-
The Cochrane Database of Systematic... Nov 2019Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC).
OBJECTIVES
The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis.
SEARCH METHODS
We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings.
SELECTION CRITERIA
Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome.
MAIN RESULTS
Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear. Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence). Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation (a probiotic formulation) participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain.
PREVENTION
At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence).
AUTHORS' CONCLUSIONS
The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.
Topics: Anastomosis, Surgical; Anti-Bacterial Agents; Budesonide; Ciprofloxacin; Colitis, Ulcerative; Enema; Gastrointestinal Agents; Humans; Metronidazole; Postoperative Complications; Pouchitis; Probiotics; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 31785173
DOI: 10.1002/14651858.CD001176.pub5 -
BioMed Research International 2019The syndrome of drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with...
BACKGROUND
The syndrome of drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with anticonvulsants, sulfonamides, and allopurinol. The reaction commonly manifests as a febrile skin eruption with lymphadenopathy and malaise between two and eight weeks following drug exposure. Internal organ involvement occurs in close to 90 percent of patients, and multiple organs may be involved in approximately half of those affected (most commonly the liver, kidney, and lung). Its long latency period and its variable clinical pattern of presentation have earned it the moniker of "the great mimicker," with delays in diagnosis leading to higher morbidity and mortality. Although less commonly affected in DRESS syndrome, lung involvement is associated with more severe clinical course and potentially worse outcome. Pulmonary symptoms may precede development of the other more common symptoms and signs of the syndrome, or they might develop later in the course of the disease. Lung involvement in DRESS presents with a plethora of manifestations from mild cough or dyspnea with nonspecific interstitial changes on chest imaging to acute respiratory distress syndrome (ARDS) with life-threatening hypoxic respiratory failure.
METHODS
We performed a systematic review of literature from the PubMed database and selected cases of definite DRESS syndrome as defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) with a score of 6 or more who also had pulmonary involvement. Demographic data, pattern of lung involvement, culprit medication, latency period, laboratory findings, therapy, and outcome were described and compared with the literature.
RESULTS
The most common pulmonary radiographic findings in DRESS were interstitial infiltrates in 50% of cases, followed by acute respiratory distress syndrome (ARDS) 31%. Symptoms of cough and shortness of breath (SOB) were present in 72% of patients at the time of presentation. SOB was the more common presenting symptom (81%) compared to cough (19%). In 95% of cases, another visceral organ was involved (most commonly liver or kidneys). 45% of cases were initially misdiagnosed as pneumonia and were treated with empiric antimicrobials. In a multivariate regression, a latency of 30 days or less and an age of 60 or less were associated with development of ARDS. Gender and eosinophil count were not associated with severity of pulmonary manifestations. All patients recovered, and in the vast majority of cases (95%), parenteral steroids were used for treatment in addition to supportive care and symptomatic management.
CONCLUSION
Albeit rare, DRESS is a potentially life-threatening syndrome which may present with a myriad of pulmonary signs and symptoms. Pulmonary manifestations are less common but are typically seen in more severe cases. Pulmonary manifestations may be a presenting sign of DRESS, and timely recognition is important in order to stop offending medication and decrease morbidity and mortality.
Topics: Drug Hypersensitivity Syndrome; Eosinophilia; Humans; Lung; Pneumonia; Respiratory Distress Syndrome
PubMed: 31662996
DOI: 10.1155/2019/7863815 -
Clinical Nephrology Jan 2020Treatment with allopurinol has been suggested to reduce the incidence of contrast-induced acute kidney injury (CI-AKI). However, results of previous randomized... (Meta-Analysis)
Meta-Analysis
Effects of allopurinol pretreatment on the risk of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials .
BACKGROUND
Treatment with allopurinol has been suggested to reduce the incidence of contrast-induced acute kidney injury (CI-AKI). However, results of previous randomized controlled trials (RCTs) are not consistent. We performed a meta-analysis to evaluate the influence of allopurinol on the risk of CI-AKI.
MATERIALS AND METHODS
Related RCTs were identified via systematic search of electronic databases including PubMed, Embase, and Cochrane's Library. The influence of allopurinol on the incidence of CI-AKI was defined as the primary outcome. Results were pooled using a random-effects model or a fixed-effects model according to the heterogeneity.
