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Contact Dermatitis Apr 2024Fixed drug eruption (FDE) is a cutaneous drug reaction characterised by recurrent skin lesions occurring at the same site after each exposure to a causative agent. There... (Review)
Review
Fixed drug eruption (FDE) is a cutaneous drug reaction characterised by recurrent skin lesions occurring at the same site after each exposure to a causative agent. There is currently limited evidence in the paediatric population. The objective of this systematic review is to investigate the clinical features, causative agents and management of paediatric FDE. A systematic search of the English and French literature on paediatric FDE was conducted using the Medline and Embase databases. After full-text article review, 92 articles were included, representing a total of 233 patients. Antibiotics were the most frequent triggering agents, mainly sulfonamides (65.0% of antibiotics). Systemic symptoms were rare, and most patients only received supportive therapy. One hundred and six patients (106) performed a test to confirm the causative agent. Of these, 72.6% had oral provocation tests (OPTs) and 28.3% had patch tests. The patient's age, presence of bullous lesions and mucosal lesions were similar between tested and untested patients. It did not seem to influence the decision to perform OPTs. Paediatric FDE is a non-severe skin drug reaction. Antibiotics were the most reported triggering agents. Drug testing, including oral provocation test, was safely performed in the paediatric population.
Topics: Humans; Child; Dermatitis, Allergic Contact; Drug Eruptions; Patch Tests; Anti-Bacterial Agents; Sulfanilamide
PubMed: 38234071
DOI: 10.1111/cod.14500 -
The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
Journal of Autoimmunity Feb 2024The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by... (Review)
Review
The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.
Topics: United States; Adult; Child; Humans; Male; Female; Penicillin G Procaine; Anaphylaxis; Penicillins; Hallucinations; Syndrome; Lung Diseases
PubMed: 38194789
DOI: 10.1016/j.jaut.2023.103164 -
The Journal of Allergy and Clinical... May 2024Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence...
Cost-Effectiveness and Impact on Health Care Utilization of Interventions to Improve Medication Adherence and Outcomes in Asthma and Chronic Obstructive Pulmonary Disease: A Systematic Literature Review.
BACKGROUND
Poor adherence to asthma and chronic obstructive pulmonary disease maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in regular widespread use. Implementation costs are a potential barrier to uptake of such programs.
OBJECTIVE
We undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on health care budget directly or via health care resource use (HCRU).
METHODS
We identified relevant publications using Medline and PreMEDLINE (PubMed), Embase (Embase.com, Elsevier), and EconLit for publications between January 2000 and July 2021. We also searched clinical trial databases and selected conference proceedings.
RESULTS
Of 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included an analysis of biologic medication use. When they were studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU (health care visits, hospital admissions, and/or the use of medications, including add-on/reliever treatment and antibiotics) were frequently reported. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases in which favorable outcomes were observed.
CONCLUSIONS
Adherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.
Topics: Humans; Cost-Benefit Analysis; Asthma; Pulmonary Disease, Chronic Obstructive; Medication Adherence; Patient Acceptance of Health Care
PubMed: 38182099
DOI: 10.1016/j.jaip.2023.12.049 -
The Australasian Journal of Dermatology Mar 2024Toxic epidermal necrolysis (TEN) involves extensive mucocutaneous loss, and care is supportive. The approach to wound care includes surgical debridement or using... (Meta-Analysis)
Meta-Analysis Review
Toxic epidermal necrolysis (TEN) involves extensive mucocutaneous loss, and care is supportive. The approach to wound care includes surgical debridement or using dressings while leaving the epidermis intact. Robust evidence for either approach is lacking. We compared surgical debridement to the use of dressings while leaving the epidermis in situ (referred to hereon as dressings) in adult patients with TEN. The primary outcome assessed was mortality. The secondary outcome was time to re-epithelialisation. The impact of medications was evaluated. An individual patient data (IPD) systematic review and meta-analysis was undertaken. A random effects meta-analysis and survival analysis for IPD data examined mortality, re-epithelisation time and the effect of systemic medications. The quality of evidence was rated per the Grading of Recommendations Assessment, Development and Evaluation (GRADE). PROSPERO: CRD42021266611 Fifty-four studies involving 227 patients were included in the systematic review and meta-analysis, with a GRADE from very low to moderate. There was no difference in survival in patients who had surgical debridement or dressings (univariate: p = 0.91, multivariate: p = 0.31). Patients who received dressings re-epithelialised faster than patients who underwent debridement (multivariate HR: 1.96 [1.09-3.51], p = 0.023). Intravenous immunoglobulin (univariate HR: 0.21 [0.09-0.45], p < 0.001; multivariate HR: 0.22 [0.09-0.53], p < 0.001) and cyclosporin significantly reduced mortality (univariate HR: 0.09 [0.01-0.96], p = 0.046; multivariate HR: 0.06 [0.01-0.73], p = 0.028) irrespective of the wound care. This study supports the expert consensus of the dermatology hospitalists, that wound care in patients with TEN should be supportive with the epidermis left intact and supported with dressings, which leads to faster re-epithelialisation.
