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.
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.
Older people living in nursing care facilities or older adults living at home are at high risk of falling and a hip fracture may occur after a fall. Hip protectors have been advocated as a means to ...reduce the risk of hip fracture. Hip protectors are plastic shields (hard) or foam pads (soft), usually fitted in pockets in specially designed underwear.This is an update of a Cochrane review first published in 1999, and updated several times, most recently in 2010.
To determine if the provision of external hip protectors (sometimes referred to as hip pads or hip protector pads) reduces the risk of fracturing the hip in older people.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE (1950 to week 3 November 2012), MEDLINE In-Process (18 December 2012), EMBASE (1988 to 2012 Week 50), CINAHL (1982 to December 2012), BioMed Central (January 2010), trial registers and reference lists of relevant articles.
All randomised or quasi-randomised controlled trials comparing an intervention group provided with hip protectors with a control group not provided with hip protectors.
Two review authors independently assessed risk of bias and extracted data. We sought additional information from trialists. Data were pooled using fixed-effect or random-effects models as appropriate.
This review includes 19 studies, nine of which were cluster randomised. These included approximately 17,000 people (mean age range 78 to 86 years). Most studies were overall at low risk of bias for fracture outcomes. Trials tested hard or soft hip protectors enclosed in special underwear in 18 studies.Pooling of data from 14 studies (11,808 participants) conducted in nursing or residential care settings found moderate quality evidence for a small reduction in hip fracture risk (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.67 to 1.00); the absolute effect is 11 fewer people (95% CI, from 20 fewer to 0) per 1000 having a hip fracture when provided with hip protectors.There is moderate quality evidence when pooling data from five trials in the community (5614 participants) that shows little or no effect in hip fracture risk (RR 1.15, 95% CI 0.84 to 1.58); the absolute effect is two more people (95% CI 2 fewer to 6 more) per 1000 people having a hip fracture when provided with hip protectors.There is probably little to no effect on falls (rate ratio 1.02, 95% CI 0.9 to 1.16) or fractures other than of the hip or pelvis (rate ratio 0.87, 95% CI 0.71 to 1.07). However, the risk ratio for pelvic fractures is RR 1.27 (95% CI 0.78 to 2.08); this is an absolute effect of one more person (95% CI 1 fewer to 5 more) per 1000 having a pelvic fracture when provided with hip protectors.The incidence of adverse events while wearing hip protectors, including skin irritation, ranged from 0% to 5%. Adherence, particularly in the long term, was poor.
Hip protectors probably reduce the risk of hip fractures if made available to older people in nursing care or residential care settings, without increasing the frequency of falls. However, hip protectors may slightly increase the small risk of pelvic fractures. Poor acceptance and adherence by older people offered hip protectors is a barrier to their use. Better understanding is needed of the personal and design factors that may influence acceptance and adherence.
Abstract Introduction To compare neonatal, obstetrical, and maternal outcomes associated with outpatient versus inpatient management of pregnancies with preterm prelabor rupture of membranes (PPROM). ...Material and Methods A search of MEDLINE, EMBASE, the Cochrane Database and Central Register from January 1, 1990 to July 31, 2023 identified randomized controlled trials (RCTs) and cohort studies comparing outpatient with inpatient management for pregnant persons diagnosed with PPROM before 37 weeks' gestation. No language restriction was applied. We applied a random effects model for meta‐analysis. Trustworthiness was assessed using recently published guidance and Risk of bias using the RoB 2.0 tool for RCTs and ROBINS‐I tool for cohort studies. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the certainty of evidence (COE). Outcomes of interest included perinatal mortality, neonatal morbidities, latency and gestational age at delivery, and maternal morbidities. RCTs and cohort studies were analyzed separately. This study was registered in the International Prospective Register of Systematic Reviewsr: CRD42022295275. Results From 2825 records, two RCTs and 10 cohort studies involving 1876 patients were included in the review and meta‐analysis. Outpatient management protocols varied but generally included brief initial hospitalization, strict eligibility criteria, and surveillance with laboratory and ultrasound investigations. Outpatient management showed lower rates of neonatal respiratory distress syndrome (cohort: RR 0.63 0.52–0.77, very low COE), longer latency to delivery (RCT: MD 7.43 days 1.14–13.72 days, moderate COE, cohort: MD 8.78 days 2.29–15.26 days, low COE), higher gestational age at birth (cohort: MD 7.70 days 2.02–13.38 days, low COE), lower rates of Apgar scores <7 at 5 min of life (cohort: RR 0.66 0.50–0.89, very low COE), and lower rates of histological chorioamnionitis (cohort: RR 0.74 0.62–0.89, low COE) without increased risks of adverse neonatal, obstetrical, or maternal outcomes. Conclusions Meta‐analysis of data from RCTs and cohort studies with very low‐to‐moderate certainty of evidence indicates that further high‐quality research is needed to evaluate the safety and potential benefits of outpatient management for selected PPROM cases, given the moderate‐to‐high risk of bias in the included studies.
