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Expert Opinion on Pharmacotherapy May 2018Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite... (Review)
Review
INTRODUCTION
Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.
AREAS COVERED
The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.
EXPERT OPINION
Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.
Topics: Chronic Disease; Cough; Humans; Treatment Outcome
PubMed: 29658795
DOI: 10.1080/14656566.2018.1462795 -
Clinical and Experimental Allergy :... May 2023Mixed and non-IgE-mediated food allergy is a subset of immune-mediated adverse food reactions that can impose a major burden on the quality of life of affected patients... (Review)
Review
BACKGROUND
Mixed and non-IgE-mediated food allergy is a subset of immune-mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied.
OBJECTIVE
As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non-IgE-mediated food allergy.
DESIGN
In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein-induced enterocolitis syndrome, food protein-induced allergic proctocolitis, food protein-induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022.
RESULTS
Twenty-six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient-reported dysphagia, usually using a non-validated questionnaire. Twenty-two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non-validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient-reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient-reported outcomes.
CONCLUSIONS
Outcomes measured in clinical trials of EoE and non-IgE-mediated food allergy are heterogeneous and largely non-validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non-IgE-mediated food allergies, core outcome development is needed to support the development of effective treatments.
SYSTEMATIC REVIEW REGISTRATION
OSF public registry DOI:10.17605/OSF.IO/AZX8S.
Topics: Adult; Child; Humans; Randomized Controlled Trials as Topic; Food Hypersensitivity; Eosinophilic Esophagitis; Food
PubMed: 36880564
DOI: 10.1111/cea.14304 -
Journal of Clinical Medicine May 2022The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year...
The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year post hoc analysis on the MEREAFaPS Study database was performed (2012−2019). Subjects who experienced drug-related hypersensitivity leading to an ED visit were selected. Logistic regression analyses were used to estimate the reporting odds ratios (RORs) of drug-related allergies and anaphylaxis adjusting for sex, age classes, and ethnicity. In addition, a systematic review of observational studies evaluating drug-related hypersensitivity reactions leading to ED visits in outpatients was performed. Out of 94,073 ED visits, 14.4% cases were drug-related allergies and 0.6% were anaphylaxis. Females accounted for 56%. Multivariate logistic regression showed a higher risk of drug-related allergy among males and all age classes < 65 years, while a higher risk of anaphylaxis was observed for females (ROR 1.20 [1.01−1.42]) and adults (ROR 2.63 [2.21−3.14]). The systematic review included 37 studies. ED visits related to allergy and anaphylaxis ranged from 0.004% to 88%, and drug-related allergies and anaphylaxis ranged from 0.007% to 88%. Both in our analysis and in primary studies, antibacterials, analgesics, and radiocontrast agents were identified as the most common triggers of hypersensitivity.
PubMed: 35628936
DOI: 10.3390/jcm11102811 -
Annals of the Rheumatic Diseases May 2022Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory...
The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.
OBJECTIVE
Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases.
METHODS
Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed.
RESULTS
The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS.
CONCLUSION
These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.
Topics: Autoimmune Diseases of the Nervous System; Erythema Nodosum; Fingers; Humans; Nervous System Malformations; Quality of Life; Rheumatology; Skin Diseases
PubMed: 35086813
DOI: 10.1136/annrheumdis-2021-221814 -
Allergy Sep 2017A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization.
METHODS
We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included.
RESULTS
Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies.
CONCLUSIONS
Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Health Care Costs; Humans; Inpatients; Penicillins; Predictive Value of Tests; Treatment Outcome
PubMed: 28370003
DOI: 10.1111/all.13168 -
The American Journal of Medicine Apr 2020True allergy to penicillin is rare, despite the high frequency with which it is reported. While most patients reporting penicillin allergy are not prone to anaphylaxis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
True allergy to penicillin is rare, despite the high frequency with which it is reported. While most patients reporting penicillin allergy are not prone to anaphylaxis, it is not currently known what percentage of these patients will tolerate dose challenges of penicillin-based antibiotics. This review aims to determine the rate of tolerance in patients reporting penicillin allergy when challenged with penicillin-based antibiotics.
