication when sepsis is the main indication. Patients with gout in this study population had several associated medical co-morbidities, which contributed to the high complication rate. Gout control was poor as evidenced by a high rate of hyperuricaemia, and less than one third of the study population were on allopurinol. Better control of gout would reduce the risk of tophi formation and the need for surgery.

Adult↗

[Insulin resistance syndrome in patients with gout and its influence on formation of clinical characteristics of the disease].

AIM: To evaluate the occurrence of immunoresistance (IR) syndrome in gout and its correlation with a gout course. MATERIAL AND METHODS: Anthropometric parameters, blood lipid spectrum, levels of glucose, uric acid (UA), immunoreactive insulin, HOMA index were studied in 55 male patients with gout (mean age 50.1 +/- 7.9 years, mean duration of the disease 7.5 +/- 7.2 years). Statistic processing was made with computer program Statistica 6.0. RESULTS: IR was revealed in 49% patients. Immunoresistant patients had visceral obesity, arterial hypertension, abnormal lipid profile, high UA concentrations, longer disease, chronic articular syndrome, high occurrence of diabetes mellitus and vascular events significantly more frequently. CONCLUSION: IR in gout patients is the risk factor of cardiovascular diseases; combination of IR and hyperinsulinemia is characterized by marked hyperuricemia and a trend to chronic course of the articular syndrome. Longer duration of gout, especially treated inadequately, raises the risk of IR. IR deteriorates prognosis in relation to cardiovascular diseases, diabetes mellitus type 2, course of gout itself.

Adult↗

Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population.

OBJECTIVE: To determine whether the prevalence of gout and/or clinically significant hyperuricemia increased in a managed care population over 10 years. METHODS: The study was a descriptive analysis utilizing an administrative claims database to ascertain 10-year trends in prevalence of gout and/or hyperuricemia. Prevalence rates were calculated cross-sectionally for each year (1990-99) and expressed/compared as rates per 1000 enrollees. RESULTS: The prevalence of gout and/or hyperuricemia in the overall population increased by about 2 cases per 1000 enrollees over 10 years. In the > 75 year age group, rates increased from 21 per 1000 persons in 1990 to 41 per 1000 in 1999. In the 65-74 year age group, prevalence increased from between 21 and 24 per 1000 persons in the years 1990-92 to over 31 per 1000 during the years 1997-99. Prevalence rates in younger age groups (< 65 years) stayed consistently low during the years under study. There were sex differences in most age groups, with men having the greater burden of disease at every time point. CONCLUSION: Prevalence of gout and/or hyperuricemia in the overall study population increased during the 10-year period. When stratified by age, there were increases in prevalence among groups over age 65 in both sexes. Although gout prevalence increased in both sexes over the 10-year period, men still had most of the burden of disease. In ages younger than 65, men had 4 times higher prevalence than women (4:1 ratio), but in the older age groups (> 65), the gender gap narrowed to 1 woman to every 3 men with gout and/or hyperuricemia (3:1 ratio).

Adolescent↗

[Investigation on "gout" and comparison of disorder between Chinese and Western medicine in pre-Song-yuan dynasty].

Before the Song-Yuan dynasties, it was claimed that "gout" is the result of heat in the blood plus invasion of wind, cold, or dampness, leading to coagulation of turbid dampness in the channel-collaterals, characterized by arthralgia, exacerbated in the nighttime. "Gout" was first seen in the Ming yi bie lu (Other Records of Famous Physicians) of the Liang dynasty. Before that, it was categorized under "bi" syndrome. No detailed description was given to "gout" during the period from the first appearance of the title "gout" to the Yuan dynasty. In fact, it was vaguely mentioned in "bi", "li jie", and "bai hu (white tiger)" disorders. The title of "gout" was named by Zhu Danxi, and appeared alternately with gouty arthritis. "li jie" and "bai hu" are titles of two different diseases which were jointly called "lijiebaihu" in the Song dynasty, both similar to gouty arthritis. The TCM title of gout was based on this condition which is specific and very proximate to gouty arthritis.

Arthritis, Gouty↗

Benzbromarone therapy in management of refractory gout.

AIM: To assess the efficacy and safety of benzbromarone in patients with renal impairment and severe tophaceous gout (despite receiving optimal conventional therapy). METHODS: Six patients with refractory gout (despite optimal therapy) were treated with benzbromarone. Uric acid levels and number of gout attacks were recorded monthly. Adverse events to medications were also recorded. RESULTS: After 1 year of treatment with benzbromarone, average uric acid level reduced from 0.61 mmol/L to 0.46 mmol/L. Repeated measures tests on the changes in uric acid were clinically significant (p=0.01). The frequency of acute attacks of gout was reduced from 16 (8-20) to 7.3 (1-16); p=0.01. None of the patients reported adverse events with the medications. There were no acute flares resulting from initiation of medications. CONCLUSION: Benzbromarone is effective in lowering uric acid levels and in reducing the number of acute attacks of gout in patients who have failed optimal treatment. Making this drug more readily available will increase our therapeutic choices for urate reduction and help decrease the morbidity associated with gout.

Adult↗

Gouty arthritis. A primer on late-onset gout.

Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.

Aged↗