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Clinical Reviews in Allergy & Immunology Feb 2024Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially... (Review)
Review
Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.
Topics: Adult; Humans; Child; Drug Hypersensitivity Syndrome; Eosinophilia; Early Diagnosis
PubMed: 38466562
DOI: 10.1007/s12016-024-08983-7 -
Clinical Reviews in Allergy & Immunology Apr 2024Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin... (Meta-Analysis)
Meta-Analysis Review
Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions.
Topics: Humans; Drug Hypersensitivity; Penicillins; Skin Tests; Practice Guidelines as Topic; World Health Organization; Anti-Bacterial Agents
PubMed: 38696031
DOI: 10.1007/s12016-024-08988-2 -
Journal of Clinical Medicine Jul 2023Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and... (Review)
Review
Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney.
PubMed: 37510691
DOI: 10.3390/jcm12144576 -
Cureus Dec 2023Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination... (Review)
Review
Comparison of the Efficacy of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel in Improving Survival and Quality of Life in the Advanced Ovarian Cancer Patient Population: A Systematic Review and Meta-Analysis of Randomized Control Trials.
Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination regimens with paclitaxel plus platinum-based agents such as cisplatin/carboplatin and taxanes, have shown promising results for advanced ovarian cancer. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of two treatment regimens for advanced ovarian cancer: cisplatin/paclitaxel and carboplatin/paclitaxel. PubMed (Medline), Science Direct, and Cochrane Library were searched from inception to March 2023. The meta-analysis included patients with histologically verified International Federation of Gynaecology and Obstetrics (FIGO) stages IIB to IV ovarian carcinoma who received either carboplatin/paclitaxel or cisplatin/paclitaxel. The primary outcomes were progression-free survival (PFS), overall survival (OS), quality of life (QOL), complete response rate (CRR), and partial response rate (PRR). The revised Cochrane Risk of Bias Tool 2.0 was used to assess the quality of the RCTs The five RCTs chosen for this statistical analysis consisted of a total of 2239 participants, with 1109 receiving paclitaxel/cisplatin for treatment and the remaining 1130 receiving carboplatin/paclitaxel. Among all included outcomes, these reported significant findings: QoL (p-value=0.0002), thrombocytopenia (p=<0.00001), neurological toxicity (p-value=0.003), nausea/vomiting (p-value=<0.00001), myalgia/arthralgia (p-value=0.02), and febrile neutropenia (p-value=0.01). We concluded that the carboplatin/paclitaxel doublet endows a better quality of life (QOL) to patients along with significantly fewer gastrointestinal and neurological toxicities when compared with the cisplatin/paclitaxel combination. However, the myelosuppressive effects of carboplatin/paclitaxel remain a point of concern and may require clinical management.
PubMed: 38264391
DOI: 10.7759/cureus.51011 -
Journal of Dentistry Nov 2023To compare the clinical performance (retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative hypersensitivity) of self-adhesive... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the clinical performance (retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative hypersensitivity) of self-adhesive flowable composite resins (SAFCs) and flowable composite resins (FCs) in permanent teeth with occlusal cavities.
DATA
Randomized controlled trials (RCTs) of SAFCs versus FCs with a follow-up length of at least one year. No restrictions were placed on language or publication date.
SOURCES
Five databases, including PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials, were searched manually by browsing ten related journals. On 14 June 2023, all electronic and manual searches were updated.
STUDY SELECTION
Five RCTs with 138 participants were included. Cochrane's risk of bias tool (2.0) was implemented in selected studies, and the GRADE tool was utilised to evaluate the evidence quality. To summarize the effects of the treatments and pool the data, a random-effects model was used.
CONCLUSIONS
According to the modified United States Public Health Service Evaluation (USPHS) criteria, there was no discernible difference between the groups during the two-year follow-up period (maximum follow-up time). Nevertheless, FCs applied with the etch-and-rinse mode demonstrated superior marginal adaptation and marginal discoloration at the two-year follow-up (relative risk = 3.21 [1.50 to 6.83], 3.40 [1.10, 10.48]). The evidence for marginal discoloration at any recall time and marginal adaptation at the one-year follow-up was graded as moderate quality due to inconsistency. Moreover, low-quality evidence for marginal adaptation at two-year follow-up was due to imprecision and inconsistency.
CLINICAL SIGNIFICANCE
SAFCs exhibited clinical performance comparable to that of FCs in occlusal cavities. Further high-quality clinical trials are needed to provide solid evidence to support the clinical application of SAFCs.