METHODS
We searched MedLine, Embase, and Cochrane Library for publications with English language translations between the years 2000 and 2017. We included randomized controlled trials, quasi-experimental, and observational studies of participants reporting penicillin allergy who received at least one systemic dose of a penicillin in the form of a drug challenge. At least 2 independent reviewers extracted data from included studies and assessed the quality of each included study. To generate primary outcome data, we calculated a summary estimate rate of penicillin tolerance from a pooled proportion of participants receiving penicillin with no adverse effects.
RESULTS
Initial literature search yielded 2945 studies, of which 23 studies were ultimately included in our review; 5056 study participants with reported history of penicillin allergy were challenged with a penicillin. After weighting for study sample size, a pooled average of 94.4% (95% confidence interval, 93.7%-95%) of participants tolerated the dose challenge without any adverse reaction.
CONCLUSION
Misrepresented penicillin allergy drives unnecessary use of alternative antibiotics, which may be less effective, more toxic, and more expensive than using penicillin. In addressing the problem of penicillin allergy over-diagnosis, evaluation should go beyond risk for type 1 hypersensitivity. Our data suggest that 94.4% of 5056 participants with reported penicillin allergy determined to be clinically appropriate for allergy evaluation tolerated repeat administration of penicillin-based antibiotics without any adverse reactions. This review generates meaningful information useful to clinical predictive analytics, in evaluating and managing patients with a reported history of penicillin allergy.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Penicillins
PubMed: 31647915
DOI: 10.1016/j.amjmed.2019.09.017 -
Giornale Italiano Di Dermatologia E... Dec 2016Part of the acquired hyperpigmentations of the skin are interpreted as adverse effect of drugs. However, systematic studies are rare in the literature, as case reports... (Review)
Review
INTRODUCTION
Part of the acquired hyperpigmentations of the skin are interpreted as adverse effect of drugs. However, systematic studies are rare in the literature, as case reports have predominantly been published. The present systematic review attempts to provide a contribution to the body of evidence for a causal relation.
EVIDENCE ACQUISITION
The reports on an association of hyperpigmentation and drugs from 1970 until April 2016 found in Medline and EMBASE were rated according to the SIGN grading system for clinical studies.
EVIDENCE SYNTHESIS
A total of 352 evaluated publications were found, which mainly consist of reports of single cases, only a small number of larger case series were available. Case-control-studies and randomized controlled studies have rarely been found. The level of evidence for a causal relation to hyperpigmentation is low for the major part of drugs as quoted in order to the Anatomical Therapeutic Chemical Classification System with Defined Daily Doses. A causal relation is likely only for prostaglandins, minocyclin, phenothiazine, nicotine, and anti-malaria drugs.
CONCLUSIONS
There is paucity of evidence for an induction of hyperpigmentation by drugs. A causal relationship is likely only in a small number of drugs.
Topics: Drug Eruptions; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperpigmentation; Randomized Controlled Trials as Topic
PubMed: 27248149
DOI: No ID Found -
Current Opinion in Allergy and Clinical... Aug 2023Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or...
PURPOSE OF REVIEW
Serum tryptase, a mast cell marker, provides clues for the mechanism, severity, and management of drug hypersensitivity induced by immunoglobulin E dependent or independent mast cell activation.
RECENT FINDINGS
The interpretation of serum tryptase levels has been challenged during the last 2 years by major advances in tryptase genetics and their rapid incorporation into clinical practice. On the contrary, new pathophysiological insight into nonmast cell-dependent immediate hypersensitivity has been gained.
SUMMARY
This review provides up-to-date information on the pathophysiology and recommended use and interpretation of tryptase in the context of drug hypersensitivity reactions as a function of their endotype.
