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Arthritis Care & Research Jun 2020To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and...
OBJECTIVE
To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.
METHODS
Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.
RESULTS
Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.
CONCLUSION
Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.
Topics: Disease Management; Gout; Healthy Lifestyle; Humans; Symptom Flare Up; Uricosuric Agents
PubMed: 32391934
DOI: 10.1002/acr.24180 -
The Saudi Dental Journal Nov 2021Endodontic treatment corresponds to a combined chemical and mechanical approach, followed by a three dimensional hermetic obturation, that eliminate the pulpal and... (Review)
Review
Endodontic treatment corresponds to a combined chemical and mechanical approach, followed by a three dimensional hermetic obturation, that eliminate the pulpal and periradiculare disease and boost healing and repair of periradiculare tissue. Despite the advances in the endodontic field, the inter-appointment flare up remains a true nightmare that encounters every dentist. This complication commences a few hours or days after root canal procedures and it is characterized by the development of pain and/or swelling, requiring an unscheduled appointment for emergency treatment. Different studies showed that flare-ups represent a multifactorial phenomenon including mechanical, chemical and microbial factors. In addition, a correlation was found between flare-up and age, gender, tooth type, presence of preoperative pain, tooth condition before treatment, irrigation techniques, number of visits as well as intracanal medication. Moreover, some medicine intake was proved to be efficient in controlling this postoperative pain. However, a clear procedure to avoid its occurrence is yet to be established. In this review, we summarize knowledge about the etiology of flare-up and its related factors. This could be effective in helping dentists to adapt some strategies to prevent it.
PubMed: 34803278
DOI: 10.1016/j.sdentj.2021.05.005 -
Stomatologija 2014Flare-ups can occur after root canal treatment and consist of acute exacerbations of an asymptomatic pulpal and/or periradicular pathologic condition. The causative... (Review)
Review
Flare-ups can occur after root canal treatment and consist of acute exacerbations of an asymptomatic pulpal and/or periradicular pathologic condition. The causative factors of interappointment pain encompass mechanical, chemical, and/or microbial injury to the pulp or periradicular tissues. Microorganisms can participate in causation of interappointment pain in the following situations: apical extrusion of debris; incomplete instrumentation leading to changes in the endodontic microbiota or in environmental conditions; and secondary intraradicular infections. Interappointment pain is almost exclusively due to the development of acute inflammation at the periradicular tissues in response to an increase in the intensity of injury coming from the root canal system. The mechanical irritation of apical periodontal tissue is caused by overinstrumentation of the root canal and filling material extrusion through the apical foramen. Incorrectly measured working length of the root canal has inherent connection with these causative factors of endodontic flare - up. This review article discusses these many facets of the flare-up: definition, incidence causes and predisposing factors.
Topics: Dental Pulp Cavity; Humans; Pain, Postoperative; Periapical Diseases; Periapical Tissue; Recurrence; Risk Factors; Root Canal Preparation; Root Canal Therapy; Toothache
PubMed: 24824057
DOI: No ID Found -
Rheumatic Diseases Clinics of North... Nov 2022Gout is the most prevalent type of inflammatory arthritis worldwide and environmental factors contribute to hyperuricemia and risk for gout flare. Causes of... (Review)
Review
Gout is the most prevalent type of inflammatory arthritis worldwide and environmental factors contribute to hyperuricemia and risk for gout flare. Causes of hyperuricemia include increased purine consumption from meat, alcohol, and high fructose corn syrup as well as medications such as cyclosporine, low-dose aspirin, or diuretics. Triggers for gout flares include increased purine consumption and medication use such as urate lowering therapy and diuretics. Environmental exposures including lead exposure, particulate matter exposure, temperature fluctuations, and physiologic stress have been found to trigger flares. In the right clinical scenario, these factors should be considered when treating gout patients.
Topics: Humans; Gout; Hyperuricemia; Symptom Flare Up; Purines; Diuretics; Gout Suppressants
PubMed: 36333002
DOI: 10.1016/j.rdc.2022.06.009 -
JAMA Aug 2022Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated. (Observational Study)
Observational Study
IMPORTANCE
Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated.