RESULTS
Five RCTs with 754 patients who underwent percutaneous coronary intervention (PCI) were included. All patients received preprocedural hydration therapy with intravenous normal saline. Pooled results showed that allopurinol significantly reduced the incidence of CI-AKI (risk ratio (RR): 0.37, p = 0.01). Subgroup analyses demonstrated that allopurinol significantly reduced the incidence of CI-AKI in high-risk patients (incidence of CI-AKI ≥ 30%, RR: 0.10, p = 0.04) but not in low-risk patients (incidence of CI-AKI < 30%, RR: 0.67, p = 0.14). Moreover, allopurinol significantly prevented the increment of serum creatinine (weighted mean difference (WMD): -0.13 mg/dL, p < 0.001) and attenuated the loss of estimated glomerular filtration rate (WMD: 4.78 mL/min, p = 0.04). However, serum uric acids were not significantly affected (WMD: -0.26 mg/dL, p = 0.72).
CONCLUSION
Pretreatment with allopurinol reduces the incidence of CI-AKI in patients undergoing contrast exposure in PCI. The benefits of allopurinol on CI-AKI may be more remarkable in high-risk patients.
Topics: Acute Kidney Injury; Allopurinol; Contrast Media; Coronary Angiography; Creatinine; Enzyme Inhibitors; Glomerular Filtration Rate; Humans; Percutaneous Coronary Intervention; Preoperative Care; Randomized Controlled Trials as Topic; Risk Factors; Uric Acid
PubMed: 31661061
DOI: 10.5414/CN109815 -
The Cochrane Database of Systematic... Oct 2019Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms.... (Review)
Review
BACKGROUND
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. We considered a 25% decrease of NIH-CPSI baseline score or a six-point reduction as MCID.
OBJECTIVES
To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome.
SEARCH METHODS
We performed a comprehensive search using CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, trial registries, grey literature and conference proceedings, with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019.
SELECTION CRITERIA
We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions compared to placebo or in head-to-head comparisons.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, extracted data, and assessed the risks of bias of included studies. We assessed the quality of the evidence (QoE) using the GRADE approach.
MAIN RESULTS
We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Unless stated otherwise, our comparisons were based on short-term follow-up (less than 12 months). Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.1. Alpha blockers: (24 studies, 2061 participants). We are uncertain about the effects of these drugs on prostatitis symptoms when compared to placebo at short-term follow-up (mean difference (MD) in total NIH-CPSI score -5.01, 95% confidence interval (CI) -7.41 to -2.61; 18 studies, 1524 participants, very low QoE) and at long-term follow-up (MD -5.60, 95% CI -10.89 to -0.32; 4 studies, 235 participants, very low QoE). Alpha blockers may be associated with an increased incidence of adverse events, such as dizziness and postural hypotension (risk ratio (RR) 1.60, 95% CI 1.09 to 2.34; 19 studies, 1588 participants; low QoE). Alpha blockers probably result in little to no difference in sexual dysfunction, quality of life and anxiety and depression (moderate to low QoE).2. 5-alpha reductase inhibitors (5-ARI): (2 studies, 177 participants). Finasteride probably reduces prostatitis symptoms compared to placebo (NIH-CPSI score MD -4.60, 95% CI -5.43 to -3.77; 1 study, 64 participants; moderate QoE) and may not be associated with an increased incidence of adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.3. Antibiotics: (6 studies, 693 participants). Antibiotics (quinolones) may reduce prostatitis symptoms compared to placebo (NIH-CPSI score MD -2.43, 95% CI -4.72 to -0.15; 5 studies, 372 participants; low QoE) and are probably not associated with an increased incidence in adverse events (moderate QoE). Antibiotics probably result in little to no difference in sexual dysfunction and quality of life (moderate QoE). There was no information on anxiety or depression.4. Anti-inflammatories: (7 studies, 585 participants). Anti-inflammatories may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -2.50, 95% CI -3.74 to -1.26; 7 studies, 585 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.5. Phytotherapy: (7 studies, 551 participants). Phytotherapy may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -5.02, 95% CI -6.81 to -3.23; 5 studies, 320 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). Phytotherapy may not improve sexual dysfunction (low QoE). There was no information on quality of life or anxiety and depression.6. Botulinum toxin A (BTA): Intraprostatic BTA injection (1 study, 60 participants) may cause a large reduction in prostatitis symptom (NIH-CPSI scores MD -25.80, 95% CI -30.15 to -21.45), whereas pelvic floor muscle BTA injection (1 study, 29 participants) may not reduce prostatitis symptoms (low QoE). Both comparisons used a placebo injection. These interventions may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.7. Allopurinol: (2 studies, 110 participants). Allopurinol may result in little to no difference in prostatitis symptoms and adverse events when compared to placebo (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.8. Traditional Chinese medicine (TCM): (7 studies, 835 participants); TCM may reduce prostatitis symptoms (NIH-CPSI score, MD -3.13, 95% CI -4.99 to -1.28; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). TCM probably does not improve sexual dysfunction (moderate QoE) and may not improve symptoms of anxiety and depression (low QoE). There was no information on quality of life.The most frequent reasons for downgrading the QoE were study limitations, inconsistency and imprecision. We found few trials with active comparators.