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Living systematic review and network meta-analysis.
WHO covid-19 database, a comprehensive multilingual source of global ...covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis.
Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low.
Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain.
This review was not registered. The protocol is publicly available in the supplementary material.
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
Method’s corner: Allergist’s guide to network meta‐analysis Chu, Derek K.; Brignardello‐Petersen, Romina; Guyatt, Gordon H. ...
Pediatric allergy and immunology,
January 2022, 2022-01-00, 20220101, Letnik:
33, Številka:
1
Journal Article
Recenzirano
Network meta‐analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must ...understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta‐analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.
Objective
To compare the relative efficacy and safety of pharmacologic antiinflammatory interventions for gout flares.
Methods
We searched Ovid Medline, Embase, and Cochrane library for randomized ...controlled trials (RCTs) that compared pharmacologic antiinflammatory treatment of gout flares. We conducted a network meta‐analysis (NMA) using a frequentist framework and assessed the certainty of evidence and made conclusions using the Grading of Recommendations Assessment, Development, and Evaluation for NMA.
Results
In the 30 eligible RCTs, canakinumab provided the highest pain reduction at day 2 and at longest follow‐up (mean difference relative to acetic acid derivative nonsteroidal antiinflammatory drugs NSAIDs –41.12 95% confidence interval (95% CI) –53.36, –29.11 on a 0–100 scale at day 2, and mean difference –12.84 95% CI –20.76, –4.91 at longest follow‐up; both moderate certainty; minimum important difference –19). Intravenous or intramuscular corticosteroids were inferior to canakinumab but may be better than the other commonly used interventions (low to very low certainty). For joint tenderness, canakinumab may be the most effective intervention at day 2. Acetic acid derivative NSAIDs improved joint swelling better than ibuprofen NSAIDs at day 2 (mean difference –0.29 95% CI –0.56, –0.02 on a 0–4 scale; moderate certainty) and improved patient global assessment (PtGA) greater than ibuprofen NSAIDs at the longest follow‐up (mean difference –0.44 95% CI –0.86, –0.02; moderate).
Conclusion
Canakinumab may be superior to other alternatives and intravenous or intramuscular corticosteroids may be the second best in pain reduction. Acetic acid derivative NSAIDs may be superior to ibuprofen NSAIDs in improving joint swelling and PtGA.
This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this ...guideline.
What is the role of drugs in the treatment of patients with covid-19?
The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.
The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.
This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.
Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.
Aim
To identify the diagnostic accuracy of gingival crevicular fluid (GCF) candidate biomarkers to discriminate periodontitis from the inflamed and healthy sites, and to compare the performance of ...two independent matrix metalloproteinase (MMP)‐8 immunoassays.
Materials and Methods
Cross sectional study. GCF (N = 58 sites) was collected from healthy, gingivitis and chronic periodontitis volunteers and analysed for levels of azurocidin, chemokine ligand 5, MPO, TIMP‐1 MMP‐13 and MMP‐14 by ELISA or activity assays. MMP‐8 was assayed by immunofluorometric assay (IFMA) and ELISA. Statistical analysis was performed using linear mixed‐effects models and Bayesian statistics in R and Stata V11.
Results
MMP‐8, MPO, azurocidin and total MMP‐13 and MMP‐14 were higher in periodontitis compared to gingivitis and healthy sites (p < 0.05). A very high correlation between MPO and MMP‐8 was evident in the periodontitis group (r = 0.95, p < 0.0001). MPO, azurocidin and total levels of MMP‐8, MMP‐13 and MMP‐14 showed high diagnostic accuracy (≥0.90), but only MMP‐8 and MPO were significantly higher in the periodontitis versus gingivitis sites. MMP‐8 determined by IFMA correlated more strongly with periodontal status and showed higher diagnostic accuracy than ELISA.
Conclusions
MPO and collagenolytic MMPs are highly discriminatory biomarkers for site‐specific diagnosis of periodontitis. The comparison of two quantitative MMP‐8 methods demonstrated IFMA to be more accurate than ELISA.
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