OBJECTIVE
To investigate whether there is a transient increase in risk of cardiovascular events after a recent gout flare.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective observational study was conducted using electronic health records from the Clinical Practice Research Datalink in England between January 1, 1997, and December 31, 2020. A multivariable nested case-control study was performed among 62 574 patients with gout, and a self-controlled case series, adjusted for season and age, was performed among 1421 patients with gout flare and cardiovascular event.
EXPOSURES
Gout flares were ascertained using hospitalization, primary care outpatient, and prescription records.
MAIN OUTCOMES AND MEASURES
The primary outcome was a cardiovascular event, defined as an acute myocardial infarction or stroke. Association with recent prior gout flares was measured using adjusted odds ratios (ORs) with 95% CIs in a nested case-control study and adjusted incidence rate ratios (IRRs) with 95% CIs in a self-controlled case series.
RESULTS
Among patients with a new diagnosis of gout (mean age, 76.5 years; 69.3% men, 30.7% women), 10 475 patients with subsequent cardiovascular events were matched with 52 099 patients without cardiovascular events. Patients with cardiovascular events, compared with those who did not have cardiovascular events, had significantly higher odds of gout flare within the prior 0 to 60 days (204/10 475 [2.0%] vs 743/52 099 [1.4%]; adjusted OR, 1.93 [95% CI, 1.57-2.38]) and within the prior 61 to 120 days (170/10 475 [1.6%] vs 628/52 099 [1.2%]; adjusted OR, 1.57 [95% CI, 1.26-1.96]). There was no significant difference in the odds of gout flare within the prior 121 to 180 days (148/10 475 [1.4%] vs 662/52 099 [1.3%]; adjusted OR, 1.06 [95% CI, 0.84-1.34]). In the self-controlled case series (N = 1421), cardiovascular event rates per 1000 person-days were 2.49 (95% CI, 2.16-2.82) within days 0 to 60; 2.16 (95% CI, 1.85-2.47) within days 61 to 120; and 1.70 (95% CI, 1.42-1.98) within days 121 to 180 after a gout flare, compared with cardiovascular event rates of 1.32 (95% CI, 1.23-1.41) per 1000 person-days within the 150 days before or the 181 to 540 days after the gout flare. Compared with 150 days before or the 181 to 540 days after a gout flare, incidence rate differences for cardiovascular events were 1.17 (95% CI, 0.83-1.52) per 1000 person-days, and adjusted IRRs were 1.89 (95% CI, 1.54-2.30) within days 0 to 60; 0.84 (95% CI, 0.52-1.17) per 1000 person-days and 1.64 (95% CI, 1.45-1.86) within days 61 to 120; and 0.38 (95% CI, 0.09-0.67) per 1000 person-days and 1.29 (95% CI, 1.02-1.64) within days 121 to 180 after a gout flare.
CONCLUSIONS AND RELEVANCE
Among individuals with gout, those who experienced a cardiovascular event, compared with those who did not experience such an event, had significantly higher odds of a recent gout flare in the preceding days. These findings suggest gout flares are associated with a transient increase in cardiovascular events following the flare.
Topics: Aged; Cardiovascular Diseases; Case-Control Studies; Electronic Health Records; England; Female; Gout; Humans; Male; Myocardial Infarction; Retrospective Studies; Risk Factors; Stroke; Symptom Flare Up
PubMed: 35916846
DOI: 10.1001/jama.2022.11390 -
The New England Journal of Medicine May 2018Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares.
METHODS
We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab.
RESULTS
At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P<0.001), 35% versus 6% of those with mevalonate kinase deficiency (P=0.003), and 45% versus 8% of those with TRAPS (P=0.006). The inclusion of patients whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71% of those with colchicine-resistant familial Mediterranean fever, 57% of those with mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended dosing regimen (every 8 weeks) maintained disease control in 46% of patients with colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase deficiency, and 53% of those with TRAPS. Among patients who received canakinumab, the most frequently reported adverse events were infections (173.3, 313.5, and 148.0 per 100 patient-years among patients with colchicine-resistant familial Mediterranean fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively), with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years).