AUTHORS' CONCLUSIONS
We found low- to very low-quality evidence that alpha blockers, antibiotics, 5-ARI, anti-inflammatories, phytotherapy, intraprostatic BTA injection, and traditional Chinese medicine may cause a reduction in prostatitis symptoms without an increased incidence of adverse events in the short term, except for alpha blockers which may be associated with an increase in mild adverse events. We found few trials with active comparators and little evidence of the effects of these drugs on sexual dysfunction, quality of life or anxiety and depression. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient-important outcomes, including potential treatment-related adverse events, and appropriate sample sizes.
PubMed: 31587256
DOI: 10.1002/14651858.CD012552.pub2 -
Nutrition, Metabolism, and... Oct 2019Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia.
METHODS AND RESULTS
PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included.
CONCLUSION
Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia.
REGISTRATION NUMBER
PROSPERO(CRD42018091657).
Topics: Aged; Allopurinol; Asymptomatic Diseases; Biomarkers; Enzyme Inhibitors; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Uric Acid; Xanthine Oxidase
PubMed: 31378626
DOI: 10.1016/j.numecd.2019.06.016 -
Journal of Clinical Pharmacy and... Aug 2019Tumour lysis syndrome is an oncological emergency, characterized by rapid cytolysis leading to an abrupt rise of serum uric acid levels. The aim of the present... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Tumour lysis syndrome is an oncological emergency, characterized by rapid cytolysis leading to an abrupt rise of serum uric acid levels. The aim of the present meta-analysis is to evaluate the efficacy and safety of febuxostat as a preventive measure in patients at risk of tumour lysis syndrome development, by comparing it with allopurinol administration.
METHODS
MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar databases were searched from inception to 15 December 2018. All studies evaluating the effectiveness of febuxostat in preventing tumour lysis syndrome were held eligible.
RESULTS AND DISCUSSION
Six studies were included with a total of 658 patients. Compared to allopurinol, febuxostat achieved a similar response rate (OR: 1.39, 95% CI: [0.55, 3.51]) and tumour lysis syndrome incidence (OR: 1.01, 95% CI: [0.56, 1.81]). Serum uric acid levels did not differ between the investigated groups at the second (MD: -0.21 mg/dL, 95% CI: [-1.30, 0.88]) and seventh (MD: -0.43 mg/dL, 95% CI: [-1.38, 0.51]) day of treatment. Elevation of liver function tests was the most common adverse effect, although its incidence was similar among patients treated with allopurinol and febuxostat.
WHAT IS NEW AND CONCLUSIONS
The present meta-analysis suggests that febuxostat may serve as an effective alternative to allopurinol in the prevention of tumour lysis syndrome. Future large-scale studies should define the optimal febuxostat dosage, explore the most appropriate population for its administration and better define its safety profile.
Topics: Allopurinol; Animals; Febuxostat; Gout Suppressants; Humans; Tumor Lysis Syndrome; Uric Acid
PubMed: 30972811
DOI: 10.1111/jcpt.12839 -
Joint Bone Spine Jul 2019A systematic review and meta-analysis were conducted to investigate the associations of hyperuricemia, gout, and uric acid (UA)-lowering therapy with the risk of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A systematic review and meta-analysis were conducted to investigate the associations of hyperuricemia, gout, and uric acid (UA)-lowering therapy with the risk of fractures.
METHODS
Electronic searches on PubMed, the Cochrane Library, and Embase were conducted from inception to January 2, 2019. Observational studies assessing the effects of hyperuricemia, gout, and UA-lowering therapy on fractures were included in the meta-analysis. Summary risk estimates with 95% confidence intervals (CI) were calculated by a random-effects model.