Topics: Adult; Humans; Stevens-Johnson Syndrome; Bandages; Cyclosporine; Immunoglobulins, Intravenous
PubMed: 38063272
DOI: 10.1111/ajd.14193 -
The Cochrane Database of Systematic... Dec 2023Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic... (Review)
Review
BACKGROUND
Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear.
OBJECTIVES
To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD.
SEARCH METHODS
We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to 30 November 2022. We also searched ClinicalTrials.gov and the WHO ICTRP up to 30 November 2022.
SELECTION CRITERIA
We included parallel-group randomised controlled trials of three weeks' duration or longer that compared the treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. The primary outcomes were acute exacerbations of COPD, respiratory health-related quality of life, pneumonia and other serious adverse events. The secondary outcomes were symptom scores, lung function, physical capacity, and mortality. We used GRADE to assess certainty of evidence for studies that contributed data to our prespecified outcomes.
MAIN RESULTS
Four studies with a total of 15,412 participants met the inclusion criteria. The mean age of study participants ranged from 64.4 to 65.3 years; the proportion of female participants ranged from 28% to 40%. Most participants had symptomatic COPD (COPD Assessment Test Score ≥ 10) with severe to very severe airflow limitation (forced expiratory volume in one second (FEV1) < 50% predicted) and one or more moderate-to-severe COPD exacerbations in the last 12 months. Trial medications differed amongst studies. The duration of follow-up was 52 weeks in three studies and 24 weeks in one study. We assessed the risk of selection, performance, and detection bias to be low in the included studies; one study was at high risk of attrition bias, and one study was at high risk of reporting bias. Triple therapy may reduce rates of moderate-to-severe COPD exacerbations compared to combination LABA/LAMA inhalers (rate ratio (RR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; n = 15,397; low-certainty evidence). Subgroup analysis stratifying by blood eosinophil counts showed there may be a greater reduction in rate of moderate-to-severe COPD exacerbations with triple therapy in participants with high-eosinophils (RR 0.67, 95% CI 0.60 to 0.75) compared to low-eosinophils (RR 0.87, 95% CI 0.81 to 0.93) (test for subgroup differences: P < 0.01) (high/low cut-offs: 150 eosinophils/µL in three studies; 200 eosinophils/µL in one study). However, moderate-to-substantial heterogeneity was observed in both high- and low-eosinophil subgroups. These subgroup analyses are observational by nature and thus results should be interpreted with caution. Triple therapy may be associated with reduced rates of severe COPD exacerbations (RR 0.75, 95% CI 0.67 to 0.84; n = 14,131; low-certainty evidence). Triple therapy improved health-related quality of life assessed using the St George's Respiratory Questionnaire (SGRQ) by the minimal clinically important difference (MCID) threshold (4-point decrease) (35.3% versus 42.4%, odds ratio (OR) 1.35, 95% CI 1.26 to 1.45; n = 14,070; high-certainty evidence). Triple therapy may result in fewer symptoms measured using the Transition Dyspnoea Index (TDI) (OR 1.33, 95% CI 1.13 to 1.57; n = 3044; moderate-certainty evidence) and improved lung function as measured by change in trough FEV1 (mean difference 38.68 mL, 95% CI 22.58 to 54.77; n = 11,352; low-certainty evidence). However, these benefits fell below MCID thresholds for TDI (1-unit decrease) and trough FEV1 (100 mL), respectively. Triple therapy is probably associated with a higher risk of pneumonia as a serious adverse event compared to combination LABA/LAMA inhalers (3.3% versus 1.9%, OR 1.74, 95% CI 1.39 to 2.18; n = 15,412; moderate-certainty evidence). In contrast, all-cause serious adverse events may be similar between groups (19.7% versus 19.7%, OR 0.95, 95% CI 0.87 to 1.03; n = 15,412; low-certainty evidence). All-cause mortality may be lower with triple therapy (1.4% versus 2.0%, OR 0.70, 95% CI 0.54 to 0.90; n = 15,397; low-certainty evidence).
AUTHORS' CONCLUSIONS
The available evidence suggests that triple therapy may reduce rates of COPD exacerbations (low-certainty evidence) and results in an improvement in health-related quality of life (high-certainty evidence) compared to combination LABA/LAMA inhalers, but probably confers an increased pneumonia risk as a serious adverse event (moderate-certainty evidence). Triple therapy probably improves respiratory symptoms and may improve lung function (moderate- and low-certainty evidence, respectively); however, these benefits do not appear to be clinically significant. Triple therapy may reduce the risk of all-cause mortality compared to combination LABA/LAMA inhalers (low-certainty evidence). The certainty of the evidence was downgraded most frequently for inconsistency or indirectness. Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies. We found limited data on the effects of triple therapy compared to combination LABA/LAMA inhalers in patients with mild-moderate COPD and those without a recent exacerbation history.
Topics: Humans; Female; Middle Aged; Aged; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Dyspnea; Pneumonia; Disease Progression
PubMed: 38054551
DOI: 10.1002/14651858.CD011600.pub3 -
The Journal of Arthroplasty Jun 2024Patients undergoing total joint arthroplasty (TJA) who report penicillin allergy (PA) are frequently administered second-line antibiotics, although recent evidence...