CONCLUSIONS
In this trial, canakinumab was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and TRAPS. (Funded by Novartis; CLUSTER ClinicalTrials.gov number, NCT02059291 .).
Topics: Adolescent; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Familial Mediterranean Fever; Female; Fever; Hereditary Autoinflammatory Diseases; Humans; Injections, Subcutaneous; Interleukin-1beta; Male; Mevalonate Kinase Deficiency; Young Adult
PubMed: 29768139
DOI: 10.1056/NEJMoa1706314 -
The Cochrane Database of Systematic... Feb 2017Eczema is a chronic skin disease characterised by dry skin, intense itching, inflammatory skin lesions, and a considerable impact on quality of life. Moisturisation is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eczema is a chronic skin disease characterised by dry skin, intense itching, inflammatory skin lesions, and a considerable impact on quality of life. Moisturisation is an integral part of treatment, but it is unclear if moisturisers are effective.
OBJECTIVES
To assess the effects of moisturisers for eczema.
SEARCH METHODS
We searched the following databases to December 2015: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, the GREAT database. We searched five trials registers and checked references of included and excluded studies for further relevant trials.
SELECTION CRITERIA
Randomised controlled trials in people with eczema.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 77 studies (6603 participants, mean age: 18.6 years, mean duration: 6.7 weeks). We assessed 36 studies as at a high risk of bias, 34 at unclear risk, and seven at low risk. Twenty-four studies assessed our primary outcome 'participant-assessed disease severity', 13 assessed 'satisfaction', and 41 assessed 'adverse events'. Secondary outcomes included investigator-assessed disease severity (addressed in 65 studies), skin barrier function (29), flare prevention (16), quality of life (10), and corticosteroid use (eight). Adverse events reporting was limited (smarting, stinging, pruritus, erythema, folliculitis).Six studies evaluated moisturiser versus no moisturiser. 'Participant-assessed disease severity' and 'satisfaction' were not assessed. Moisturiser use yielded lower SCORAD than no moisturiser (three studies, 276 participants, mean difference (MD) -2.42, 95% confidence interval (CI) -4.55 to -0.28), but the minimal important difference (MID) (8.7) was unmet. There were fewer flares with moisturisers (two studies, 87 participants, RR 0.40, 95% CI 0.23 to 0.70), time to flare was prolonged (median: 180 versus 30 days), and less topical corticosteroids were needed (two studies, 222 participants, MD -9.30 g, 95% CI -15.3 to -3.27). There was no statistically significant difference in adverse events (one study, 173 participants, risk ratio (RR) 15.34, 95% CI 0.90 to 261.64). Evidence for these outcomes was low quality.With Atopiclair (three studies), 174/232 participants experienced improvement in participant-assessed disease severity versus 27/158 allocated to vehicle (RR 4.51, 95% CI 2.19 to 9.29). Atopiclair decreased itching (four studies, 396 participants, MD -2.65, 95% CI -4.21 to -1.09) and achieved more frequent satisfaction (two studies, 248 participants, RR 2.14, 95% CI 1.58 to 2.89), fewer flares (three studies, 397 participants, RR 0.18, 95% CI 0.11 to 0.31), and lower EASI (four studies, 426 participants, MD -4.0, 95% CI -5.42 to -2.57), but MID (6.6) was unmet. The number of participants reporting adverse events was not statistically different (four studies, 430 participants, RR 1.03, 95% CI 0.79 to 1.33). Evidence for these outcomes was moderate quality.Participants reported skin improvement more frequently with urea-containing cream than placebo (one study, 129 participants, RR 1.28, 95% CI 1.06 to 1.53; low-quality evidence), with equal satisfaction between