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JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035 -
International Journal of Medical... Mar 2022Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no... (Review)
Review
BACKGROUND AND OBJECTIVE
Drug allergy alert systems (DAAS), have been considered an effective strategy to reduce preventable adverse drug events (ADEs), improving patient's safety. To date, no review has been conducted analyzing characteristics of DAAS in the hospital setting. Therefore, the aim of this study is to identify, describe and summarize the DAAS used in hospitals. The secondary objectives are to analyse drug allergy alerts (DAA) characteristics, the override rate (OvR) and the clinical consequences of alert overrides.
METHODS
Searches were conducted in Medline and Cochrane Library to identify studies describing DAAS. Systems characteristics, generated alerts, DAA, OvR, and its clinical consequences were extracted and analyzed.
RESULTS
Twenty-eight articles were included in the review. Seventeen different electronic DAAS were identified, of which 53% were commercially available. Systems differed in drug allergy information and rules for generating alerts. DAA were generally interruptive, triggered by non-exact match at drug prescribing and when ignored, an override reason was mandatory. The OvR ranged from 43.7% to 97%. The main override reason given by providers was that 'patient had previously tolerated or had taken the drug without allergic reaction'. Clinical consequences of overriding DAA were only analyzed in four studies, with an ADE incidence between 0% and 6%.
CONCLUSIONS
Different DAAS are used in hospitals with some degree of heterogeneity. Accurate and updated drug allergy information is important to generate only high value alerts. A regular review of DAAS and a standardization of alert rules, alert information and override reasons are necessary to optimize systems. Future studies should evaluate the impact of the DAAS aspects on preventing ADEs.
Topics: Decision Support Systems, Clinical; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Medical Order Entry Systems; Medication Systems
PubMed: 34990941
DOI: 10.1016/j.ijmedinf.2021.104673 -
Annals of Internal Medicine Nov 2020Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.
PURPOSE
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
STUDY SELECTION
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries.
DATA EXTRACTION
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
LIMITATIONS
Only English-language studies were included. The number of head-to-head comparisons was limited.
CONCLUSION
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
PRIMARY FUNDING SOURCE
National Safety Council. (PROSPERO: CRD42018094412).
Topics: Acetaminophen; Acute Pain; Administration, Oral; Administration, Topical; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Comparative Effectiveness Research; Diclofenac; Drug Eruptions; Gastrointestinal Diseases; Humans; Musculoskeletal System; Nervous System Diseases; Network Meta-Analysis; Patient Satisfaction; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 32805127
DOI: 10.7326/M19-3601 -
The Cochrane Database of Systematic... Nov 2022Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice... (Review)
Review
BACKGROUND
Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as insomnia, anxiety or depression. OBJECTIVES: To assess the effects of Ginkgo biloba for tinnitus in adults and children.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2022, Issue 6); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 June 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) recruiting adults and children with acute or chronic subjective tinnitus. We included studies where the intervention involved Ginkgo biloba and this was compared to placebo, no intervention, or education and information. Concurrent use of other medication or other treatment was acceptable if used equally in each group. Where an additional intervention was used equally in both groups, we analysed this as a separate comparison. The review included all courses of Ginkgo biloba, regardless of dose regimens or formulations, and for any duration of treatment.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were tinnitus symptom severity measured as a global score on a multi-item tinnitus questionnaire and serious adverse effects (bleeding, seizures). Our secondary outcomes were tinnitus loudness (change in subjective perception), tinnitus intrusiveness, generalised depression, generalised anxiety, health-related quality of life and other adverse effects (gastrointestinal upset, headache, allergic reaction). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