Topics: Humans; Tryptases; Anaphylaxis; Drug Hypersensitivity; Mast Cells; Hypersensitivity, Immediate
PubMed: 37357783
DOI: 10.1097/ACI.0000000000000916 -
Journal of Immunology Research 2022Frequent mislabelled causal relationship between drug hypersensitivity reactions and culprit drugs reinforces the need for an accurate diagnosis. The systematic reviews... (Meta-Analysis)
Meta-Analysis Review
Frequent mislabelled causal relationship between drug hypersensitivity reactions and culprit drugs reinforces the need for an accurate diagnosis. The systematic reviews and meta-analyses of assays published so far focused on immediate reactions and the most severe delayed reactions, while the most frequent drug-induced delayed reactions-nonsevere exanthemas-have been underestimated. We aim to fill this gap. A systematic review of studies on assays used in the diagnosis of nonsevere drug-induced delayed reactions was conducted following the methodology of Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies Statement. The EMBASE and PubMed databases were searched. We have included 33 studies from which we extracted the data, then performed meta-analysis where possible, or synthesised the evidence narratively. The quality of the analysed studies was assessed with the QUADAS-2 tool. The tests identified the most frequently were lymphocyte transformation test (LTT), ELISpot, and ELISA. In the meta-analysis carried out for LTT in reactions induce by beta-lactams, the pool estimate of sensitivity and specificity amounted to 49.1% (95% CI: 14.0%, 85.0%) and 94.6% (95% CI: 81.7%, 98.6%), respectively. The studies showed heterogeneity in study design and laboratory settings, which resulted in a wide range of specificity and sensitivity of testing.
Topics: Humans; Drug Hypersensitivity; Sensitivity and Specificity; Drug Eruptions; Exanthema; Enzyme-Linked Immunosorbent Assay
PubMed: 36590449
DOI: 10.1155/2022/2386654 -
Journal of Medical Internet Research Sep 2018Worldwide, the burden of allergies-in particular, drug allergies-is growing. In the process of prescribing, dispensing, or administering a drug, a medication error may...
BACKGROUND
Worldwide, the burden of allergies-in particular, drug allergies-is growing. In the process of prescribing, dispensing, or administering a drug, a medication error may occur and can have adverse consequences; for example, a drug may be given to a patient with a documented allergy to that particular drug. Computerized physician order entry (CPOE) systems with built-in clinical decision support systems (CDSS) have the potential to prevent such medication errors and adverse events.
OBJECTIVE
The aim of this review is to provide a comprehensive overview regarding all aspects of CDSS for drug allergy, including documenting, coding, rule bases, alerts and alert fatigue, and outcome evaluation.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed as much as possible and searches were conducted in 5 databases using CPOE, CDSS, alerts, and allergic or allergy as keywords. Bias could not be evaluated according to PRISMA guidelines due to the heterogeneity of study types included in the review.
RESULTS
Of the 3160 articles considered, 60 met the inclusion criteria. A further 9 articles were added based on expert opinion, resulting in a total of 69 articles. An interrater agreement of 90.9% with a reliability Κ=.787 (95% CI 0.686-0.888) was reached. Large heterogeneity across study objectives, study designs, study populations, and reported results was found. Several key findings were identified. Evidence of the usefulness of clinical decision support for drug allergies has been documented. Nevertheless, there are some important problems associated with their use. Accurate and structured documenting of information on drug allergies in electronic health records (EHRs) is difficult, as it is often not clear to healthcare providers how and where to document drug allergies. Besides the underreporting of drug allergies, outdated or inaccurate drug allergy information in EHRs poses an important problem. Research on the use of coding terminologies for documenting drug allergies is sparse. There is no generally accepted standard terminology for structured documentation of allergy information. The final key finding is the consistently reported low specificity of drug allergy alerts. Current systems have high alert override rates of up to 90%, leading to alert fatigue. Important challenges remain for increasing the specificity of drug allergy alerts. We found only one study specifically reporting outcomes related to CDSS for drug allergies. It showed that adverse drug events resulting from overridden drug allergy alerts do not occur frequently.
CONCLUSIONS
Accurate and comprehensive recording of drug allergies is required for good use of CDSS for drug allergy screening. We found considerable variation in the way drug allergy are recorded in EHRs. It remains difficult to reduce drug allergy alert overload while maintaining patient safety as the highest priority. Future research should focus on improving alert specificity, thereby reducing override rates and alert fatigue. Also, the effect on patient outcomes and cost-effectiveness should be evaluated.
Topics: Decision Support Systems, Clinical; Drug Hypersensitivity; Humans; Reproducibility of Results
PubMed: 30194058
DOI: 10.2196/jmir.8206