the two groups (one study, 38 participants, low-quality evidence). Urea-containing cream improved dryness (investigator-assessed) more frequently (one study, 128 participants, RR 1.40, 95% CI 1.14 to 1.71; moderate-quality evidence) with fewer flares (one study, 44 participants, RR 0.47, 95% CI 0.24 to 0.92; low-quality evidence), but more participants in this group reported adverse events (one study, 129 participants, RR 1.65, 95% CI 1.16 to 2.34; moderate-quality evidence).Three studies assessed glycerol-containing moisturiser versus vehicle or placebo. More participants in the glycerol group noticed skin improvement (one study, 134 participants, RR 1.22, 95% CI 1.01 to 1.48; moderate-quality evidence), and this group saw improved investigator-assessed SCORAD (one study, 249 participants, MD -2.20, 95% CI -3.44 to -0.96; high-quality evidence), but MID was unmet. Participant satisfaction was not addressed. The number of participants reporting adverse events was not statistically significant (two studies, 385 participants, RR 0.90, 95% CI 0.68 to 1.19; moderate-quality evidence).Four studies investigated oat-containing moisturisers versus no treatment or vehicle. No significant differences between groups were reported for participant-assessed disease severity (one study, 50 participants, RR 1.11, 95% CI 0.84 to 1.46; low-quality evidence), satisfaction (one study, 50 participants, RR 1.06, 95% CI 0.74 to 1.52; very low-quality evidence), and investigator-assessed disease severity (three studies, 272 participants, standardised mean difference (SMD) -0.23, 95% CI -0.66 to 0.21; low-quality evidence). In the oat group, there were fewer flares (one study, 43 participants, RR 0.31, 95% CI 0.12 to 0.7; low-quality evidence) and less topical corticosteroids needed (two studies, 222 participants, MD -9.30g, 95% CI 15.3 to -3.27; low-quality evidence), but more adverse events were reported (one study, 173 participants; Peto odds ratio (OR) 7.26, 95% CI 1.76 to 29.92; low-quality evidence).All moisturisers above were compared to placebo, vehicle, or no moisturiser. Participants considered moisturisers more effective in reducing eczema (five studies, 572 participants, RR 2.46, 95% CI 1.16 to 5.23; low-quality evidence) and itch (seven studies, 749 participants, SMD -1.10, 95% CI -1.83 to -0.38) than control. Participants in both treatment arms reported comparable satisfaction (three studies, 296 participants, RR 1.35, 95% CI 0.77 to 2.26; low-quality evidence). Moisturisers led to lower investigator-assessed disease severity (12 studies, 1281 participants, SMD -1.04, 95% CI -1.57 to -0.51; high-quality evidence) and fewer flares (six studies, 607 participants, RR 0.33, 95% CI 0.17 to 0.62; moderate-quality evidence), but there was no difference in adverse events (10 studies, 1275 participants, RR 1.03, 95% CI 0.82 to 1.30; moderate-quality evidence).Topical active treatment combined with moisturiser was more effective than active treatment alone in reducing investigator-assessed disease severity (three studies, 192 participants, SMD -0.87, 95% CI -1.17 to -0.57; moderate-quality evidence) and flares (one study, 105 participants, RR 0.43, 95% CI 0.20 to 0.93), and was preferred by participants (both low-quality evidence). There was no statistically significant difference in number of adverse events (one study, 125 participants, RR 0.39, 95% CI 0.13 to 1.19; very low-quality evidence). Participant-assessed disease severity was not addressed.
AUTHORS' CONCLUSIONS
Most moisturisers showed some beneficial effects, producing better results when used with active treatment, prolonging time to flare, and reducing the number of flares and amount of topical corticosteroids needed to achieve similar reductions in eczema severity. We did not find reliable evidence that one moisturiser is better than another.