This review included 12 studies (with a total of 1915 participants). Eleven studies compared the effects of Ginkgo biloba with placebo and one study compared the effects of Ginkgo biloba with hearing aids to hearing aids alone. All included studies were parallel-group RCTs. In general, risk of bias was high or unclear due to selection bias and poor reporting of allocation concealment and blinding of participants, personnel and outcome assessments. Due to heterogeneity in the outcomes measured and measurement methods used, only limited data pooling was possible. Ginkgo biloba versus placebo When we pooled data from two studies for the primary outcome tinnitus symptom severity, we found that Ginkgo biloba may have little to no effect (Tinnitus Handicap Inventory scores) at three to six months compared to placebo, but the evidence is very uncertain (mean difference (MD) -1.35 (scale 0 to 100), 95% confidence interval (CI) -8.26 to 5.55; 2 studies; 85 participants) (very low-certainty). Ginkgo biloba may result in little to no difference in the risk of bleeding or seizures, with no serious adverse effects reported in either group (4 studies; 1154 participants; low-certainty). For the secondary outcomes, one study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on tinnitus loudness measured with audiometric loudness matching at 12 weeks, but the evidence is very uncertain (MD -4.00 (scale -10 to 140 dB), 95% CI -13.33 to 5.33; 1 study; 73 participants) (very low-certainty). One study found that there may be little to no difference between the effects of Ginkgo biloba and placebo on health-related quality of life measured with the Glasgow Health Status Inventory at three months (MD -0.58 (scale 0 to 100), 95% CI -4.67 to 3.51; 1 study; 60 participants) (low-certainty). Ginkgo biloba may not increase the frequency of other adverse effects (gastrointestinal upset, headache, allergic reaction) at three months compared to placebo (risk ratio 0.91, 95% CI 0.52 to 1.60; 4 studies; 1175 participants) (low-certainty). None of the studies reported the other secondary outcomes of tinnitus intrusiveness or changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety. Gingko biloba with concurrent intervention versus concurrent intervention only One study compared Ginkgo biloba with hearing aids to hearing aids only. It assessed the mean difference in the change in Tinnitus Handicap Inventory scores and tinnitus loudness using a 10-point visual analogue scale (VAS) at three months. The study did not report adverse effects, tinnitus intrusiveness, changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life. This was a single, very small study (22 participants) and for all outcomes the certainty of the evidence was very low. We were unable to draw meaningful conclusions from the numerical results.
AUTHORS' CONCLUSIONS
There is uncertainty about the benefits and harms of Ginkgo biloba for the treatment of tinnitus when compared to placebo. We were unable to draw meaningful conclusions regarding the benefits and harms of Ginkgo biloba when used with concurrent intervention (hearing aids). The certainty of the evidence for the reported outcomes, assessed using GRADE, ranged from low to very low. Future research into the effectiveness of Ginkgo biloba in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient-centred outcome measures for research in the field of tinnitus.
Topics: Adult; Child; Humans; Ginkgo biloba; Headache; Hypersensitivity; Seizures; Tinnitus; Randomized Controlled Trials as Topic
PubMed: 36383762
DOI: 10.1002/14651858.CD013514.pub2 -
Journal of Anaesthesiology, Clinical... 2022Perioperative anaphylaxis is a rare, but life-threatening hypersensitivity reaction for patients undergoing surgical procedures. Sugammadex is a relatively new drug used... (Review)
Review
Perioperative anaphylaxis is a rare, but life-threatening hypersensitivity reaction for patients undergoing surgical procedures. Sugammadex is a relatively new drug used to reverse the neuromuscular blockade of specific anesthetics in surgery. Several case reports indicate that there may be a risk of anaphylaxis associated with the use of sugammadex This review examines the literature in order to evaluate the strength of the association between sugammadex use and anaphylaxis. A query of PubMed, EMBASE, and Web of Science was conducted using a combination of terms to identify relevant articles from inception until March 9, 2020. We included any primary study that identified sugammadex as a probable causative agent based on the World Allergy Organization diagnostic criteria for anaphylaxis. A total of 24 articles were reviewed. Across the three randomized controlled trials, there were only four cases of anaphylaxis identified. Incidence of anaphylaxis was reported in only one trial at 0.33%. Two retrospective observational studies conducted in Japan identified cases of anaphylaxis, with incidences of 0.02 and 0.04%. Among 19 case reports and series, 25 patient cases of anaphylaxis were confirmed via allergy testing to be caused by sugammadex or sugammadex-rocuronium complex. Commonly reported symptoms included hypotension, erythema, and decreased oxygen saturation. Based on the findings of this review, there appears to be a rare, but serious, association of sugammadex-induced perioperative anaphylaxis with an incidence between 0.02 and 0.04% in observational studies. It is unclear whether sugammadex on its own or in complex with rocuronium triggers this reaction, but it is clearly involved in inducing anaphylaxis. Further population studies are needed to get a more accurate global incidence rate, and more detailed allergy testing is required to better describe which step of the sugammadex reversal pathway initiates the anaphylactic attack.
