Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus ...allergen avoidance or placebo (no oral immunotherapy) for peanut allergy.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930.
12 trials (n=1041; median age across trials 8·7 years IQR 5·9–11·2) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio RR 3·12 95% CI 1·76–5·55, I2=0%, risk difference RD 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio IRR 2·72 1·57–4·72, I2=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 1·27–3·83, I2=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (pinteraction=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 1·00–3·66, I2=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 95%CI 1·35–2·38, I2=0%, high-certainty; angioedema: 2·25 1·13–4·47, I2=0%, high-certainty; upper tract respiratory reactions: 1·36 1·02–1·81, I2=0%, moderate-certainty; lower tract respiratory reactions: 1·55 0·96–2·50, I2=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 95% CI 6·82–22·61, I2=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 0·87–1·69, I2=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses.
In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed.
None.
Systematic scoping review, focusing on randomized clinical trials of recent research addressing tree nut allergy.
This review addresses published, unpublished, and re-analyzed studies on tree nut ...allergy definition, epidemiology, etiology, diagnosis, prognosis, and therapy.
The importance of tree nut allergy spans nations, economies, and cultures. While broad themes in epidemiology, etiology, diagnosis, prognosis, and therapy are emerging, the next major advance in tree nut allergy will require large, robust studies to deliver results important to patients and families.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
We compared the effects of mAbs and aspirin desensitization ...(ASA-D) for treatment of CRSwNP.
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference MD −19.91 95% confidence interval (CI) −22.50, −17.32), omalizumab (MD −16.09 95% CI −19.88, −12.30), mepolizumab (MD −12.89 95% CI −16.58, −9.19, ASA-D (MD −10.61 95% CI −14.51, −6.71), and benralizumab (MD −7.68 95% CI −12.09, −3.27). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference RD −16.35% 95% CI −18.13, −13.48), omalizumab (RD −7.40% 95% CI −11.04, −2.43), mepolizumab (RD −12.33% 95% CI −15.56, −7.22), and ASA-D (RD −16.00% 95% CI −19.79, 0.21; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Display omitted
Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co‐morbidities, complexity in care pathways and ...differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home‐based) and its cost‐effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of ...liberal versus conservative oxygen therapy in acutely ill adults.
In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697.
25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen SpO2 across trials, 96% range 94–99%, IQR 96–98) increased mortality in-hospital (relative risk RR 1·21, 95% CI 1·03–1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01–1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00–1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.
In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94–96%. These results support the conservative administration of oxygen therapy.
None.
Assessing the certainty of evidence from network meta-analyses using the GRADE (grading of recommendations, assessment, development, and evaluations) approach requires not only a thorough ...understanding of the methods but also substantial workload for raters. This article describes how implementing practical strategies (including rule setting and automation) can facilitate efficient application of the GRADE approach to rating certainty of evidence in network meta-analyses while maintaining rigor. This article describes a stepwise strategy for proceeding through the process, including assessment of the certainty of direct, indirect, and NMA estimates; developing directions for each step in the process; implementation of rules to improve robustness of information appraisal to reduce workload; and alternatives for automation of some of the required steps. The presented approach includes a detailed description of every step of the process supported by figures, tables, and real life examples. To facilitate implementation of this process, a spreadsheet that incorporates automation of several of the steps described is also provided (https://www.covid19lnma.com/).
Drug allergy: A 2022 practice parameter update Khan, David A.; Banerji, Aleena; Blumenthal, Kimberly G. ...
Journal of allergy and clinical immunology,
December 2022, 2022-12-00, 20221201, Letnik:
150, Številka:
6
Journal Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face ...masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.
We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.
Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio aOR 0·18, 95% CI 0·09 to 0·38; risk difference RD −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk RR 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.
The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.
World Health Organization.
Background
Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the efficacy, safety, and ...pharmacokinetics of direct oral anticoagulants (DOACs) is unknown.
Aims
In this review, we summarize the evidence supporting the use of DOACs after bariatric surgery and apply our findings to resolve several clinical cases.
Materials & Methods
We systematically searched MEDLINE, EMBASE, Cochrane Library, CINAHL and ClinicalTrials.gov from January 1, 2000, to June 15, 2021 for randomized and non‐randomized studies evaluating the use of DOACs for any indication after bariatric surgery. Two reviewers independently screened titles, s, and full‐text articles. Clinical and pharmacokinetic outcomes were pooled by random‐effects meta‐analysis with inverse variance weighting. We used the Newcastle‐Ottawa scale to assess risk of bias in non‐randomized studies and assessed the certainty of evidence with GRADE.
Results
From 2519 records, we included 28 studies (n = 3229 patients): no randomized trials, 7 cohort studies, 6 case series, and 15 case reports. Incidence rates for arterial thromboembolism, venous thromboembolism and major bleeding were: 0.73 (95% confidence interval CI: 0.01–5.10), 2.45 (95% CI: 0.40–7.94), and 3.40 (95% CI: 0.80‐9.36) events per 100 patient‐years, respectively. The pooled proportion of peak direct oral anticoagulant drug levels within the expected range was 58% (95% CI: 39%–74%).
Conclusion
There appears be substantial risk of DOAC malabsorption after bariatric surgery that could affect clinical outcomes, however the certainty of evidence was very low. PROSPERO: CRD42020202636.
PDF