Topics: Adrenal Cortex Hormones; Eczema; Emollients; Humans; Patient Satisfaction; Randomized Controlled Trials as Topic; Severity of Illness Index; Symptom Flare Up
PubMed: 28166390
DOI: 10.1002/14651858.CD012119.pub2 -
Viruses Feb 2022Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB)... (Review)
Review
Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. Currently, pegylated interferon (Peg-IFN), entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line drugs of choice. Peg-IFN therapy has been used rarely due to its subcutaneous injection and significant side effect profile. Once daily oral ETV, TDF and TAF can suppress HBV DNA profoundly but have no direct action on cccDNA of the HBV-infected hepatocytes, hence continuing long-term therapy is usually needed to maintain HBV suppression, but the ultimate goal of HBsAg loss was rarely achieved (10 year 2%). In addition, long-term NUC therapy comes with several concerns such as increasing cost, medication adherence and loss-to-follow-up. Studies, mainly from Taiwan, have shown that finite NUCs therapy of two to three years in HBeAg-negative patients is feasible, safe and has a great benefit of much increasing HBsAg loss rate up to 30%/5 year. These have led an emerging paradigm shift to finite NUC therapy in HBeAg-negative patients globally. However, off-NUC relapse with hepatitis B flares may occur and have a risk of decompensation or even life-threatening outcomes. Therefore, proper monitoring, assessment, and retreatment decisions are crucial to ensure safety. Ideally, retreatment should be not too late to ensure safety and also not too early to allow further immune response for further HBsAg decline toward HBsAg loss. Assessment using combined HBsAg/ALT kinetics during hepatitis flare is better than biochemical markers alone to make a right retreatment decision. The strategy of finite NUC therapy has set a benchmark of high HBsAg loss rate to be achieved by the new anti-HBV drugs which are under preclinical or early phase study.
Topics: Antiviral Agents; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Nucleosides; Nucleotides; Randomized Controlled Trials as Topic; Symptom Flare Up; Tenofovir; Treatment Outcome
PubMed: 35216027
DOI: 10.3390/v14020434 -
Seminars in Arthritis and Rheumatism Jun 2020Gout is a disease in which the metabolic condition hyperuricemia leads to the formation of monosodium urate crystals, which provoke acute and chronic inflammatory... (Review)
Review
Gout is a disease in which the metabolic condition hyperuricemia leads to the formation of monosodium urate crystals, which provoke acute and chronic inflammatory responses through activation of the innate immune system. Recent advances in our knowledge of gout pathogenesis have emphasized the role of the kidneys in urate handling, the evolutionary loss of uricase as a necessary precondition for hyperuricemia, and the central role of IL-1ß in the pathogenesis of gouty inflammation. These, and other advances, have shaped our current strategies for managing gout. Here, we review the most current, evidence-based gout management approaches, including treating acute flares, addressing gout through the long-term regulation of serum urate, and prophylaxis against gouty flares during urate lowering.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Symptom Flare Up; Uric Acid
PubMed: 32620199
DOI: 10.1016/j.semarthrit.2020.04.010 -
American Journal of Clinical Dermatology Jan 2022Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by episodes of widespread sterile macroscopic pustules, with or... (Review)
Review
Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by episodes of widespread sterile macroscopic pustules, with or without systemic inflammation and/or plaque psoriasis. Multiple GPP subtypes have been described, from acute GPP of von Zumbusch to milder, annular pustular psoriasis. Generalized pustular psoriasis mainly affects adults, with a female preponderance, but juvenile GPP also occurs. Flares are a hallmark of GPP and may occur de novo or be provoked by triggers, including withdrawal of systemic corticosteroids, infections, stress, pregnancy, and menstruation. Severity of flares varies widely between patients, and between flares in an individual patient. Significant flares are often accompanied by systemic symptoms, notably fever, general malaise, and extracutaneous manifestations such as arthritis, uveitis, and neutrophilic cholangitis. Common laboratory abnormalities include neutrophilia, elevated C-reactive protein levels, hypocalcemia, and abnormal liver function tests. The clinical course of GPP is highly variable; it can be a relapsing disease with recurrent flares and no pustulation between flares or a persistent disease with perpetual mild pustulation punctuated with flares of greater severity. Patients may have multiple flares per year or a flare every few years. Most flares last 2-5 weeks and approximately 50% require hospitalization. Life-threatening complications include sepsis and renal, hepatic, respiratory, and heart failure. Reported mortality rates are 2-16%.
Topics: Disease Progression; Humans; Psoriasis; Skin Diseases, Vesiculobullous; Symptom Flare Up
PubMed: 35061227
DOI: 10.1007/s40257-021-00654-z