PubMed: 36505200
DOI: 10.4103/joacp.JOACP_573_20 -
Frontiers in Allergy 2022Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase...
Gadolinium-based contrast agents (GBCAs) are frequently used in magnetic resonance imaging (MRI) examinations to increase sensitivity in diagnoses. Recently, an increase in the description of hypersensitivity reactions to GBCAs has been detected. We performed research in PubMed, PubMed, SCOPUS, and EMBASE until September 2021, searching for studies regarding immediate and delayed hypersensitivity reactions to gadolinium-based contrast agents in which an allergy study was performed. The initial research identified 149 articles written in English. After excluding articles duplicated and articles that had irrelevant designs, 26 articles were included. Finally, 17 studies concerning immediate reactions, six studies concerning non-immediate reactions, and three concerning both that performed allergy evaluations were selected. In the review, we analyzed the characteristics of immediate and delayed reactions and the results of the allergy study and cross-reactivity. Skin tests seem to have acceptable accuracy, but drug provocation tests are still needed when skin tests are negative o to find alternative agents. Although cross-reactivity patterns are not well established, cross-reactivity seems to exist among macrocyclic agents. Notwithstanding, the number of patients analyzed is low and further studies are required. A management algorithm is suggested.
PubMed: 35386665
DOI: 10.3389/falgy.2022.813927 -
The Cochrane Database of Systematic... Apr 2020Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights the need for interventions to increase physical activity participation. The widely-accepted benefits of physical activity, coupled with the increasing availability of wearable monitoring devices to objectively measure participation, has led to a dramatic rise in the number and variety of studies that aimed to improve the physical activity of people with COPD. However, little was known about the relative efficacy of interventions tested so far.
OBJECTIVES
In people with COPD, which interventions are effective at improving objectively-assessed physical activity?
SEARCH METHODS
We identified trials from the Cochrane Airways Trials Register Register, which contains records identified from bibliographic databases including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and PsycINFO. We also searched PEDro, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform portal and the Australian New Zealand Clinical Trials Registry (from inception to June 2019). We checked reference lists of all primary studies and review articles for additional references, as well as respiratory journals and respiratory meeting abstracts, to identify relevant studies.
SELECTION CRITERIA
We included randomised controlled trials of interventions that used objective measures for the assessment of physical activity in people with COPD. Trials compared an intervention with no intervention or a sham/placebo intervention, an intervention in addition to another standard intervention common to both groups, or two different interventions.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. Subgroup analyses were possible for supervised compared to unsupervised pulmonary rehabilitation programmes in clinically-stable COPD for a range of physical activity outcomes. Secondary outcomes were health-related quality of life, exercise capacity, adverse events and adherence. Insufficient data were available to perform prespecified subgroup analyses by duration of intervention or disease severity. We undertook sensitivity analyses by removing studies that were at high or unclear risk of bias for the domains of blinding and incomplete outcome data.