REGISTRATION
PROSPERO (CRD42022374983).
Topics: Humans; Resin Cements; Dental Cements; Composite Resins; Dentition, Permanent; Dental Caries; Dental Marginal Adaptation; Dental Restoration, Permanent
PubMed: 37683798
DOI: 10.1016/j.jdent.2023.104691 -
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 Journal of Allergy and Clinical... Aug 2023The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated. (Meta-Analysis)
Meta-Analysis
Comparative Safety Profiles of Individual Second-Generation H1-Antihistamines for the Treatment of Chronic Urticaria: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated.
OBJECTIVE
To compare the safety profiles of individual sgAHs and/or dosing regimens in adolescents or adult patients with CU using a systematic review and network meta-analysis of all available evidence.
METHODS
With limited English publications, electronic databases and gray literature were searched for randomized clinical trials from inception, with searches last updated on January 20, 2023. Relevant safety outcomes included treatment unacceptability (all-cause discontinuation), tolerability (discontinuation due to any adverse events), adverse events, serious adverse events, central nervous system (CNS) side effects, and anticholinergic side effects. Regarding the network estimates, the probability of being associated with the highest adverse outcome risk was estimated for each treatment comparison.
RESULTS
Fifty-one randomized clinical trials with 14 individual sgAHs and different dosing regimens, involving 7502 participants, were included. On the basis of the findings from network meta-analyses, variations in sgAH treatment comparisons were observed regarding the unacceptability of treatment, tolerability, adverse events, and CNS side effects. There were no statistically significant differences between the results of sgAH treatment for serious adverse events and those for anticholinergic side effects. On the basis of the ranking of safety profiles, emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the top 3 ranked treatments with unfavorable safety profiles associated with CNS side effects and any adverse events.
CONCLUSIONS
These findings suggest evidence of variations in safety profiles among sgAHs for CU treatment, particularly in terms of adverse events and CNS side effects.
Topics: Adult; Humans; Adolescent; Network Meta-Analysis; Randomized Controlled Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Chronic Urticaria; Drug-Related Side Effects and Adverse Reactions; Cholinergic Antagonists
PubMed: 37088368
DOI: 10.1016/j.jaip.2023.03.058 -
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 -
European Respiratory Review : An... Dec 2023Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP.
METHODS
We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide ( ) % predicted) and arterial-alveolar oxygen gradient.
RESULTS
Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion ( % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I=0%). No serious trial-related adverse events were reported.
CONCLUSIONS
Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.
Topics: Humans; Pulmonary Alveolar Proteinosis; Granulocyte-Macrophage Colony-Stimulating Factor; Administration, Inhalation; Oxygen
PubMed: 37993127
DOI: 10.1183/16000617.0080-2023 -
Journal of Nephrology Sep 2023This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for... (Review)
Review
BACKGROUND
This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for culture-directed therapy of peritonitis, which would be especially useful in regions with a high prevalence of multidrug antibiotic-resistant strains.
METHODS
A literature search of Medline, Scopus, Embase and Google Scholar for articles published from inception to 25 January, 2023 was conducted. Only antibiotic stability studies conducted in vitro and not recently reviewed by So et al. were included. The main outcomes were chemical, physical, antimicrobial and microbial stability. This protocol was registered in PROSPERO (registration number CRD42023393366).
RESULTS
We screened 1254 abstracts, and 28 articles were included in the study. In addition to those discussed in a recent systematic review (So et al., Clin Kidney J 15(6):1071-1078, 2022), we identified 18 antimicrobial agents. Of these, 9 have intraperitoneal dosing recommendations in the recent International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines, and 7 of the 9 had stability data applicable to clinical practice. They were cefotaxime, ceftriaxone, daptomycin, ofloxacin, and teicoplanin in glucose-based solutions, tobramycin in Extraneal solution only and fosfomycin in Extraneal, Nutrineal, Physioneal 1.36% and 2.27% glucose solutions.
CONCLUSIONS
Physicochemical stability has not been demonstrated for all antibiotics with intraperitoneal dosing recommendations in the ISPD peritonitis guidelines. Further studies are required to determine the stability of antibiotics, especially in icodextrin-based and low-glucose degradation products, pH-neutral solutions.
Topics: Humans; Anti-Bacterial Agents; Dialysis Solutions; Glucose; Icodextrin; Peritoneal Dialysis; Peritonitis
PubMed: 37548827
DOI: 10.1007/s40620-023-01716-7