RESULTS
A total of 14 eligible studies with 909 803 participants and 64 047 incident fractures were included. The results suggested that hyperuricemia and gout are not associated with any type of fracture (relative risk [RR], 0.98, 95% CI 0.85-1.11; P = 0.71) or osteoporotic fractures (RR, 1.02, 95% CI 0.90-1.14; P = 0.79). Further analysis indicated that hyperuricemia is associated with a lower risk of fractures (RR, 0.80, 95% CI 0.66-0.96; P = 0.02) but not with osteoporotic fractures (RR, 0.84, 95% CI 0.68-1.03; P = 0.10). However, gout is associated with an increased risk of fractures (RR, 1.17, 95% CI 1.04-1.31; P = 0.007) as well as osteoporotic fractures (RR, 1.13, 95% CI 1.00-1.26; P = 0.045). Furthermore, no significant association of UA-lowering therapy with the risk of fractures was found compared with the placebo (RR, 0.88, 95% CI 0.76-1.03; P = 0.11). Evidence supporting a non-linear association between serum UA levels and fractures was found (P < 0.001 for non-linearity), which revealed a U-shaped curve.
CONCLUSION
Our meta-analysis revealed that hyperuricemia was associated with lower risk for any type fracture but not associated with osteoporotic fractures; however, gout was associated with an increased risk of any type fracture as well as osteoporotic fractures. Notably, a U-shaped relationship may exist between the serum UA level and fractures. The associations observed in our study may be due to reasons other than causality.
Topics: Allopurinol; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Observational Studies as Topic; Osteoporotic Fractures; Patient Safety; Risk Assessment
PubMed: 30910706
DOI: 10.1016/j.jbspin.2019.03.003 -
International Journal of Rheumatology 2019Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible...
BACKGROUND
Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial.
OBJECTIVE
To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group.
METHODS
We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI).
RESULTS
Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03).
CONCLUSIONS
Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.
PubMed: 30863448
DOI: 10.1155/2019/1076189 -
Journal of Cardiovascular Pharmacology May 2019Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although... (Meta-Analysis)
Meta-Analysis
Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09-0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien-Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.
Topics: Acute Kidney Injury; Allopurinol; Contrast Media; Cytoprotection; Fluid Therapy; Gout Suppressants; Humans; Incidence; Kidney; Network Meta-Analysis; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 30829731
DOI: 10.1097/FJC.0000000000000663 -
Therapeutic Advances in Musculoskeletal... Dec 2018We aimed to systematically review the effectiveness of healthcare behavioral and education interventions for gout patients on clinical outcomes. (Review)
Review
BACKGROUND
We aimed to systematically review the effectiveness of healthcare behavioral and education interventions for gout patients on clinical outcomes.
METHODS
We searched multiple databases to identify trials or observational studies of educational or behavioral interventions in gout. Risk of bias was assessed with the Cochrane tool for randomized control trials (RCTs) and the Newcastle-Ottawa Scale for observational studies. We estimated odds ratios (ORs) for categorical and standardized mean difference (SMD) for continuous measures using a random-effects model.
RESULTS
Overall, eight (five RCTs and three observational) studies met the inclusion criteria and examined pharmacist-led interventions ( = 3), nurse-led interventions ( = 3) and primary care provider interventions ( = 2). Compared with the control intervention (usual care in most cases), a higher proportion of those in the educational/behavioral intervention arm achieved serum urate (SU) levels <6 mg/dl, 47.2% 23.8%, the OR was 4.86 [95% confidence interval (CI), 1.48, 15.97; 4 RCTs] with moderate quality evidence. Compared with the control intervention, a higher proportion of those in the educational/behavioral intervention arm were adherent to allopurinol, achieved at least a 2 mg/dl decrease in SU, achieved an SU < 5 mg/dl, had a reduction in the presence of tophi at 2 years, had improved quality of life as assessed with SF-36 physical component scores, had a higher knowledge about gout and higher patient satisfaction (moderate-low quality evidence).
CONCLUSION
Educational and behavioral interventions can improve gout outcomes in the short-intermediate term. Randomized trials are needed to assess its impact on long-term gout outcomes.
PubMed: 30515250
DOI: 10.1177/1759720X18807117