MAIN RESULTS
We included 76 studies with 8018 participants. Most studies were funded by government bodies, although some were sponsored by equipment or drug manufacturers. Only 38 studies had physical activity as a primary outcome. A diverse range of interventions have been assessed, primarily in single studies, but improvements have not been systematically demonstrated following any particular interventions. Where improvements were demonstrated, results were confined to single studies, or data for maintained improvement were not provided. Step count was the most frequently reported outcome, but it was commonly assessed using devices with documented inaccuracy for this variable. Compared to no intervention, the mean difference (MD) in time in moderate- to vigorous-intensity physical activity (MVPA) following pulmonary rehabilitation was four minutes per day (95% confidence interval (CI) -2 to 9; 3 studies, 190 participants; low-certainty evidence). An improvement was demonstrated following high-intensity interval exercise training (6 minutes per day, 95% CI 4 to 8; 2 studies, 275 participants; moderate-certainty evidence). One study demonstrated an improvement following six months of physical activity counselling (MD 11 minutes per day, 95% CI 7 to 15; 1 study, 280 participants; moderate-certainty evidence), but we found mixed results for the addition of physical activity counselling to pulmonary rehabilitation. There was an improvement following three to four weeks of pharmacological treatment with long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) compared to placebo (MD 10 minutes per day, 95% CI 4 to 15; 2 studies, 423 participants; high-certainty evidence). These interventions also demonstrated improvements in other measures of physical activity. Other interventions included self-management strategies, nutritional supplementation, supplemental oxygen, endobronchial valve surgery, non-invasive ventilation, neuromuscular electrical stimulation and inspiratory muscle training.
AUTHORS' CONCLUSIONS
A diverse range of interventions have been assessed, primarily in single studies. Improvements in physical activity have not been systematically demonstrated following any particular intervention. There was limited evidence for improvement in physical activity with strategies including exercise training, physical activity counselling and pharmacological management. The optimal timing, components, duration and models for interventions are still unclear. Assessment of quality was limited by a lack of methodological detail. There was scant evidence for a continued effect over time following completion of interventions, a likely requirement for meaningful health benefits for people with COPD.
Topics: Exercise; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Telerehabilitation
PubMed: 32297320
DOI: 10.1002/14651858.CD012626.pub2 -
The Journal of Infection Sep 2023Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
METHODS
We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961.
RESULTS
Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5).
CONCLUSION
Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
Topics: Humans; Adult; Pregnancy; Female; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Antitubercular Agents
PubMed: 37356629
DOI: 10.1016/j.jinf.2023.06.014 -
Pain Jul 2021We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.
We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
Topics: Analgesics; Animals; Cannabinoids; Cannabis; Endocannabinoids; Male; Models, Animal; Neuralgia
PubMed: 33729209
DOI: 10.1097/j.pain.0000000000002269 -
The Journal of Allergy and Clinical... Jan 2021Having a penicillin allergy label associates with a higher risk for antibiotic resistance and increased health care use. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Having a penicillin allergy label associates with a higher risk for antibiotic resistance and increased health care use.
OBJECTIVE
We sought to assess the accuracy of skin tests and specific IgE quantification in the diagnostic evaluation of patients reporting a penicillin/β-lactam allergy.
METHODS
We performed a systematic review and diagnostic accuracy meta-analysis, searching on MEDLINE, Scopus, and Web of Science. We included studies conducted in patients reporting a penicillin allergy and in whom skin tests and/or specific IgE quantification were performed and compared with drug challenge results. We quantitatively assessed the accuracy of diagnostic tests with bivariate random-effects meta-analyses. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. Studies' quality was evaluated using QUADAS-2 criteria.
RESULTS
We included 105 primary studies, assessing 31,761 participants. Twenty-seven studies were assessed by bivariate meta-analysis. Skin tests had a summary sensitivity of 30.7% (95% CI, 18.9%-45.9%) and a specificity of 96.8% (95% CI, 94.2%-98.3%), with a partial area under the summary receiver-operating characteristic curve of 0.686 (I = 38.2%). Similar results were observed for subanalyses restricted to patients reporting nonimmediate maculopapular exanthema or urticaria/angioedema. Specific IgE had a summary sensitivity of 19.3% (95% CI, 12.0%-29.4%) and a specificity of 97.4% (95% CI, 95.2%-98.6%), with a partial area under the summary receiver-operating characteristic curve of 0.420 (I = 8.5%). Projected predictive values mainly reflect the low frequency of true penicillin allergy.
CONCLUSIONS
Skin tests and specific IgE quantification appear to have low sensitivity and high specificity. Because current evidence is insufficient for assessing the role of these tests in stratifying patients for delabeling, we identified key requirements needed for future studies.
Topics: Drug Hypersensitivity; Humans; Immunoglobulin E; Penicillins; Skin Tests
PubMed: 32446963
DOI: 10.1016/j.jaci.2020.04.058