BACKGROUND
Patients undergoing total joint arthroplasty (TJA) who report penicillin allergy (PA) are frequently administered second-line antibiotics, although recent evidence suggests that this may be unnecessary and could increase infection risk. Many institutions have aimed to improve antibiotic deployment via allergy testing and screening; however, there is little standardization to this process. This review aimed to evaluate (1) antibiotic selection in patients who report PA and assess the impact of screening and testing interventions, (2) rates of allergic reactions in patients who report PA, and (3) the association between reported PA and screening or testing programs and odds of surgical site infection or periprosthetic joint infection.
METHODS
PubMed, EBSCOhost, and Google Scholar electronic databases were searched on February 4, 2023 to identify all studies published since January 1, 2000 that evaluated the impact of PA on patients undergoing TJA (PROSPERO study protocol registration: CRD42023394031). Articles were included if full-text manuscripts in English were available, and the study analyzed the impact of PA and related interventions on TJA patients. There were 11 studies evaluating 1,276,663 patients included. Interventions were compared via presentation of key findings regarding rates of clinically relevant or high-risk PA reported upon screenings or testings, cephalosporin utilizations, allergic reactions, and postoperative infections (surgical site infection and periprosthetic joint infection).
RESULTS
All 6 studies found that PA screening and testing markedly increase the use of first-line antibiotics. Testing showed low rates of true allergy (0.7 to 3%) and allergic reaction frequency for patients who have reported PA receiving cephalosporins was between 0% and 2%. Although there were mixed findings across studies, there was a trend toward second-line antibiotic prophylaxis being associated with a slightly higher rate of infection in PA patients.
CONCLUSIONS
Using PA screening and testing can promote antibiotic stewardship by safely increasing the use of first-line antibiotics in patients who have a reported PA.
LEVEL OF EVIDENCE
Level III, Therapeutic Study.
Topics: Humans; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimicrobial Stewardship; Arthroplasty, Replacement; Drug Hypersensitivity; Patient Safety; Penicillins; Prosthesis-Related Infections; Surgical Wound Infection
PubMed: 38040064
DOI: 10.1016/j.arth.2023.11.034 -
Allergy May 2024
Topics: Humans; Angioedemas, Hereditary; Clinical Trials as Topic; Treatment Outcome
PubMed: 38009479
DOI: 10.1111/all.15962 -
The Journal of Allergy and Clinical... Feb 2024There is currently no standardized duration of drug provocation test (DPT) for confirming/delabeling beta-lactam hypersensitivity reaction (BL-HSR). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is currently no standardized duration of drug provocation test (DPT) for confirming/delabeling beta-lactam hypersensitivity reaction (BL-HSR).
OBJECTIVES
This meta-analysis and systematic review aimed to investigate the added diagnostic value of extended-day over single-day DPT for confirming/delabeling BL-HSR in adults and children.
METHODS
The MEDLINE, EMBASE, Web of Science, and CINAHL online databases were searched from inception to March 15, 2023, for studies that performed extended-day DPT to confirm/delabel BL-HSR. Risk difference and risk ratio were used to compare the proportions of patients with confirmed BL-HSR by single-day or extended-day DPT.
RESULTS
A total of 10,371 DPTs from 42 studies were included. Extended-day DPTs ranged from 2 to 7 days, or as long as index reactions were reported (maximum 10 days). The overall prevalence of confirmed BL-HSR was 6.96% (3.31% during the first-day DPT, and 3.65% during extended-day DPT). Approximately half of the positive reactions during extended-day DPT occurred during the second/third day. The increased detected pool prevalence of confirmed BL-HSR yielded by extended-day DPT was 0.03 (95% CI, 0.02%-0.04%; I = 57.69%; P < .001), and the risk ratio of positive reactions between extended-day and single-day DPT was 1.94 (95% CI, 1.62-2.33; I = 36.26%; P < .001). The risk difference increased per 1% increase in prevalence of BL-HSR by 0.6% (95% CI, 0.4%-0.7%; P < .001). Twenty-three severe reactions occurred during DPT, and only 2 severe reactions (0.02%) occurred during extended-day DPT. An additional 28 extended-day DPTs were needed to identify 1 mild reaction.
CONCLUSIONS
The increased prevalence of confirmed BL-HSR observed during extended-day DPT could be attributed to the first-day DPT. As a result, our findings do not conclusively support the use of extended-day DPT over single-day DPT. Further studies, incorporating a washout period, are required to comprehensively compare these 2 approaches.
Topics: Child; Adult; Humans; beta-Lactams; Drug Hypersensitivity; Skin Tests; Thiones; Anti-Bacterial Agents
PubMed: 38000713
DOI: 10.1016/j.jaip.2023.11.028 -
Current Allergy and Asthma Reports Dec 2023To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients.
RECENT FINDINGS
Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.
Topics: Humans; Epistaxis; Tranexamic Acid; Timolol; Telangiectasia, Hereditary Hemorrhagic; Propranolol; Network Meta-Analysis; Tacrolimus; Estriol; Estradiol; Tamoxifen
PubMed: 37995018
DOI: 10.1007/s11882-023-01116-8